camptothecin

Research Excerpts

Overview

Camptothecin (CPT) is an anti-tumor natural product that forms a ternary complex with topoisomerase I (top I) and DNA. It is a naturally occurring alkaloid obtained from the stem wood of the Chinese tree, Camptotheca acuminata.

Excerpt	Reference	Relevance
"Homocamptothecin (hCPT) is an E-ring modified camptothecin (CPT) analogue bearing a methylene spacer between the alcohol and carboxyl functions of the CPT lactone. "	( Topoisomerase I-mediated antiproliferative activity of enantiomerically pure fluorinated homocamptothecins. Bailly, C; Baroggi, N; Bigg, DC; Camara, J; Cazaux, JB; Coulomb, H; Demarquay, D; Huchet, M; Lanco, C; Lavergne, O; Le Breton, C; Manginot, E; Muller, N; Rolland, A, 2000)	1.08
"Camptothecin (CPT) is an anti-tumor natural product that forms a ternary complex with topoisomerase I (top I) and DNA (CPT-top I-DNA). "	( Camptothecin (CPT) directly binds to human heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) and inhibits the hnRNP A1/topoisomerase I interaction. Kamisuki, S; Kanai, Y; Kusayanagi, T; Manita, D; Matsumoto, Y; Sakaguchi, K; Sugawara, F; Takada, K; Takakusagi, K; Takakusagi, Y; Toba, Y; Tsukuda, S, 2011)	3.25
"Camptothecin is a naturally occurring alkaloid that inhibits the DNA-replicating enzyme topoisomerase I."	( Camptothecin analogs in malignant gliomas: comparative analysis and characterization. Alderson, LM; Amundson, E; Brem, H; Colvin, M; Sampath, P; Tyler, BM; Wall, ME; Wani, MC; Weingart, JD, 2003)	2.48
"Camptothecin (CPT) is an example of this type of drug."	( Treatment of HT29 Human Colorectal Cancer Cell Line with Nanocarrier-Encapsulated Camptothecin Reveals Histone Modifier Genes in the Alsrhani, A; Farhana, A; Koh, AE; Kothandan, S; Mok, PL; Subbiah, SK, 2021)	1.57
"Camptothecin (CPT) is a potent broad-spectrum antitumor agent with efficient therapeutic effect for various cancers. "	( Glioma-targeted multifunctional nanoparticles to co-deliver camptothecin and curcumin for enhanced chemo-immunotherapy. Chen, M; Wang, X; Wang, Z; Yu, H, 2022)	2.41
"Camptothecin (CPT) is a potent anticancer agent for the treatment of colorectal cancer; however, it exhibits some limitations, including poor solubility, low stability, and low bioavailability via oral administration, which restrict its usability in clinical treatments. "	( A silica-based antioxidant nanoparticle for oral delivery of Camptothecin which reduces intestinal side effects while improving drug efficacy for colon cancer treatment. Li, N; Nagasaki, Y; Nguyen-Trinh, QN; Trinh, KXT; Trinh, NT; Vo, VT; Vong, LB, 2022)	2.41
"Camptothecin is a naturally occurring alkaloid obtained from the stem wood of the Chinese tree, Camptotheca acuminata. "	( Synthesis and Antitumor Evaluation of Glutathione Responsive Self-Immolative Disulphide Linked Camptothecin-Biotin Conjugate. Dhiman, S; Kaur, A; Lee, HB; Sharma, M, 2022)	2.38
"Camptothecin (CPT) is a monoterpenoid-alkaloid, an anticancer compound from plant. "	( Biotechnology for micropropagation and camptothecin production in Ophiorrhiza sp. Dey, A; Dwivedi, P; Gangaprasad, A; Ghorai, M; Kant, N; Konjengbam, M; Pandey, DK; Roy, D, 2022)	2.43
"Camptothecin (CPT) is an anticancer pentacyclic quinoline alkaloid widely used to treat cancer patients worldwide. "	( OpNAC1 transcription factor regulates the biosynthesis of the anticancer drug camptothecin by targeting loganic acid O-methyltransferase in Ophiorrhiza pumila. Cai, Y; Hao, X; Kai, G; Maoz, I; Ruan, Q; Wang, C; Wang, J; Wang, Y; Xiao, C; Xie, C; Yang, Y; Zhang, X; Zhou, W, 2023)	2.58
"Camptothecin (CPT) is a potent chemotherapeutic agent for various cancers, but the broader application of CPT is still hindered by its poor bioavailability and systemic toxicity. "	( Glutathione-Responsive Nanoparticles of Camptothecin Prodrug for Cancer Therapy. Gao, Y; Han, H; Liu, C; Lu, Y; Shang, K; Tang, L; Xie, J; Yu, C; Zhang, L; Zhu, L, 2023)	2.62
"Camptothecin (CPT) is a cytotoxic quinolone alkaloid (isolated from a traditional Chinese medicine Camptotheca acuminata), used for the treatment of various malignancies, which inhibits DNA topoisomerase I (Topo I). "	( Camptothecin-Loaded and Manganese Dioxide-Coated Polydopamine Nanomedicine Used for Magnetic Resonance Imaging Diagnosis and Chemo-Photothermal Therapy for Lung Cancer. Chen, Y; Jia, L; Su, M; Zhang, Z, 2022)	3.61
"Camptothecin is a naturally occurred anticancer drug but exhibits limitations including poor aqueous solubility, low bioavailability, and high level of adverse drug reactions on normal organs. "	( Novel amphiphilic hydroxyethyl starch-based nanoparticles loading camptothecin exhibit high anticancer activity in HepG2 cells and zebrafish. Chen, X; Li, P; Liu, X; Qin, D; Sheng, W; Wang, F; Wang, L; Zhang, C, 2023)	2.59
"Camptothecin (CPT) is an attractive natural drug for cancer chemotherapy. "	( Development of a novel sialic acid-conjugated camptothecin prodrug for enhanced cancer chemotherapy. Dong, H; Huang, X; Wu, X, 2023)	2.61
"Camptothecin is an important anticancer alkaloid produced by particular plant species. "	( Genomic and transcriptomic analysis of camptothecin producing novel fungal endophyte: Alternaria burnsii NCIM 1409. Natarajan, S; Pucker, B; Srivastava, S, 2023)	2.62
"Camptothecin (CPT) is an anticancer drug, and is not employed in the clinic because of its high hydrophobicity and low active form stability. "	( Camptothecin: solubility, in-vitro drug release, and effect on human red blood cells and sperm cold preservation. Fatmi, S; Iguer-Ouada, M; Skiba, M; Taouzinet, L, )	3.02
"Camptothecin (CPT) is a cytotoxic alkaloid that attenuates the replication of cancer cells "	( Camptothecin-based prodrug nanomedicines for cancer therapy. Guo, Z; Jiang, H; Wang, C; Yu, J; Zhang, R, 2023)	3.8
"Camptothecin is a high-value anti-cancerous compound produced in many taxonomically unrelated species. "	( Molecular characterization and overexpression analyses of secologanin synthase to understand the regulation of camptothecin biosynthesis in Nothapodytes nimmoniana (Graham.) Mabb. Kaul, V; Kumar, A; Lattoo, SK; Misra, P; Rather, GA; Sharma, A, 2020)	2.21
"Camptothecin (CPT) is a highly cytotoxic chemotherapeutic compound, yet poorly water-soluble and non-specific."	( Targeted camptothecin delivery via silicon nanoparticles reduces breast cancer metastasis. Cifuentes-Rius, A; Howard, CB; Hutmacher, DW; Janowicz, PW; Kaur, I; Lahr, CA; Landgraf, M; McGovern, JA; Ravichandran, A; Sanchez-Herrero, A; Shafiee, A; Voelcker, NH, 2020)	1.7
"Camptothecin (CPT) is a DNA Topoisomerase I inhibitor and exerts a broad-spectrum anticancer profile."	( Triple stimuli-responsive supramolecular nanoassembly with mitochondrial targetability for chemophotothermal therapy. Cheng, Y; Ji, Y; Tong, J, 2020)	1.28
"Camptothecin (CPT) is a cytotoxic quinoline alkaloid isolated from the bark and branches of the Chinese tree "	( Therapeutic Mechanism and Effect of Camptothecin on Dextran Sodium Sulfate-Induced Ulcerative Colitis in Mice. Chen, T; Jiang, Y; Li, G; Liu, K; Qi, Z; Wang, Y; Xiao, H; Yu, W, 2021)	2.34
"Camptothecin (CPT) is a bioactive secondary metabolite of the woody plant Camptotheca acuminata, which has shown high toxicity to various pests."	( Growth inhibition of Spodoptera frugiperda larvae by camptothecin correlates with alteration of the structures and gene expression profiles of the midgut. Cao, L; Li, X; Lin, J; Shu, B; Yu, H; Zhang, W; Zou, Y, 2021)	1.59
"Camptothecin (CPT) is an inhibitor of DNA topoisomerase-I with several anticancer properties but has poor solubility and a high degradation rate."	( Enhanced cytotoxic effect of camptothecin nanosponges in anaplastic thyroid cancer cells in vitro and in vivo on orthotopic xenograft tumors. Annaratone, L; Argenziano, M; Barrera, G; Boggio, E; Boldorini, R; Cavalli, R; Chiocchetti, A; Clemente, N; Dianzani, C; Dianzani, U; Fantozzi, R; Ferrara, B; Gigliotti, CL; Giovarelli, M; Marchiò, C; Occhipinti, S; Pizzimenti, S; Trotta, F, 2017)	1.47
"Camptothecin (CPT) is an anti-cancer drug that effectively treats various cancers, including colon cancer. "	( Efficiency of newly formulated camptothecin with β-cyclodextrin-EDTA-Fe Alarfaj, AA; Amira, F; Arulselvan, P; Arumugam, R; Benelli, G; Danjuma, L; Fakurazi, S; Hamat, RA; Higuchi, A; Krishnan, P; Kumar, SS; Kumari, S; Munusamy, MA; Murugan, K; Pooi Ling, M; Priya, SP; Rajan, M; Sakinah, S, 2017)	2.18
"Camptothecin is a novel NRF2 inhibitor that may be repurposed in combination with other chemotherapeutics to enhance their efficacy in treating high NRF2-expressing cancers."	( Camptothecin suppresses NRF2-ARE activity and sensitises hepatocellular carcinoma cells to anticancer drugs. Bud Nelson, M; Chen, F; Feng, B; Pi, J; Qu, W; Wang, H; Xue, P; Zhang, Q; Zhao, R; Zhu, J, 2017)	3.34
"Camptothecin (CPT) is a potent drug against cancers, originally from plants. "	( Characterization and antitumor activity of camptothecin from endophytic fungus Li, S; Ran, X; Wang, J; Zhang, G, 2017)	2.16
"Camptothecin (CPT) is a broad spectrum anticancer drug, but its application is limited due to the poor water solubility, lactone ring instability, and low drug loading potential. "	( Dimeric camptothecin-loaded RGD-modified targeted cationic polypeptide-based micelles with high drug loading capacity and redox-responsive drug release capability. Chen, M; Chen, X; Guo, Z; Tian, H; Xu, M; Zhou, X, 2017)	2.33
"Camptothecin (CPT) is a cytotoxic quinoline alkaloid that is used clinically as an anticancer drug. "	( Antitumor potential of a novel camptothecin derivative, ZBH-ZM-06. Bao, WG; Li, YQ; Shi, WG; Tu, ZK; Wu, D; Yin, QL; Yu, H; Yu, YY; Zhao, DW; Zhong, BH, 2018)	2.21
"Camptothecin (CPT) is an important topoisomerase I enzyme (Topo I) targeting anti-cancer drug, but its oral administration is limited by poor bioavailability and severe side effects. "	( Redox sensitive lipid-camptothecin conjugate encapsulated solid lipid nanoparticles for oral delivery. Du, Y; He, W; Ismail, M; Li, X; Ling, L; Xia, Q; Yao, C; Zhou, W, 2018)	2.24
"Camptothecin (CPT) is a well-known anticancer drug, which causes cancer cell apoptosis via the induction of DNA damage; however, the cytotoxicity of CPT easily reaches a plateau at a relatively high dose in lung cancer cells, thus limiting its efficacy."	( Human non‑small cell lung cancer cells can be sensitized to camptothecin by modulating autophagy. Chen, BH; Chen, JY; Chiu, CC; Chiu, YH; Hsu, HW; Hsu, SH; Huang, KC; Huang, WP; Liu, W; Wu, CY, 2018)	1.44
"Camptothecin (CMT) is an anti-tumour alkaloid drug exhibiting selective topoisomerase-I inhibitory activity by eventually hindering dynamic functions of DNA duplex via initiating apoptosis. "	( Photophysical and thermodynamic evaluation on the in vitro and in silico binding profile of Camptothecin with DNA. Sudarsanakumar, C; Sukumaran, S; Thomas, RK, 2019)	2.18
"Camptothecin (CPT) is a popular therapeutic agent that targets topoisomerase I. "	( Camptothecin induces mitotic arrest through Mad2-Cdc20 complex by activating the JNK-mediated Sp1 pathway. Choi, YH; Dilshara, MG; Jayasooriya, RGPT; Karunarathne, WAHM; Kim, GY, 2019)	3.4
"Camptothecin (CAM) is a well-known, complex, plant-derived antitumor monoterpenoid indole alkaloid (MIA). "	( Bifunctional Cytochrome P450 Enzymes Involved in Camptothecin Biosynthesis. Jiang, L; Li, W; Luo, Y; Pang, J; Pu, X; Qu, X; Yang, Y; Zhang, G, 2019)	2.21
"Camptothecin (CPT) is a topoisomerase IB (TopIB) selective inhibitor whose derivatives are currently used in cancer therapy. "	( Role of the protein in the DNA sequence specificity of the cleavage site stabilized by the camptothecin topoisomerase IB inhibitor: a metadynamics study. Coletta, A; Desideri, A, 2013)	2.05
"Camptothecin is a plant alkaloid that specifically binds topoisomerase I, inhibiting its activity and inducing double stranded breaks in DNA and activating the cell responses to DNA damage."	( Identification of a type I Ca2+/Mg2+-dependent endonuclease induced in maize cells exposed to camptothecin. Sánchez-Pons, N; Vicient, CM, 2013)	2.05
"Camptothecin (CPT, 1) is a potent anticancer natural product which led to the discovery of two clinically used anticancer drugs topotecan and irinotecan. "	( Dysoxylum binectariferum bark as a new source of anticancer drug camptothecin: bioactivity-guided isolation and LCMS-based quantification. Bharate, SB; Gupta, AP; Jaglan, S; Jain, SK; Kushwaha, M; Meena, S; Uma Shaanker, R; Vishwakarma, RA, 2014)	2.08
"Camptothecin (CPT) is an effective anticancer agent against various cancers but the clinical application is limited because of its poor water solubility, low bioavailability and severe toxic side effects. "	( Preparation of camptothecin-loaded targeting nanoparticles and their antitumor effects on hepatocellular carcinoma cell line H22. Liu, Z; Xiong, X; Yan, B; Yang, A; Zhou, M, 2016)	2.23
"Camptothecin (CPT) is a quinolone alkaloid that induces cytotoxicity in a variety of cancer cell lines."	( Camptothecin sensitizes human hepatoma Hep3B cells to TRAIL-mediated apoptosis via ROS-dependent death receptor 5 upregulation with the involvement of MAPKs. Choi, YH; Hyun, JW; Jayasooriya, RG; Kim, GY, 2014)	2.57
"Camptothecin (CPT) is a potent antitumor agent and functions via inhibiting the activity of topoisomerase I during DNA replication. "	( The self-assembling camptothecin-tocopherol prodrug: An effective approach for formulating camptothecin. Ghazwani, M; Huang, Y; Li, S; Liu, C; Lu, J; Ma, X; Wang, P; Xu, J; Zhang, P, 2015)	2.18
"Camptothecin is an anti-cancer drug extracted from Camptotheca acuminata, a tree native to mainland China. "	( Camptothecin and topotecan inhibit adipocyte differentiation by inducing degradation of PPARγ. Jeong, M; Kim, JH; Lee, SS; Song, J, 2015)	3.3
"Camptothecin is a monoterpene indole alkaloid (MIA) used to produce semisynthetic antitumor drugs. "	( Metabolite Diversity in Alkaloid Biosynthesis: A Multilane (Diastereomer) Highway for Camptothecin Synthesis in Camptotheca acuminata. DellaPenna, D; Jones, AD; Magallanes-Lundback, M; Mesberg, A; Pradhan, S; Sadre, R; Salim, V, 2016)	2.1
"Camptothecin is a quinoline alkaloid, isolated from the Chinese tree Camptotheca acuminate which exhibits its cytotoxic activity by the inhibition of nuclear enzyme Topoisomerase I (topo I). "	( Discovery of Camptothecin Based Topoisomerase I Inhibitors: Identification Using an Atom Based 3D-QSAR, Pharmacophore Modeling, Virtual Screening and Molecular Docking Approach. Dev, S; Dhaneshwar, SR; Mathew, B, 2016)	2.25
"Camptothecin (CPT) is a natural product discovered to be active against various cancers through its ability to inhibit Topoisomerase I (TOP1). "	( An analog of camptothecin inactive against Topoisomerase I is broadly neutralizing of HIV-1 through inhibition of Vif-dependent APOBEC3G degradation. Bennett, RP; Buckheit, RW; Hartman, TL; Hogan, PA; Mankowski, MK; Morales, GA; Ptak, RG; Salter, JD; Smith, HC; Snyder, BA; Stewart, RA, 2016)	2.25
"Camptothecin (CPT) is a potent chemotherapeutic agent that shows a broad spectrum of anticancer activities. "	( Enhanced anticancer activity of drug nanoparticles formulated with β-cyclodextrin. Jagtiani, T; Liang, JF; Zhan, H, 2017)	1.9
"Camptothecin is a topoisomerase I inhibitor that acts against a broad spectrum of cancers. "	( Acoustically active perfluorocarbon nanoemulsions as drug delivery carriers for camptothecin: drug release and cytotoxicity against cancer cells. Fang, JY; Hua, SC; Hung, CF; Hwang, TL, 2009)	2.02
"Camptothecin is an anticancer drug that acts against a broad spectrum of tumors. "	( Development and evaluation of lipid nanoparticles for camptothecin delivery: a comparison of solid lipid nanoparticles, nanostructured lipid carriers, and lipid emulsion. Fang, JY; Hua, SC; Huang, ZR; Yang, YL, 2008)	2.04
"Camptothecin (CPT) is a potent anticancer agent. "	( Comparative evaluation of polymeric and amphiphilic cyclodextrin nanoparticles for effective camptothecin delivery. Bilensoy, E; Caliş, S; Cirpanli, Y; Lale Doğan, A, 2009)	2.02
"Camptothecin is a plant alkaloid derived from the Chinese tree Camptotheca acuminate."	( Recent development in nano-sized dosage forms of plant alkaloid camptothecin-derived drugs. Cuong, NV; Hsieh, MF; Huang, CM, 2009)	1.31
"Camptothecin is a naturally occurring, pentacyclic quinoline alkaloid that possesses high cytotoxic activity in a variety of cell lines."	( Cancer therapies utilizing the camptothecins: a review of the in vivo literature. Simanek, EE; Venditto, VJ, 2010)	1.37
"Camptothecin (CPT) is a topoisomerase I inhibitor, derivatives of which are being used for cancer chemotherapy. "	( Transcription-dependent activation of ataxia telangiectasia mutated prevents DNA-dependent protein kinase-mediated cell death in response to topoisomerase I poison. Sakasai, R; Takagi, M; Teraoka, H; Tibbetts, RS, 2010)	1.8
"Camptothecin (CPT) is a cytotoxic quinoline alkaloid endowed with the inhibition of topoisomerase I, an essential enzyme for the normal functioning of DNA. "	( Electrochemical reduction mechanism of camptothecin at glassy carbon electrode. Diculescu, VC; Oliveira-Brett, AM; Qureshi, R; Shah, A, 2010)	2.07
"Camptothecin is a reported inhibitor of HIF-1alpha translation, while mitomycin C has been reported to induce p53-dependent HIF-1alpha degradation."	( Inhibition of hypoxia-inducible factor-1alpha (HIF-1alpha) protein synthesis by DNA damage inducing agents. Bushell, M; Chew, EH; Chua, YL; Gao, J; Hagen, T; Lou, JJ, 2010)	1.08
"Camptothecin is a selective inhibitor of DNA topoisomerase I, and has effective antitumor activity. "	( Dissecting the transcriptional functions of human DNA topoisomerase I by selective inhibitors: implications for physiological and therapeutic modulation of enzyme activity. Baranello, L; Capranico, G; Marinello, J, 2010)	1.8
"Camptothecin (CPT) is an essential precursor of semisynthetic chemotherapeutic agents for cancers throughout the world. "	( Correlation of camptothecin-producing ability and phylogenetic relationship in the genus Ophiorrhiza. Chayamarit, K; Chuanasa, T; Denduangboripant, J; Saito, K; Sukrong, S; Viraporn, V; Yamazaki, M, 2011)	2.16
"The camptothecins are a prime example as they represent a diverse class of approved anticancer drugs and drug candidates whose charge distribution varies with pH."	( Tumor physiology and charge dynamics of anticancer drugs: implications for camptothecin-based drug development. Adams, DJ; Morgan, LR, 2011)	1.08
"Camptothecin (CPT) is a potent broad-spectrum anticancer agent that acts through inhibition of topoisomerase 1. "	( Preclinical to clinical development of the novel camptothecin nanopharmaceutical CRLX101. Eliasof, S; Hwang, J; Ryan, J; Svenson, S; Wolfgang, M, 2011)	2.07
"Camptothecin is a plant alkaloid that specifically binds topoisomerase I, inhibiting its activity and inducing double stranded breaks in DNA, activating the cell responses to DNA damage and, in response to severe treatments, triggering cell death."	( Transcriptomic and proteomic profiling of maize embryos exposed to camptothecin. García-Muniz, N; Irar, S; Sánchez-Pons, N; Vicient, CM, 2011)	2.05
"Camptothecin (CPT) is a potent, broad spectrum antitumor agent that inhibits the activity of DNA topoisomerase I. "	( Preparation and antitumor study of camptothecin nanocrystals. Hollis, CP; Li, T; Zhang, H; Zhang, Q, 2011)	2.09
"Homocamptothecin (hCPT) is a camptothecin (CPT) homologue with the insertion of a methylene (CH₂) spacer between the alcohol moiety and carbonyl group of the classical six-membered α-hydroxylactone ring. "	( Synthesis and biological evaluation of novel homocamptothecins conjugating with dihydropyrimidine derivatives as potent topoisomerase I inhibitors. Cheng, P; Dong, G; Guo, W; Lei, N; Liu, W; Miao, Z; Sheng, C; Wang, S; Yao, J; Zhang, W; Zhang, Y; Zhu, L; Zhuang, C, 2011)	1.18
"Camptothecin (CPT) is an effective chemotherapeutic agent for treatment of patients with cancer. "	( Camptothecin induces apoptosis in cancer cells via microRNA-125b-mediated mitochondrial pathways. Chen, YQ; Feng, SY; Lin, KY; Ye, H; Zeng, CW; Zhang, H; Zhang, XJ, 2012)	3.26
"Camptothecins are a family of alkaloids originally extracted from the Chinese tree Camptotheca acuminata, Nyssaceae, exhibiting a strong activity against colorectal cancer (CRC). "	( Delivery methods of camptothecin and its hydrosoluble analogue irinotecan for treatment of colorectal cancer. Cacciatore, I; Cornacchia, C; Feliciani, F; Mollica, A; Pinnen, F; Stefanucci, A, 2012)	2.15
"Camptothecin is a monoterpenoid indole alkaloid that exhibits anti-tumor activity. "	( Suppression of camptothecin biosynthetic genes results in metabolic modification of secondary products in hairy roots of Ophiorrhiza pumila. Aoki, K; Asano, T; Iijima, Y; Kashihara, E; Kobayashi, K; Saito, K; Sasaki, R; Shibata, D; Sudo, H; Yamazaki, M, 2013)	2.19
"Homocamptothecin (hCPT) is a camptothecin (CPT) derivative with a seven-membered β-hydroxylactone E ring, which shows higher lactone stability and improves topoisomerase I (Topo I) inhibition activity. "	( Synthesis and biological evaluation of 7-alkenyl homocamptothecins as potent topoisomerase I inhibitors. Cheng, P; Dong, G; Guo, W; Lei, N; Liu, W; Miao, Z; Sheng, C; Yao, J; Zhang, W; Zhang, X; Zhu, L; Zhuang, C, 2012)	1.19
"Camptothecin (CPT) is a potent DNA Topoisomerase I inhibitor with anti-tumor activity in hematological and solid tumors. "	( Nanosponge-encapsulated camptothecin exerts anti-tumor activity in human prostate cancer cells. Barrera, G; Cavalli, R; Ciamporcero, E; Dianzani, C; Ellis, L; Fantozzi, R; Minelli, R; Pettazzoni, P; Pili, R; Trotta, F, 2012)	2.13
"Camptothecin (CPT) is an anticancer agent that kills cells by converting DNA topoisomerase I into a DNA-damaging agent. "	( Enhancing the anticancer efficacy of camptothecin using biotinylated poly(ethylene glycol) conjugates in sensitive and multidrug-resistant human ovarian carcinoma cells. Lalloo, A; Minko, T; Paranjpe, PV; Qiu, B; Sinko, PJ; Stein, S; Won, R, 2002)	2.03
"Camptothecin (CPT) is an anticancer and antiviral alkaloid produced by the Chinese tree Camptotheca acuminata (Nyssaceae) and some other species belonging to the families Apocynaceae, Olacaceae, and Rubiaceae. "	( Camptothecin and 10-hydroxycamptothecin from Camptotheca acuminata hairy roots. Lorence, A; Medina-Bolivar, F; Nessler, CL, 2004)	3.21
"Camptothecins (CPTs) are a relatively new family of compounds that specifically target topoisomerase I (Top1)."	( Mechanisms of resistance to topoisomerase I-targeting drugs. Rasheed, ZA; Rubin, EH, 2003)	1.04
"Camptothecin is an example of a potent drug with a short half-life that would benefit from a localized drug depot system that maintains its stability prior to being released. "	( A biodegradable injectable thermoplastic for localized camptothecin delivery. Amsden, B; Hatefi, A; Knight, D, 2004)	2.01
"Homocamptothecin is a lead compound for inhibiting Top1, and is composed of five conjugated planar rings (A-E)."	( Analysis of human topoisomerase I inhibition and interaction with the cleavage site +1 deoxyguanosine, via in vitro experiments and molecular modeling studies. Burke, TG; Curran, DP; Du, W; Jerina, DM; Kohlhagen, G; Laco, GS; Pommier, Y; Sayer, JM, 2004)	0.8
"Camptothecin (CPT) is an anticancer drug that promotes DNA breakage at replication forks and the formation of lesions that activate the processes of homologous recombination (HR) and nonhomologous end joining. "	( Camptothecin enhances the frequency of oligonucleotide-directed gene repair in mammalian cells by inducing DNA damage and activating homologous recombination. Ferrara, L; Kmiec, EB, 2004)	3.21
"Camptothecin (CPT) is a modified monoterpene indole alkaloid produced by Camptotheca acuminata (Nyssaceae), Nothapodytes foetida, Pyrenacantha klaineana, Merrilliodendron megacarpum (Icacinaceae), Ophiorrhiza pumila (Rubiaceae), Ervatamia heyneana (Apocynaceae) and Mostuea brunonis (Gelsemiaceae), species belonging to unrelated orders of angiosperms. "	( Camptothecin, over four decades of surprising findings. Lorence, A; Nessler, CL, 2004)	3.21
"Camptothecins are a class of antineoplastic agents that function via inhibition of topoisomerase I, a critical enzyme involved in DNA replication, transcription and chromosomal structure. "	( Topoisomerases in the treatment of metastatic or recurrent squamous carcinoma of the head and neck. Murphy, BA, 2005)	1.77
"Camptothecin (CPT), known to be an effective anticancer drug, has a limited therapeutic utility because of its poor water solubility. "	( SDS-aided immobilization and controlled release of camptothecin from agarose hydrogel. Li, L; Liu, J, 2005)	2.02
"Camptothecin is an anticancer quinoline alkaloid effective against colon cancer. "	( Comparative studies on the camptothecin content from Nothapodytes foetida and Ophiorrhiza species. Roja, G, 2006)	2.07
"Camptothecin (CPT) is a potent inhibitor of DNA topoisomerase I with a wide spectrum of anti-tumor activity. "	( Analysis of common gene expression patterns in four human tumor cell lines exposed to camptothecin using cDNA microarray: identification of topoisomerase-mediated DNA damage response pathways. Fu, X; Guo, X; Li, Y; Lu, Y; Mao, Y; Rui, Y; Wei, Q; Xie, Y; Yin, G; Ying, K; Zhang, J, 2006)	2
"Camptothecin is a strong anti-tumor compound isolated from Camptotheca acuminata. "	( [Effects of cu2+ on biosynthesis of camptothecin in cell cultures of Camptotheca acuminata]. Gu, Q; Song, DF; Zhang, H; Zhu, MY, 2006)	2.05
"Camptothecin (CPT) is a topoisomerase I inhibitor that acts against a broad spectrum of cancers. "	( Camptothecin in sterically stabilized phospholipid nano-micelles: a novel solvent pH change solubilization method. Koo, OM; Onyuksel, H; Rubinstein, I, )	3.02
"Camptothecin (CPT) is a well-established topoisomerase I inhibitor against a broad spectrum of cancers. "	( Camptothecin in sterically stabilized phospholipid micelles: a novel nanomedicine. Koo, OM; Onyuksel, H; Rubinstein, I, 2005)	3.21
"Camptothecin is a potent anticancer agent producing well-characterized replication-mediated DNA double-strand breaks through the collision of replication forks with topoisomerase I cleavage complexes."	( The intra-S-phase checkpoint affects both DNA replication initiation and elongation: single-cell and -DNA fiber analyses. Aladjem, MI; Conti, C; Pommier, Y; Seiler, JA; Syed, A, 2007)	1.06
"Camptothecin (CPT) is a hydrophobic antitumor drug. "	( Diffusion of camptothecin immobilized with cationic surfactant into agarose hydrogel containing anionic carrageenan. Li, L; Liu, J, 2007)	2.15
"Camptothecin (CPT) is a naturally occurring alkaloid that shows promise in antitumor activity in vitro against various tumor cell lines. "	( A novel polyrotaxane-based intracellular delivery system for camptothecin: in vitro feasibility evaluation. Chang, LC; Kwon, YM; Lee, WK; Moon, C; Park, YJ; Yang, VC, 2008)	2.03
"Camptothecin (CPT) is an alkaloid that displays considerable antitumour activity, but clinical use has been limited by its poor water solubility and the instability of the lactone moiety (active form) in physiological media. "	( Stealth and non-stealth nanocapsules containing camptothecin: in-vitro and in-vivo activity on B16-F10 melanoma. Alvarez Silva, M; Fernandes, D; Hangai, M; Lemos-Senna, E; Loch-Neckel, G; Nemen, D; Puhl, AC; Santos Silva, MC; Stimamiglio, MA, 2007)	2.04
"Camptothecin (CPT) is an anticancer drug that inhibits topoisomerase I (Topo I) by forming a ternary DNA-CPT-Topo I complex. "	( Photochemical properties of camptothecin in the presence of copper(II) ions: the role of radicals as prospective species in photodynamic therapy. Breza, M; Brezová, V; Dvoranová, D; Mazúr, M; Valko, M; Zúbor, V, 2007)	2.08
"Camptothecin (CPT) is an anti-cancer drug with low solubility in aqueous solutions, which limits its efficacy during chemotherapy. "	( Efficacy of camptothecin and polymer-conjugated camptothecin in tumor spheroids and solid tumors. Haverstick, K; Page, RL; Saltzman, WM; Ying, V, 2007)	2.16
"Homocamptothecins (hCPTs) are a novel class of topoisomerase I (Top1) inhibitors with enhanced chemical stability compared with the currently used camptothecin (CPT) analogs irinotecan and topotecan. "	( Reduced expression of DNA topoisomerase I in SF295 human glioblastoma cells selected for resistance to homocamptothecin and diflomotecan. Bates, SE; Guirouilh-Barbat, J; Liao, Z; Polgar, O; Pommier, Y; Robey, RW; To, KK, 2008)	1.12
"Camptothecin is a topoisomerase I inhibitor with definite anti-psoriatic effect. "	( Effects of isocamptothecin, a novel camptothecin analogue, on proliferation, apoptosis and telomerase activity in HaCaT cells. An, L; Bao, Y; Hou, S; Lin, J; Lin, X; Liu, X, 2008)	2.15
"Camptothecin (CPT) is a strong antitumor agent, but its use limited by its low solubility and the instability of the active lactone form. "	( In vivo antitumor activity of camptothecin incorporated in liposomes formulated with an artificial lipid and human serum albumin. Hattori, Y; Kawano, K; Maitani, Y; Toma, K; Watanabe, M, 2008)	2.08
"Camptothecin is a natural product derived from the Oriental tree Camptotheca acuminata which has shown activity in a number of experimental tumors. "	( Camptothecin analogues in the treatment of non-small cell lung cancer. Ardizzoni, A, 1995)	3.18
"Camptothecin is a potent antineoplastic agent that interferes with the action of eukaryotic DNA topoisomerase I; the covalent enzyme-DNA intermediate is reversibly stabilized, leading to G2 arrest and cell death. "	( SCT1 mutants suppress the camptothecin sensitivity of yeast cells expressing wild-type DNA topoisomerase I. Bjornsti, MA; Kauh, EA, 1995)	2.03
"Camptothecin-11 (CPT-11) is a new derivative of camptothecin, a plant alkaloid antitumor agent. "	( Determinants of drug response in camptothecin-11-resistant glioma cell lines. Fujiwara, T; Matsumoto, Y; Nagao, S, 1995)	2.02
"Camptothecin is an established antitumor drug and a well-characterized inhibitor of eukaryotic DNA topoisomerase I."	( Molecular and cytotoxic effects of camptothecin, a topoisomerase I inhibitor, on trypanosomes and Leishmania. Bodley, AL; Shapiro, TA, 1995)	1.29
"Camptothecin is an anticancer and anti-viral alkaloid produced by the Chinese tree Camptotheca acuminata (Nyssaceae). "	( Sites of accumulation of the antitumor alkaloid camptothecin in Camptotheca acuminata. López-Meyer, M; McKnight, TD; Nessler, CL, 1994)	1.99
"Camptothecin-11 (CPT-11) is a new derivation of camptothecin, a plant alkaloid antitumor agent. "	( [Quantitative analysis of DNA topoisomerase I activity in human and rat glioma: characterization and mechanism of resistance to antitopoisomerase chemical, camptothecin-11]. Fujiwara, T; Honjo, Y; Matsumoto, Y; Nagao, S; Sasaoka, N; Tsuchida, T, 1994)	1.93
"Camptothecin-11 (CPT-11) is a new derivative of camptothecin, a plant alkaloid antitumor agent. "	( Quantitative analysis of DNA topoisomerase I activity in human and rat glioma: characterization and mechanism of resistance to antitopoisomerase chemical, camptothecin-11. Fujiwara, T; Honjo, Y; Matsumoto, Y; Nagao, S; Sasaoka, N; Tsuchida, T, 1993)	1.93
"Camptothecin is a widely used anti-tumor drug that specifically inhibits DNA topoisomerase I. "	( The anti-cancer drug camptothecin inhibits elongation but stimulates initiation of RNA polymerase II transcription. Hanawalt, PC; Ljungman, M, 1996)	2.06
"The camptothecins are a new class of chemotherapeutic agents which have a novel mechanism of action targeting the nuclear enzyme topoisomerase I. "	( Current perspectives on camptothecins in cancer treatment. Dancey, J; Eisenhauer, EA, 1996)	1.16
"Camptothecin is an S-phase-specific anticancer agent that inhibits the activity of the enzyme DNA topoisomerase-I (topo-I). "	( Induction of neuronal apoptosis by camptothecin, an inhibitor of DNA topoisomerase-I: evidence for cell cycle-independent toxicity. Geller, HM; Morris, EJ, 1996)	2.01
"Camptothecin (CPT) is an anticancer agent with the peculiar mechanism of poisoning eukaryotic DNA topoisomerase I."	( Interactions between taxol and camptothecin. Cimoli, G; Debernardis, D; Parodi, S; Russo, P, 1996)	1.3
"Like camptothecin, CPT-11 is a selective inhibitor of the DNA enzyme topoisomerase I."	( CPT-11. The European experience. Armand, JP; Couteau, C; Rixe, O; Terret, C, 1996)	0.75
"Like camptothecin, CPT-11 is a selective DNA topoisomerase I inhibitor."	( CPT-11: the European clinical development. Armand, JP; Couteau, C; Terret, C, 1996)	0.75
"Camptothecin (CPT) is a specific topoisomerase I (top1) poison which traps top1 cleavable complexes; e.g. "	( In vivo sequencing of camptothecin-induced topoisomerase I cleavage sites in human colon carcinoma cells. Fujimori, A; Pommier, Y; Pondarré, C; Strumberg, D; Torres-León, R, 1997)	2.05
"Camptothecins are a new class of anticancer drugs that target DNA topoisomerase I; current efforts are directed toward elucidating optimal combinations of these drugs with other antineoplastic agents. "	( Mechanisms of resistance in a human cell line exposed to sequential topoisomerase poisoning. Gupta, E; Ibrahim, N; Li, XG; Mendoza, J; Pantazis, P; Patel, M; Rubin, EH; Saleem, A, 1997)	1.74
"The camptothecins are a class of potent cytotoxic anticancer agents that interact with the nuclear enzyme topoisomerase I to produce lethal DNA strand cleavages. "	( Phase I trial of the colloidal dispersion formulation of 9-amino-20(S)-camptothecin administered as a 72-hour continuous intravenous infusion. Bryant, M; Eder, JP; Kufe, DW; Lynch, T; Shulman, LN; Supko, JG; Vosburgh, E; Xu, G, 1998)	1.09
"Camptothecin (CPT) is a pentacyclic alkaloid isolated from wood and bark of Camptotheca acuminata. "	( Camptothecin and taxol: discovery to clinic. Wall, ME, 1998)	3.19
"Camptothecins (CPTs) are a unique class of chemotherapeutic agent which inhibit DNA synthesis by inhibiting topoisomerase I activity. "	( Clinical pharmacology of camptothecins. Iyer, L; Ratain, MJ, 1998)	2.05
"The camptothecins are a new class of antitumor agents that target topoisomerase I. "	( An overview of topoisomerase I-targeting agents. Arbuck, SG; Takimoto, CH, 1998)	0.86
"Camptothecin is an antitumor agent that kills cells by converting DNA topoisomerase I into a DNA-damaging poison. "	( The topoisomerase-related function gene TRF4 affects cellular sensitivity to the antitumor agent camptothecin. Castaño, IB; Christman, MF; Fitzhugh, DJ; Ju, JY; Levin, NA; Walowsky, C, 1999)	1.96
"Camptothecin is a DNA topoisomerase I poison."	( The cardioprotective and DNA topoisomerase II inhibitory agent dexrazoxane (ICRF-187) antagonizes camptothecin-mediated growth inhibition of Chinese hamster ovary cells by inhibition of DNA synthesis. Allan, WP; Chee, GL; Hasinoff, BB; Thampatty, P; Yalowich, JC, 1999)	1.24
"Camptothecin is an anticancer drug produced by the monoterpene indole alkaloid pathway in Camptotheca acuminata. "	( Tissue-specific expression of the beta-subunit of tryptophan synthase in Camptotheca acuminata, an indole alkaloid-producing plant. Lu, H; McKnight, TD, 1999)	1.75
"Homocamptothecin (hCPT) is a semisynthetic analogue of camptothecin (CPT) with a seven-membered beta-hydroxylactone resulting from the insertion of a methylene spacer between the alcohol moiety and the carboxyl function of the naturally occurring six-membered alpha-hydroxylactone of CPT. "	( Homocamptothecin, an E-ring modified camptothecin with enhanced lactone stability, retains topoisomerase I-targeted activity and antitumor properties. Bailly, C; Bigg, DC; Camara, J; Dassonneville, L; Demarquay, D; Kasprzyk, PG; Kiss, R; Lavergne, O; Lesueur-Ginot, L, 1999)	1.42
"Camptothecin (CPT) is a potent topoisomerase I inhibitor that has recently been undergoing phase I clinical trials. "	( Metabolism of camptothecin, a potent topoisomerase I inhibitor, in the isolated perfused rat liver. Hamilton, G; Jäger, W; Platzer, P; Rosenberg, E; Thalhammer, T; Ulsperger, E; Wissiack, R, 2000)	2.11
"Camptothecin (CPT) is a potent, antitumour drug acting mainly through inhibition of topoisomerase I during the S-phase of the cell cycle. "	( Polymer-bound camptothecin: initial biodistribution and antitumour activity studies. Angelucci, F; Caiolfa, VR; Castelli, MG; d'Argy, R; Farao, M; Fiorino, A; Frigerio, E; Ghiglieri, A; Gigli, M; Pellizzoni, C; Pesenti, E; Suarato, A; Zamai, M, 2000)	2.11
"PEG-camptothecin is a novel water soluble transport form (macromolecular prodrug) of the naturally derived antitumor drug, 20-(S)-camptothecin (CPT)."	( Camptothecin delivery systems: the utility of amino acid spacers for the conjugation of camptothecin with polyethylene glycol to create prodrugs. Conover, CD; Greenwald, RB; Pendri, A; Shum, KL, 1999)	2.23
"Camptothecin appears to be a poor substrate of P-glycoprotein and its intracellular accumulation is not appreciably reduced in cells expressing the multidrug-resistant phenotype."	( [Pharmacology of camptothecin and its derivatives]. Rivory, LP; Robert, J, 1995)	1.35
"Camptothecin (CPT) is a specific inhibitor of the nuclear enzyme topoisomerase I, which is involved in cellular DNA replication and transcription. "	( Camptothecin analogues with enhanced antitumor activity at acidic pH. Adams, DJ; Colvin, OM; Dewhirst, MW; Flowers, JL; Gamcsik, MP; Manikumar, G; Wall, ME; Wani, MC, 2000)	3.19
"The camptothecins are a group of anticancer agents with a unique mechanism of action: poisoning of eukaryotic DNA topoisomerase I. "	( Pharmacological determinants of 9-aminocamptothecin cytotoxicity. Firby, PS; Horn, L; Li, ML; Moore, MJ, 2001)	1.14
"The camptothecins are a new class of chemotherapeutic radiation sensitizers. "	( Camptothecin schedule and timing of administration with irradiation. Kirichenko, AV; Rich, TA, 2001)	2.31
"The camptothecins are a maturing class of anticancer agents. "	( Current perspectives on the clinical experience, pharmacology, and continued development of the camptothecins. Garcia-Carbonero, R; Supko, JG, 2002)	1.09
"Camptothecin is a potent antineoplastic agent that has shown efficacy against multiple tumor lines in vitro; unfortunately, systemic toxicity has limited its in vivo efficacy. "	( Polymer delivery of camptothecin against 9L gliosarcoma: release, distribution, and efficacy. Brem, H; Burger, PC; Moriarity, JL; Storm, PB; Tyler, B; Weingart, J, 2002)	2.08
"Camptothecin was shown to be a reversible inhibitor of virus induced interferon formation."	( The effects of some different metabolic inhibitors on interferon superinduction. Atherton, KT; Burke, DC, 1978)	0.98
"Camptothecin-11 (CPT-11) is a new semisynthetic derivative of CPT, and has been shown to inhibit DNA topoisomerase I and to have a strong antitumor activity with low toxicity in murine tumors. "	( A phase II study of CPT-11, a new derivative of camptothecin, for previously untreated non-small-cell lung cancer. Ariyoshi, Y; Fukuoka, M; Hasegawa, K; Kuriyama, T; Masuda, N; Motomiya, M; Negoro, S; Niitani, H; Nishiwaki, Y; Suzuki, A, 1992)	1.98
"Camptothecin is a specific topoisomerase I poison and is highly cytotoxic to eukaryotic cells. "	( Camptothecin cytotoxicity in mammalian cells is associated with the induction of persistent double strand breaks in replicating DNA. Johnson, RT; Ryan, AJ; Squires, S; Strutt, HL, 1991)	3.17
"Camptothecin-11 (CPT-11) is a new derivative of camptothecin, a plant alkaloid antitumor agent, and a good candidate for clinical trials because of higher antitumor activity, less toxicity, and high aqueous solubility. "	( Establishment of a camptothecin analogue (CPT-11)-resistant cell line of human non-small cell lung cancer: characterization and mechanism of resistance. Bungo, M; Fujiwara, Y; Kanzawa, F; Kasahara, K; Liu, LF; Minato, K; Nakagawa, K; Saijo, N; Sugimoto, Y, 1990)	2.05
"Camptothecin is a cytotoxic drug which inhibits cellular nucleic acid synthesis. "	( Camptothecin inhibits hsp 70 heat-shock transcription and induces DNA strand breaks in hsp 70 genes in Drosophila. Couto, E; Kroll, DJ; Rowe, TC, 1987)	3.16
"Camptothecin is an antitumor drug, which is a specific inhibitor of eukaryotic topoisomerase I. "	( Topoisomerase I interaction with SV40 DNA in the presence and absence of camptothecin. Jaxel, C; Kohn, KW; Pommier, Y, 1988)	1.95

Effects

Camptothecin (CPT) has a potent and broad-spectrum anti-tumor activity. Its clinical use is limited due to its poor water solubility, stability at physiological conditions and toxicity.

Camptothecin (CPT) has been shown to block disassembly of the topoisomerase I (Topo I)/DNA cleavable complex. It has demonstrated antitumor activity in lung, ovarian, breast, pancreas, and stomach cancers. Camptothein derivatives have been widely used for chemotherapy in patients with various cancers.

Excerpt	Reference	Relevance
"Camptothecin (CPT) has a potent and broad-spectrum anti-tumor activity but its clinical use is limited due to its poor water solubility, stability at physiological conditions and toxicity. "	( Self-microemulsifying drug delivery system for camptothecin using new bicephalous heterolipid with tertiary-amine as branching element. Akamanchi, KG; Dhumal, DM, 2018)	2.18
"Camptothecine has a strong viricidal effect on HSV-2."	( [Experimental study on the viricidal effect of rough extracts of camptothecine fruit on herpes simplex virus-2 in vitro]. Li, WW; Shi, K; Yan, ZW, 2002)	2
"Camptothecin (CPT) has been shown to block disassembly of the topoisomerase I (Topo I)/DNA cleavable complex. "	( Structure-Based Drug Design and Identification of H Chen, J; Hou, T; Huang, Y; Li, M; Li, X; Liu, F; Ni, J; Pan, P; Sun, H; Tian, S; Wang, X; Yu, H; Zhao, JJ; Zhu, F, 2018)	1.92
"Camptothecin has been shown to have antiviral activity against various viruses; however, whether it can inhibit FAdV-4 infection remains unclear."	( Antiviral and Virucidal Activities of Camptothecin on Fowl Adenovirus Serotype 4 by Blocking Virus Replication. Dai, Y; Hou, H; Hu, X; Pan, X; Qi, K; Shen, X; Wang, G; Wang, J; Yin, D; Yin, L; Zhang, D; Zhao, R, 2022)	1.71
"Camptothecin (CPT) has attracted much attention due to its potent antitumor activities. "	( Reactive oxygen species activated by mitochondria-specific camptothecin prodrug for enhanced chemotherapy. Chen, M; Chen, X; Guo, Z; Liang, R; Tian, H; Wang, Z, 2022)	2.41
"Camptothecin (CPT) has demonstrated antitumor activity in lung, ovarian, breast, pancreas, and stomach cancers. "	( The Advancement of Biodegradable Polyesters as Delivery Systems for Camptothecin and Its Analogues-A Status Report. Oledzka, E; Piotrowska, U; Sobczak, M; Strzelecka, K, 2023)	2.59
"Camptothecins (CPTs) have been reported to suppress the inflammatory response induced by sepsis."	( Liver injury in septic mice were suppressed by a camptothecin-bile acid conjugate via inhibiting NF-κB signaling pathway. Li, QY; Qi, L; Xiao, LX; Yu, ED; Yue, HL; Zhang, XL; Zhou, YQ, 2020)	1.53
"Camptothecin has been used in tumor therapy for a long time but its antitumor effect is rather limited due to the side effect and the drug resistance. "	( FEN1 inhibitor synergizes with low-dose camptothecin to induce increased cell killing via the mitochondria mediated apoptotic pathway. Gu, L; Guo, Z; He, L; Hu, Z; Jia, S; Jiang, L; Mu, D; Pan, FY; Sun, Y; Wu, C; Wu, T; Yang, Y; Zhang, J; Zhang, M; Zhang, Y; Zhu, H, 2022)	2.43
"Camptothecin (CPT) has a potent and broad-spectrum anti-tumor activity but its clinical use is limited due to its poor water solubility, stability at physiological conditions and toxicity. "	( Self-microemulsifying drug delivery system for camptothecin using new bicephalous heterolipid with tertiary-amine as branching element. Akamanchi, KG; Dhumal, DM, 2018)	2.18
"Camptothecin derivatives have been demonstrated to exert radiosensitizing effects on several types of cancer cells."	( Radiosensitization by irinotecan is attributed to G2/M phase arrest, followed by enhanced apoptosis, probably through the ATM/Chk/Cdc25C/Cdc2 pathway in p53-mutant colorectal cancer cells. Deng, W; Hu, R; Liang, L; Shen, L; Wang, Y; Yang, L; Yang, W; Yao, Y; Zhang, H; Zhang, J; Zhang, Z; Zhou, M, 2018)	1.2
"Camptothecin (CPT) has powerful biological activities and its analogs, irinothecan and topothecan, are effective anti-cancer drugs for clinical therapy. "	( A bZIP transcription factor, CaLMF, mediated light-regulated camptothecin biosynthesis in Camptotheca acuminata. Chang, C; Liu, Z; Tang, Z; Wang, Y; Yu, F, 2019)	2.2
"Camptothecin (CPT) has anticancer, antiviral, and antifungal properties. "	( Inhibitory Effect of Camptothecin against Rice Bacterial Brown Stripe Pathogen Acidovorax avenae subsp. avenae RS-2. Anjum, SI; Cai, L; Dong, Q; Hou, M; Li, B; Luo, J; Qiu, W; Sun, G; Xie, G, 2016)	2.2
"Camptothecin (CPT) has potent broad-spectrum antitumor activity by inhibiting type I DNA topoisomerase (DNA topo I). "	( Preclinical results of camptothecin-polymer conjugate (IT-101) in multiple human lymphoma xenograft models. Colcher, D; Davis, ME; Duringer, J; Forman, SJ; Kretzner, L; Numbenjapon, T; Raubitschek, A; Schluep, T; Wang, J; Yen, Y, 2009)	2.11
"Camptothecin derivatives have been widely used for chemotherapy in patients with various cancers, but intrinsic and acquired drug resistance is major drawback to be overcome. "	( Simultaneous treatment with camptothecin and valproic acid suppresses induction of Bcl-X(L) and promotes apoptosis of MCF-7 breast cancer cells. Aiba, K; Arakawa, Y; Saito, S; Yamada, H, 2009)	2.09
"Camptothecins have been characterized as inhibitors of DNA topoisomerase I (TOP1), although a correlation between TOP1 expression and activity is not well established in clinical biopsies."	( Inhibition of epidermal growth factor receptor-overexpressing cancer cells by camptothecin, 20-(N,N-diethyl) glycinate. Efferth, T; Konkimalla, VB, 2010)	1.31
"Camptothecin (CPT) has recently attracted increasing attention as a promising anticancer agent for a variety of tumors. "	( Anti-tumor activity of N-trimethyl chitosan-encapsulated camptothecin in a mouse melanoma model. Chen, XC; He, X; Li, XY; Li, ZY; Liu, XP; Qian, ZY; Wang, YM; Wei, YQ; Yi, T; Zhao, X; Zhong, Q; Zhou, LN; Zhou, ST, 2010)	2.05
"Camptothecin has shown significant antitumor activity to lung, ovarian, breast, pancreas, and stomach cancers. "	( Camptothecin delivery methods. Amsden, B; Hatefi, A, 2002)	3.2
"Camptothecine has a strong viricidal effect on HSV-2."	( [Experimental study on the viricidal effect of rough extracts of camptothecine fruit on herpes simplex virus-2 in vitro]. Li, WW; Shi, K; Yan, ZW, 2002)	2
"Camptothecin (CPT) has anticancer activity. "	( Artificial lipids stabilized camptothecin incorporated in liposomes. Hayama, A; Katayama, S; Kawano, K; Maitani, Y; Toma, K, 2008)	2.08
"Camptothecin (CPT) has been shown to induce protein-linked DNA breaks (PLDB), which are stabilized intermediates of topoisomerase I (TOP1) activity. "	( Camptothecin induction of a time- and concentration-dependent decrease of topoisomerase I and its implication in camptothecin activity. Beidler, DR; Cheng, YC, 1995)	3.18
"Camptothecin (CPT) has been recognized as a topoisomerase I (Topo I) inhibitor. "	( DNA damage and cell killing by camptothecin and its derivative in human leukemia HL-60 cells. Nakamura, T; Ueda, T; Wano, Y; Yoshida, A, 1993)	2.01
"Like camptothecin, it has been found to inhibit the topoisomerase I catalyzed relaxation of supercoiled DNA."	( Differences in the topoisomerase I cleavage complexes formed by camptothecin and wakayin, a DNA-intercalating marine natural product. Barrows, LR; Capson, TL; Holden, JA; Ireland, CM; Kokoshka, JM, 1996)	0.99
"Camptothecin has been converted for the first time to (S)-mappicine via mappicine ketone, which is the sole product of the microwave irradiation of camptothecin. "	( The first conversion of camptothecin to (S)-mappicine by an efficient chemoenzymatic method. Das, B; Kashinatham, A; Madhusudhan, P, 1998)	2.05

Actions

Camptothecins (CPT) activate S or G(2)-M arrest and the homologous recombination (HR) repair pathway in tumor cells. Camptothecin promotes the formation of a covalent complex between 32P-labeled substrate DNA and the small subunit.

Excerpt	Reference	Relevance
"Camptothecin plays an important role in clinical cancer treatment, and its derivatives are a favorite of pharmaceutical chemists. "	( A series of camptothecin prodrugs exhibit HDAC inhibition activity. Chen, Y; Li, J; Lu, W; Shen, Q; Su, M; Yu, X; Zhang, Q; Zhou, Y; Zhu, Q, 2018)	2.3
"Camptothecins (CPT) activate S or G(2)-M arrest and the homologous recombination (HR) repair pathway in tumor cells. "	( Chk1 and Chk2 are differentially involved in homologous recombination repair and cell cycle arrest in response to DNA double-strand breaks induced by camptothecins. Cai, YJ; Ding, J; Huang, M; Lu, W; Miao, ZH; Zhu, H, 2008)	1.99
"Camptothecin promotes the formation of a covalent complex between 32P-labeled substrate DNA and the small subunit."	( An unusual type IB topoisomerase from African trypanosomes. Bodley, AL; Burri, C; Chakraborty, AK; Shapiro, TA; Xie, S, 2003)	1.04
"Hydrocamptothecin promotes mRNA expression of Wnt signaling pathway inhibitor DKK-1 in Hep3B, HepG2, LoVo and U251 cells."	( [Hydrocamptothecin promotes the mRNA expression of Wnt signaling inhibitor DKK-1]. Ban, W; LA, L; Rao, JJ; Wu, SG, 2008)	1.34

Treatment

Camptothecin treatment inhibited DraTopoIB activity on intramolecular G4 DNA structures. Treatment with camptothein, a topoisomerase I inhibitor, caused normal cells to down-regulate H2AX and become quiescent.

Excerpt	Reference	Relevance
"In camptothecin-treated MCF7 and MCF7-C3 cells, choline kinase activity was unaffected; however, choline transport into cells was reduced by 30 and 60%, respectively."	( A mechanism for suppression of the CDP-choline pathway during apoptosis. Aitchison, AJ; Gehrig, K; Morton, CC; Ridgway, ND, 2013)	0.9
"Camptothecin treatment inhibited DraTopoIB activity on intramolecular G4 DNA structures."	( Topoisomerase IB of Deinococcus radiodurans resolves guanine quadruplex DNA structures in vitro. Kota, S; Misra, HS, 2015)	1.14
"Camptothecin treatment reduced the DNA relaxation activity of DNA topoisomerase I in human fibroblasts. "	( Increased susceptibility of spinal muscular atrophy fibroblasts to camptothecin is p53-independent. Funanage, VL; Gómez-Curet, I; Scavina, M; Wang, W; Wu, CY, 2009)	2.03
"Camptothecin (CPT) treatments and transient overexpression of p53 were used to investigate p53 regulation of mACON and may effects were assessed using immunoblotting and transient gene expression assays."	( p53 downregulates the gene expression of mitochondrial aconitase in human prostate carcinoma cells. Chang, PL; Feng, TH; Juang, HH; Lin, YF; Tsui, KH, 2011)	1.81
"Camptothecin treatment resulted in activation of caspase-3 with generation of the caspase-3 cleavage product, poly ADP-ribose polymerase (PARP)."	( Increased susceptibility of spinal muscular atrophy fibroblasts to camptothecin-induced cell death. Dimatteo, D; Funanage, VL; Scavina, M; Wang, W, 2005)	1.29
"Camptothecin treatment enhanced c-jun-NH2-kinase activation in response to CH-11, but inhibition of c-jun-NH2-kinase did not prevent cell death induced by the combination treatment."	( Sensitization of glioma cells to Fas-dependent apoptosis by chemotherapy-induced oxidative stress. Laterra, J; Rosen, EM; Xia, S, 2005)	1.05
"In camptothecin-treated cells, PAI-2 cleavage was an early event, detectable after 2 h of treatment, and preceding internucleosomal DNA fragmentation."	( Caspase I-related protease inhibition retards the execution of okadaic acid- and camptothecin-induced apoptosis and PAI-2 cleavage, but not commitment to cell death in HL-60 cells. Fladmark, KE; Gjertsen, BT; Jensen, PH; Vintermyr, OK, 1999)	1.04
"Camptothecin-treated cardiomyocytes were shrunken with membrane blebs and nuclear fragmentation."	( Thapsigargin enhances camptothecin-induced apoptosis in cardiomyocytes. Kong, JY; Rabkin, SW, 1999)	1.34
"Camptothecin treatments increased hprt mutations up to 50-fold over the spontaneous levels at highly cytotoxic doses."	( Molecular characterisation of camptothecin-induced mutations at the hprt locus in Chinese hamster cells. Balestrieri, E; Degrassi, F; Zanier, R, 2001)	1.32
"Camptothecin treated HUVEC released different populations of annexin V-binding membrane microparticles at early stage after proapoptotic stimulation before detection of phosphatidylserine exposure on the cells or DNA fragmentation. "	( Release of annexin V-binding membrane microparticles from cultured human umbilical vein endothelial cells after treatment with camptothecin. Holada, K; Simák, J; Vostal, JG, 2002)	1.96
"Camptothecin treatment of Ramos B cells leads to the degradation of Rb protein and phosphorylation of its family members, p107 and p130."	( Differential regulation of Rb family proteins and prohibitin during camptothecin-induced apoptosis. Chellappan, S; Fusaro, G; Wang, S, 2002)	1.27
"Camptothecin treatment decreases tyrosine aminotransferase mRNA levels and inhibits transcription."	( Camptothecin-induced in vivo topoisomerase I cleavages in the transcriptionally active tyrosine aminotransferase gene. Schütz, G; Stewart, AF, 1987)	2.44
"Treatment with camptothecin, triptolide and/or apoptosis inducer kit results in differential effects of fission on apoptosis in these cells."	( Camptothecin, triptolide, and apoptosis inducer kit have differential effects on mitochondria in colorectal carcinoma cells. Chovancova, B; Kajsik, M; Krizanova, O; Liskova, V; Roller, L, 2022)	2.5
"Rats treated with camptothecin subsequent to a brain tumor graft survived longer when the drug was delivered by Bom/PEG-PCL-Tat mixed micelles than by PEG-PCL-Tat micelles."	( Nose-to-brain drug delivery system with ligand/cell-penetrating peptide-modified polymeric nano-micelles for intracerebral gliomas. Kanazawa, T; Okada, H; Taki, H, 2020)	0.88
"Treatment with camptothecin which transiently stabilized nucleolar R-loops recruited RNase H1 to the nucleoli."	( Dynamic nucleoplasmic and nucleolar localization of mammalian RNase H1 in response to RNAP I transcriptional R-loops. Bailey, JK; Crooke, ST; De Hoyos, CL; Liang, XH; Shen, W; Sun, H, 2017)	0.79
"Treatment with camptothecin, a topoisomerase I inhibitor, caused normal cells to down-regulate H2AX and become quiescent, a process mediated by both Arf and p53."	( The Arf/p53 protein module, which induces apoptosis, down-regulates histone H2AX to allow normal cells to survive in the presence of anti-cancer drugs. Atsumi, Y; Fujimori, H; Inase, A; Kanno, M; Masutani, M; Nakagama, H; Osawa, T; Sakasai, R; Saya, H; Sugihara, E; Tashiro, F; Teraoka, H; Yoshioka, K, 2013)	0.73
"When treated with camptothecin (CPT), an inhibitor of DNA topoisomerase I, WRN(-/-) cells showed higher sensitivity than wild-type cells, whereas KU70(-/-) and DNA-PKcs(-/-/-) cells showed hyper-resistance."	( WRN counteracts the NHEJ pathway upon camptothecin exposure. Abe, T; Dong, YP; Enomoto, T; Inoue, E; Kato, G; Kawabe, Y; Otsuki, M; Seki, M; Tada, S; Yoshimura, A, 2007)	0.93
"Treatment with camptothecin and amsacrine increased the apparent A/B ratio by factors of 2-3 and 1.5-2 respectively, indicating that the active B allele is preferentially damaged by these agents."	( Selective damage to the active X chromosome by camptothecin and amsacrine as determined by an allele-specific alkaline unwinding assay. Austin, MJ; Bunch, RT; Povirk, LF, 1995)	0.89
"Treatment with camptothecin and a 131I-labeled control antibody was no more effective than treatment with drug alone."	( Potentiation of radioimmunotherapy by inhibition of topoisomerase I. Chan, J; Roffler, SR; Yeh, MY, 1994)	0.63
"Treatment with camptothecin caused a threefold increase in the activity of c-Jun N-terminal kinase (JNK) and an eightfold increase in the level of phosphorylated c-Jun."	( pRb suppresses camptothecin-induced apoptosis in human osteosarcoma Saos-2 cells by inhibiting c-Jun N-terminal kinase. Calvaruso, G; Carabillò, M; D'Anneo, A; Emanuele, S; Giuliano, M; Lauricella, M; Tesoriere, G; Vento, R, 2001)	1
"Cotreatment with camptothecin reduced m-AMSA-mediated cytotoxicity in G1-phase V79 cells, suggesting a possible antagonism between topoisomerase I and II poisons."	( Involvement of nucleic acid synthesis in cell killing mechanisms of topoisomerase poisons. Beardmore, C; D'Arpa, P; Liu, LF, 1990)	0.61

Toxicity

Camptothecin (CPT) is a plant alkaloid originally isolated from the native Chinese tree, Camptotheca acuminate. It exerts the toxic effect by targeting eukaryotic DNA topoisomerase 1 (DNA Topo1) Irreversible DNA double-strand breaks are produced during DNA synthesis in the presence of CPT.

Excerpt	Reference	Relevance
" At levels of the drug which are toxic to the cell, these breaks are long-lived, and still measurable 24 hr after treatment."	( Camptothecin cytotoxicity in mammalian cells is associated with the induction of persistent double strand breaks in replicating DNA. Johnson, RT; Ryan, AJ; Squires, S; Strutt, HL, 1991)	1.72
" The LD50 for camptothecin was in the 12."	( Camptothecin cytotoxic effects in vitro: dependency on exposure duration and dose. Ainsworth, S; Helson, C; Helson, L, 1995)	2.09
" The principal adverse events of CPT-11 are neutropenia and delayed diarrhea, which in the European studies developed as grade 3 or 4 toxicity in 21% and 12% of the cycles (47% and 38% of patients), respectively."	( CPT-11 in the treatment of colorectal cancer: clinical efficacy and safety profile. Bugat, R; Rougier, P, 1996)	0.29
" Recently we have shown that false-positive results can still be obtained due to cytotoxicity when loss of membrane integrity is a late event in toxic cell death relative to the induction of endonucleolytic DNA degradation."	( Revalidation of the in vitro alkaline elution/rat hepatocyte assay for DNA damage: improved criteria for assessment of cytotoxicity and genotoxicity and results for 81 compounds. Barnum, JE; DeLuca, JG; Elia, MC; Harmon, LS; Kraynak, AR; McKelvey, TW; Nichols, WW; Storer, RD, 1996)	0.29
" Irreversible DNA double-strand breaks are produced during DNA synthesis in the presence of camptothecin, suggesting that this agent should not be toxic to nondividing cells, such as neurons."	( Induction of neuronal apoptosis by camptothecin, an inhibitor of DNA topoisomerase-I: evidence for cell cycle-independent toxicity. Geller, HM; Morris, EJ, 1996)	0.79
" In a pivotal French study in which CPT-11 350 mg/m2 was administered once every 3 weeks, neutropenia and delayed diarrhoea were the major adverse events: transient neutropenia occurred in 80% of patients, and severe neutropenia and febrile neutropenia in 47 and 15%, respectively."	( Characterisation and clinical management of CPT-11 (irinotecan)-induced adverse events: the European perspective. Bleiberg, H; Cvitkovic, E, 1996)	0.29
" These data show that oral administration of JBT 3002 can prevent irinotecan-induced gastrointestinal toxic effects and maintain the integrity of the lamina propria, thus allowing for intensification of irinotecan therapy against liver metastases from colon cancer."	( Prevention of intestinal toxic effects and intensification of irinotecan's therapeutic efficacy against murine colon cancer liver metastases by oral administration of the lipopeptide JBT 3002. Fidler, IJ; Killion, JJ; Kumar, R; Kuniyasu, H; Shinohara, H, 1998)	0.3
" Participation by both the oncology care team and patients is crucial for effective side effect management."	( Managing the side effects of chemotherapy for colorectal cancer. Berg, D, 1998)	0.3
" Delayed diarrhea and neutropenia are the most common toxic side effects, both of which can usually be predicted, by knowing the criteria for patients who are at increased risk for those side effects."	( Colorectal cancer: dilemmas regarding patient selection and toxicity prediction. Jelic, S; Nikolic-Tomasevic, Z; Popov, I; Radosavljevic, D, 2000)	0.31
" These results demonstrate that CPT derivatives are directly toxic to liver cells in a distinct time- and dose-related response."	( Hepatotoxicity of camptothecin derivatives in a primary culture system of rat hepatocytes. Costa, C; Costa, G; Fulco, RA; Germanò, MP; Giudice, A; Maisano, R; Salimbeni, V; Torre, EA; Viscomi, MG, 2000)	0.64
" In an interim analysis of nine patients, thalidomide had almost eliminated the dose-limiting gastrointestinal toxic effects of irinotecan, especially diarrhoea and nausea (each p<0."	( Effect of thalidomide on gastrointestinal toxic effects of irinotecan. Broadwater, R; Govindarajan, R; Hauer-Jensen, M; Heaton, KM; Lang, NP; Zeitlin, A, 2000)	0.31
" As the clinical indications for the use of this agent expand, we describe irinotecan-associated interstitial pneumonitis as a serious potential adverse effect."	( Irinotecan-associated pulmonary toxicity. Bjarnason, GA; Madarnas, Y; Shorter, AM; Webster, P, 2000)	0.31
" 9-aminocamptothecin glucuronide was 25-60 times less toxic than 9-aminocamptothecin to five human cancer cell lines."	( Anti-tumour activity and toxicity of the new prodrug 9-aminocamptothecin glucuronide (9ACG) in mice. Chen, BM; Chern, JW; Leu, YL; Prijovich, ZM; Roffler, SR, 2002)	0.99
" DLPC-only liposome also had no toxic effects."	( 9-nitrocamptothecin liposome aerosol: lack of subacute toxicity in dogs. Brayton, C; Gilbert, BE; Knight, V; Seryshev, A, 2002)	0.77
" The most common treatment-related adverse events reported during therapy with IMC-C225 were an acne-like rash and hypersensitivity reactions."	( Safety experience with IMC-C225, an anti-epidermal growth factor receptor antibody. Needle, MN, 2002)	0.31
" Thus we sought to determine in a rat model whether extending the period of infusion of CPT-11 would ameliorate the adverse reactions."	( Alleviation of side effects induced by irinotecan hydrochloride (CPT-11) in rats by intravenous infusion. Hashimoto, S; Kado, S; Kaneda, N; Kurita, A; Onoue, M; Yokokura, T, 2003)	0.32
" The pharmacokinetic parameters suggested that the Cmax of CPT-11 is closely related to the incidence and severity of adverse reactions such as myelosuppression and acute and delayed-onset diarrhea."	( Alleviation of side effects induced by irinotecan hydrochloride (CPT-11) in rats by intravenous infusion. Hashimoto, S; Kado, S; Kaneda, N; Kurita, A; Onoue, M; Yokokura, T, 2003)	0.32
" Grade 2 toxic effects included nausea/vomiting (9 patients), cough and bronchial irritation (6 patients), fatigue (5 patients), anemia (4 patients), neutropenia (2 patients), anorexia (1 patient), and skin rash around the face mask (1 patient)."	( Clinical evaluation of the delivery and safety of aerosolized liposomal 9-nitro-20(s)-camptothecin in patients with advanced pulmonary malignancies. Gilbert, BE; Huaringa, A; Knight, V; Loyer, E; Newman, RA; Verschraegen, CF; Walsh, G, 2004)	0.55
" Oral administration of RDP58 significantly decreased the incidence of diarrhea and improved the survival rates of mice treated with toxic doses of CPT-11 or 5-fluorouracil."	( Oral RDP58 allows CPT-11 dose intensification for enhanced tumor response by decreasing gastrointestinal toxicity. Belmar, N; Buelow, R; Fong, T; Huang, L; Zhao, J, 2004)	0.32
" Adverse events were monitored following NCI-CTC."	( Safety, tolerability, pharmacokinetics, and pharmacodynamics of an orally active novel camptothecin analog, DRF-1042, in refractory cancer patients in a phase I dose escalation study. Chatterjee, A; Digumarti, R; Jiwatani, S; Katneni, K; Mamidi, RN; Srinivas, ML; Srinivas, NR; Subramaniam, S; Surath, A; Uppalapati, S; Upreti, VV, 2004)	0.55
"We wanted to assess polymorphisms in the uridine diphosphoglucuronosyl transferase 1A1 (UGT 1A1) gene: the TATA box polymorphism and UGT 1A1 G71R and Y486D mutations in the coding sequence, the main mutations characterizing Gilbert's syndrome, as predictors of severe toxic event occurrence after irinotecan (CPT-11) administration."	( Relevance of different UGT1A1 polymorphisms in irinotecan-induced toxicity: a molecular and clinical study of 75 patients. Boisdron-Celle, M; Dumont, A; Gamelin, E; Guérin, O; Morel, A; Rouits, E, 2004)	0.32
" There were no adverse effects in the low and middle dose groups of both genders."	( Subacute toxicity evaluation of a new camptothecin anticancer agent CKD-602 administered by intravenous injection to rats. Chung, MK; Ha, CS; Kim, CY; Kim, JC; Kim, JK; Kim, SH; Lee, HS; Park, SC; Shin, DH; Son, WC; Suh, JE, 2004)	0.59
" The most frequent toxic effects were grade 3/4 diarrhea (arm A: 34%, B: 19%), grade 3/4 neutropenia (A: 5%, B: 19%) and grade 2/3 alopecia (A: 26%, B: 65%)."	( A randomized phase II trial of capecitabine and two different schedules of irinotecan in first-line treatment of metastatic colorectal cancer: efficacy, quality-of-life and toxicity. Bernhard, J; Borner, MM; Brauchli, P; Dietrich, D; Herrmann, R; Honegger, H; Koeberle, D; Lanz, D; Popescu, R; Rauch, D; Roth, AD; Saletti, P; Wernli, M, 2005)	0.33
" No treatment-related adverse effects were observed in both sexes of the low and middle dose groups."	( 4-Week repeated intravenous dose toxicity study of a new camptothecin anticancer agent CKD-602 in dogs. Cha, SW; Cho, KH; Chung, MK; Kang, BH; Kim, HC; Kim, JC; Kim, YB; Park, SC; Park, SH; Shin, DH, 2005)	0.57
" Adverse events were monitored following NCI-CTC."	( Safety, tolerability, and pharmacokinetics of a capsule formulation of DRF-1042, a novel camptothecin analog, in refractory cancer patients in a bridging phase I study. Chatterjee, A; Digumarti, R; Jiwatani, S; Katneni, K; Mamidi, RN; Mullangi, R; Srinivas, ML; Srinivas, NR; Surath, A; Uppalapati, S; Upreti, VV, 2005)	0.55
" As a side effect of the therapy, a follicular rash often develops in the seborrheic areas; this cutaneous reaction is associated with longer survival."	( [Follicular drug reaction from cetuximab: a common side effect in the treatment of metastatic colon carcinoma]. Braun-Falco, M; Holtmann, C; Lordick, F; Ring, J, 2006)	0.33
"These findings, combined with the observation of clinical activity and grade 3/4 neutropenia in 25% of patients, suggest that combining chrysin with CPT-11 may be a safe and potentially useful means of preventing diarrhoea, although this needs to be further investigated in the setting of a randomised trial."	( A pilot study on the safety of combining chrysin, a non-absorbable inducer of UGT1A1, and irinotecan (CPT-11) to treat metastatic colorectal cancer. Beale, P; Clarke, S; Liddell, S; Noney, L; Rivory, LP; Tobin, PJ, 2006)	0.33
"Irinotecan hydrochloride shows much different responses in each patient, and it has severe adverse effects."	( [Assessment of immunotoxicity of irinotecan determined by the novel method, by which productivity of TNF-alpha from whole blood is stimulated by lipopolysaccharide]. Araki, H; Ishizaki, M; Kamiyama, Y; Kawaguchi, Y; Komiyama, Y; Nakagawa, A; Nishimura, N; Takahashi, H, 2005)	0.33
" Adverse effects associated with the Saltz regimen included diarrhea and neutropenia."	( Concomitant administration of bevacizumab, irinotecan, 5-fluorouracil, and leucovorin: nonclinical safety and pharmacokinetics. Bricarello, A; Christian, BJ; Gaudreault, J; Mounho, B; Shiu, V; Zuch, CL, )	0.13
" It is experientially clear that inter-individual differences exist in the degree of efficacy and occurrence of adverse effects."	( [SNPs associated with adverse effects]. Isomura, M; Miki, Y, 2005)	0.33
"The weekly dosing schedule of irinotecan seems to be effective and safe salvage chemotherapy regimen for platinum- and taxanes-resistant or refractory epithelial ovarian cancer."	( The safety and efficacy of the weekly dosing of irinotecan for platinum- and taxanes-resistant epithelial ovarian cancer. Andoh, M; Fujiwara, Y; Katsumata, N; Kohno, T; Matsumoto, K; Shimizu, C; Yamanaka, Y; Yonemori, K, 2006)	0.33
" During the whole study period, the common grade 3/4 adverse events were acne-like rash (38%) and diarrhea (29%)."	( Cetuximab and irinotecan/5-fluorouracil/folinic acid is a safe combination for the first-line treatment of patients with epidermal growth factor receptor expressing metastatic colorectal carcinoma. Folprecht, G; Köhne, CH; Lutz, MP; Nolting, A; Pollert, P; Schöffski, P; Seufferlein, T, 2006)	0.33
"Addition of cetuximab to weekly infusional 5-FU/FA plus irinotecan is safe and first data suggest a promising activity."	( Cetuximab and irinotecan/5-fluorouracil/folinic acid is a safe combination for the first-line treatment of patients with epidermal growth factor receptor expressing metastatic colorectal carcinoma. Folprecht, G; Köhne, CH; Lutz, MP; Nolting, A; Pollert, P; Schöffski, P; Seufferlein, T, 2006)	0.33
"In the current Phase II study, the authors evaluated the association between genomic polymorphic variants in uridine diphosphate glucuronosyl transferase (UGT1A1), methylenetetrahydrofolate reductase (MTHFR), and thymidylate synthase (TS) genes, and the incidence of the adverse effects of irinotecan and raltitrexed in previously heavily treated patients with metastatic colorectal carcinoma."	( Uridine diphosphate glucuronosyl transferase 1A1 promoter polymorphism predicts the risk of gastrointestinal toxicity and fatigue induced by irinotecan-based chemotherapy. Bisonni, R; Leon, A; Lippe, P; Lombardo, M; Marcucci, F; Massacesi, C; Mattioli, R; Pilone, A; Rocchi, MB; Terrazzino, S, 2006)	0.33
" Nineteen variables related to patient, disease, and treatment characteristics, together with genotypes, were analyzed using a binary logistic regression model with stepwise selection to evaluate their correlation with adverse reactions."	( Uridine diphosphate glucuronosyl transferase 1A1 promoter polymorphism predicts the risk of gastrointestinal toxicity and fatigue induced by irinotecan-based chemotherapy. Bisonni, R; Leon, A; Lippe, P; Lombardo, M; Marcucci, F; Massacesi, C; Mattioli, R; Pilone, A; Rocchi, MB; Terrazzino, S, 2006)	0.33
" MTHFR C677T polymorphism was not found to be associated with any adverse reaction."	( Uridine diphosphate glucuronosyl transferase 1A1 promoter polymorphism predicts the risk of gastrointestinal toxicity and fatigue induced by irinotecan-based chemotherapy. Bisonni, R; Leon, A; Lippe, P; Lombardo, M; Marcucci, F; Massacesi, C; Mattioli, R; Pilone, A; Rocchi, MB; Terrazzino, S, 2006)	0.33
"Delayed diarrhea is the most important side effect of irinotecan."	( Intestinal microflora and digestive toxicity of irinotecan in mice. Biasco, G; Brandi, G; Bridonneau, C; Dabard, J; De Vivo, A; Di Battista, M; Morselli Labate, AM; Pantaleo, MA; Pisi, AM; Raibaud, P, 2006)	0.33
" The water-soluble salt camptothecin-sodium - introduced in early trials in the 1960s - was highly toxic in animals, whereas the semisynthetic derivatives irinotecan and topotecan did not cause haemorrhagic cystitis because of their higher physicochemical stability and solubility at lower pH values."	( Camptothecin and podophyllotoxin derivatives: inhibitors of topoisomerase I and II - mechanisms of action, pharmacokinetics and toxicity profile. Hartmann, JT; Lipp, HP, 2006)	2.08
"Our data show that whereas TRAIL alone or together with selected chemotherapeutic drugs seems to be safe, the combination of TRAIL with cisplatin is toxic to PHH."	( Preclinical differentiation between apparently safe and potentially hepatotoxic applications of TRAIL either alone or in combination with chemotherapeutic drugs. Büchler, P; Ganten, TM; Haas, TL; Koschny, R; Schader, MB; Schulze-Bergkamen, H; Stremmel, W; Sykora, J; Untergasser, A; Walczak, H, 2006)	0.33
" However, some nondermatologic adverse events can also be common."	( Nondermatologic adverse events associated with anti-EGFR therapy. Sandler, AB, 2006)	0.33
"The Food and Drug Administration (FDA) has approved label changes for two anticancer drugs, 6-mercaptopurine (6-MP) and irinotecan, to include pharmacogenetic testing as a potential means to reduce the rate of severe toxic events."	( TPMT, UGT1A1 and DPYD: genotyping to ensure safer cancer therapy? Maitland, ML; Ratain, MJ; Vasisht, K, 2006)	0.33
" Our data suggest that GSTT1-null is associated with a greater probability of developing toxicity to 5-Fu/CPT-11/Lv treatments, indicating a potential application of this genetic analysis in predicting adverse effects of this regimen."	( Potential application of GSTT1-null genotype in predicting toxicity associated to 5-fluouracil irinotecan and leucovorin regimen in advanced stage colorectal cancer patients. Aranda, E; Bandres, E; De la Haba, J; Garcia, F; García-Foncillas, J; Gómez, A; Huarriz, M; Morales, R; Romero, RZ, 2006)	0.33
" This study examined the potential adverse effects of CKD-602 on pregnancy, delivery, and lactation in female Sprague-Dawley rats as well as on the pre- and postnatal development of their offspring."	( Reproductive toxicity evaluation of a new camptothecin anticancer agent, CKD-602, in pregnant/lactating female rats and their offspring. Chung, MK; Kim, CY; Kim, JC, 2007)	0.6
" End points included grade > or = 3 adverse events, response rate (in advanced disease), progression or relapse-free survival, dose-intensity, and overall survival in the studies with mature survival data."	( Pooled analysis of safety and efficacy of oxaliplatin plus fluorouracil/leucovorin administered bimonthly in elderly patients with colorectal cancer. Andre, T; Bleiberg, H; de Gramont, A; Goldberg, RM; Green, E; Rothenberg, ML; Sargent, DJ; Tabah-Fisch, I; Tournigand, C, 2006)	0.33
" Older age was not associated with increased rates of severe neurologic adverse events, diarrhea, nausea/vomiting, infection, overall incidence of grade > or = 3 toxicity (63% v 67%; P = ."	( Pooled analysis of safety and efficacy of oxaliplatin plus fluorouracil/leucovorin administered bimonthly in elderly patients with colorectal cancer. Andre, T; Bleiberg, H; de Gramont, A; Goldberg, RM; Green, E; Rothenberg, ML; Sargent, DJ; Tabah-Fisch, I; Tournigand, C, 2006)	0.33
" We present a colon cancer patient with the UGT1A1 polymorphism (UGT1A1 *28) as a known high risk for irinotecan, who was treated with a combination of doxifluridine and irinotecan for peritoneal dissemination resulting in stable disease for 2 years without adverse reactions, although the patient initially developed severe adverse effects to the combination of the protracted venous infusion of 5-FU and irinotecan."	( Irinotecan cytotoxicity does not necessarily depend on the UGT1A1 polymorphism but on fluoropyrimidine: a molecular case report. Hiro, J; Inoue, Y; Kusunoki, M; Miki, C; Nakatani, K; Nobori, T; Ojima, E; Toiyama, Y; Watanabe, H, 2006)	0.33
"9% toxic deaths."	( Clinical predictors of severe toxicity in patients treated with combination chemotherapy with irinotecan and/or oxaliplatin for metastatic colorectal cancer: a single center experience. Aparicio, J; Díaz, R; Giménez, A; Gómez-Codina, J; Molina, J; Palomar, L; Ponce, J; Segura, A, 2006)	0.33
" We conducted a study to identify a safe dose and potential drug-drug interactions of this combination."	( Pharmacokinetic and safety study of weekly irinotecan and oral capecitabine in patients with advanced solid cancers. Baker, S; Bulgaru, A; Camacho, F; Chaudhary, I; Desai, K; Einstein, M; Goel, S; Goldberg, G; Gollamudi, R; Karri, S; Kaubisch, A; Mani, S, 2007)	0.34
" The combination of irinotecan and capecitabine is safe and well tolerated at 100/2000, and warrants further evaluation in ovarian and breast cancer."	( Pharmacokinetic and safety study of weekly irinotecan and oral capecitabine in patients with advanced solid cancers. Baker, S; Bulgaru, A; Camacho, F; Chaudhary, I; Desai, K; Einstein, M; Goel, S; Goldberg, G; Gollamudi, R; Karri, S; Kaubisch, A; Mani, S, 2007)	0.34
" Toxicity assessment of new 1,2,4-triazoles revealed significant differences in their toxic potential, and the results indicate the same sensitivity profile among the assays as observed with the standard compounds."	( Assessing the data quality in predictive toxicology using a panel of cell lines and cytotoxicity assays. Pohjala, L; Samanta, SK; Tammela, P; Vuorela, P; Yli-Kauhaluoma, J, 2007)	0.34
" The relation between adverse events on IROX to selected characteristics was analyzed."	( Updated efficacy and toxicity analysis of irinotecan and oxaliplatin (IROX) : intergroup trial N9741 in first-line treatment of metastatic colorectal cancer. Alberts, SR; Ashley, AC; Campbell, ME; Findlay, BP; Fuchs, CS; Goldberg, RM; Grothey, A; Morton, RF; Pitot, HC; Ramanathan, RK; Sargent, DJ; Williamson, SK, 2007)	0.34
" Fifty-two percent of patients required dose reductions for adverse events, and 26% experienced 119 hospitalizations related to complications of treatment or their disease, with 5 treatment-related deaths."	( Updated efficacy and toxicity analysis of irinotecan and oxaliplatin (IROX) : intergroup trial N9741 in first-line treatment of metastatic colorectal cancer. Alberts, SR; Ashley, AC; Campbell, ME; Findlay, BP; Fuchs, CS; Goldberg, RM; Grothey, A; Morton, RF; Pitot, HC; Ramanathan, RK; Sargent, DJ; Williamson, SK, 2007)	0.34
" Since their adverse effects are not well elucidated, in this study the efficiency of HI-6 oxime in protection and/or reactivation of human erythrocyte AChE inhibited by the antineoplastic drug irinotecan as well as its cyto/genotoxicity in vitro were investigated."	( Evaluation of HI-6 oxime: potential use in protection of human acetylcholinesterase inhibited by antineoplastic drug irinotecan and its cyto/genotoxicity in vitro. Berend, S; Fuchs, N; Kopjar, N; Radić, B; Vrdoljak, AL; Zeljezić, D, 2007)	0.34
" Main grade 3/4 toxic effects were, respectively, neutropenia 42."	( A randomized phase II trial evaluating safety and efficacy of an experimental chemotherapy regimen (irinotecan + oxaliplatin, IRINOX) and two standard arms (LV5 FU2 + irinotecan or LV5 FU2 + oxaliplatin) in first-line metastatic colorectal cancer: a study Adenis, A; Bécouarn, Y; Boucher, E; Cany, L; Cvitkovic, F; Jacob, JH; Montoto-Grillot, C; Senesse, P; Thézenas, S; Ychou, M, 2007)	0.34
"Cetuximab-based combination chemotherapy (CBCC) proved safe and effective as second-line strategy for metastatic colorectal cancer (mCRC)."	( Safety and efficacy of cetuximab-chemotherapy combination in Saudi patients with metastatic colorectal cancer. Al-Gahmi, AM; Bahadur, YA; Fawzi, EE; Ibrahim, EM; Sallam, YA; Zeeneldin, AA, )	0.13
"Chemoradiotherapy of the last phase II study with intermittent capecitabine (1500 mg/m(2)/day, delivered on days 1-14 and 22-35) and irinotecan (4 x 60 mg/m(2)) concurrently to radiotherapy is a safe treatment with low toxicity and high efficacy."	( Intensified irinotecan-based neoadjuvant chemoradiotherapy in rectal cancer: four consecutive designed studies to minimize acute toxicity and to optimize efficacy measured by pathologic complete response. Fietkau, R; Foitzik, T; Klar, E; Klautke, G; Küchenmeister, U; Ludwig, K; Prall, F; Semrau, S, 2007)	0.34
" Administration of TroVax alongside chemotherapy was safe and well tolerated with no SAEs attributed to the vaccine and no enhancement of chemo-related toxicity."	( Vaccination of colorectal cancer patients with TroVax given alongside chemotherapy (5-fluorouracil, leukovorin and irinotecan) is safe and induces potent immune responses. Carroll, MW; Chikoti, P; Drury, N; Griffiths, R; Harrop, R; Hawkins, RE; Kingsman, SM; Naylor, S; Redchenko, I; Shingler, W; Steven, N, 2008)	0.35
"Genotyping of the UGT1A1*28, UGT1A7 N129K/R131K, and UGT1A7-57T/G variants was done in 105 irinotecan-treated patients with metastatic colorectal cancer; adverse events were documented during all 297 treatment cycles and analyzed by Cochran-Mantel-Haenszel, Mann-Whitney, and chi2 tests."	( Gilbert's Syndrome and irinotecan toxicity: combination with UDP-glucuronosyltransferase 1A7 variants increases risk. Erichsen, TJ; Heinemann, V; Lankisch, TO; Manns, MP; Schulz, C; Strassburg, CP; Zwingers, T, 2008)	0.35
"The presence of UGT1A7 but not UGT1A1 variants was associated with at least one adverse event."	( Gilbert's Syndrome and irinotecan toxicity: combination with UDP-glucuronosyltransferase 1A7 variants increases risk. Erichsen, TJ; Heinemann, V; Lankisch, TO; Manns, MP; Schulz, C; Strassburg, CP; Zwingers, T, 2008)	0.35
"An increase of sIL-2R, CD4+CD25+ T-cells and the CD4/8 ratio in patients with symptomatic adverse reactions were found."	( Changes of immunological parameters reflect quality of life-related toxicity during chemotherapy in patients with advanced colorectal cancer. Aizawa, M; Fujimoto, T; Itagaki, H; Kobayashi, R; Kuhara, K; Ogawa, K; Osawa, G; Otani, T; Yokomizo, H; Yoshimatsu, K, )	0.13
" Evaluation points included adverse events, dose intensity, response rate, progression-free survival, and overall survival."	( Safety of irinotecan and infusional fluorouracil/leucovorin (FOLFIRI) in Japan: a retrospective review of 48 patients with metastatic colorectal cancer. Asaka, M; Doi, T; Fuse, N; Hamamoto, Y; Minashi, K; Muto, M; Ohtsu, A; Tahara, M; Yano, T; Yoshida, S, 2008)	0.35
" However, translation to clinical practice of UGT1A1*28 testing as a predictive marker of adverse effects needs to be further investigated and the available data are not conclusive in defining a precise genotype-based dosage."	( UGT1A1*28 and other UGT1A polymorphisms as determinants of irinotecan toxicity. Biason, P; Masier, S; Toffoli, G, 2008)	0.35
" Many drugs have been used for the treatment of this disease, but there is little information about how predictive factors can be used to aid treatment response and anticipate toxic effects related to anticancer treatment in colorectal cancer."	( Predictive factors for chemotherapy-related toxic effects in patients with colorectal cancer. Pantano, F; Santini, D; Schiavon, G; Tonini, G; Vincenzi, B, 2008)	0.35
"The toxicity of irinotecan is predictable, manageable and nonadditive in the majority of patients; however, with its increasing use alone and in combination with other agents and modalities, the recognition and control of these adverse effects remain a clinical challenge."	( Irinotecan toxicity. Anthony, L, 2007)	0.34
"For advanced or metastatic colorectal cancer, FOLFOX4/mFOLFOX6 followed by FOLFIRI may be effective and comparatively safe treatments."	( Efficacy and toxicity of fluorouracil, leucovorin plus oxaliplatin (FOLFOX4 and modified FOLFOX6) followed by fluorouracil, leucovorin plus irinotecan(FOLFIRI)for advanced or metastatic colorectal cancer--case studies. Adachi, K; Arimoto, Y; Kanamiya, Y; Nakamura, R; Nishio, K; Oba, H; Ohtani, H; Shintani, M; Yui, S, 2008)	0.35
"76%) discontinued treatment due to a treatment-emergent adverse event, including one with end-stage renal failure and another with gastric perforation."	( Efficacy, safety and patterns of response and recurrence in patients with recurrent high-grade gliomas treated with bevacizumab plus irinotecan. Anderson, J; Doyle, T; Ellika, S; Jain, R; Mikkelsen, T; Schultz, L; Torcuator, R; Zuniga, RM, 2009)	0.35
"The use of excipients as inhibitors of BCRP is safe and relatively non-toxic, and may lead to important pharmacotherapeutic benefits by decreasing the gastrointestinal toxicity of CPT."	( Effects of breast cancer resistance protein inhibitors and pharmaceutical excipients on decreasing gastrointestinal toxicity of camptothecin analogs. Gan, L; Gan, Y; Pan, WS; Zhang, XX; Zhu, CL, 2008)	0.55
"We report a successful case of chemotherapy accompanied with grade 4 adverse events for unresectable advanced gastric cancer."	( [A case of unresectable advanced gastric cancer successfully treated with continuous S-1 + CPT-11 chemotherapy accompanied by dose reduction against grade 4 hematological adverse event]. Furukawa, H; Imamura, H; Kishimoto, T; Miyazaki, Y; Ota, K; Tatsuta, M, 2008)	0.35
" The most important adverse event was abdominal pain."	( TACE of liver metastases from colorectal cancer adopting irinotecan-eluting beads: beneficial effect of palliative intra-arterial lidocaine and post-procedure supportive therapy on the control of side effects. Aliberti, C; Ballardini, PL; Benea, G; Cantore, M; Fiorentini, G; Mambrini, A; Montagnani, F, )	0.13
" All pharmacologic agents in current use have been associated with adverse events."	( Toxic effects and their management: daily clinical challenges in the treatment of colorectal cancer. Eng, C, 2009)	0.35
" Major adverse events were neutropenia, nausea, diarrhea, hand/foot syndrome, and neurotoxicity."	( Efficacy and safety of capecitabine and oxaliplatin combination as second-line treatment in advanced colorectal cancer. Hatzopoulos, A; Heras, P; Karagiannis, S; Kritikos, K; Kritikos, N; Mitsibounas, D; Xourafas, V, )	0.13
" Serious/grade 3-5 adverse events of interest for bevacizumab included bleeding (3%), gastrointestinal perforation (2%), arterial thromboembolism (1%), hypertension (5."	( Safety and efficacy of first-line bevacizumab with FOLFOX, XELOX, FOLFIRI and fluoropyrimidines in metastatic colorectal cancer: the BEAT study. Berry, S; Bridgewater, J; Canon, JL; Cunningham, D; DiBartolomeo, M; Georgoulias, V; Kretzschmar, A; Mazier, MA; Michael, M; Peeters, M; Rivera, F; Van Cutsem, E, 2009)	0.35
"In this large pooled analysis, we found MMC, when capped at a cumulative dose of 36 mg/m(2), to be safe and tolerable in combination with capecitabine or irinotecan with no reportable cases of TTP/HUS."	( Capped-dose mitomycin C: a pooled safety analysis from three prospective clinical trials. Arce-Lara, C; Bekaii-Saab, T; Cataland, S; Kraut, E; Ntukidem, N; Otterson, GA, 2010)	0.36
" The most common adverse events were leukopenia (73."	( [Efficacy and safety of combination of irinotecan and capecitabine in patients with metastatic colorectal cancer after failure of chemotherapy with oxaliplatin]. Bai, CM; Chen, SC; Cheng, YJ; Jia, N; Shao, YJ; Zhou, JF, 2009)	0.35
" Docetaxel, cisplatin, 5-fluorouracil (DCF) is effective, but highly toxic regimen for advanced cases."	( The efficacy and safety of reduced-dose docetaxel, cisplatin, and 5-fluorouracil in the first-line treatment of advanced stage gastric adenocarcinoma. Abali, H; Budakoglu, B; Güler, T; Odabaşi, H; Oksüzoğlu, B; Ozdemir, NY; Uncu, D; Zengin, N, 2010)	0.36
"Both BP and B seems to be effective and safe regimens for patients with PS or platinum-resistant recurrent ovarian cancer."	( Efficacy and toxicity of belotecan with and without cisplatin in patients with recurrent ovarian cancer. Jang, SY; Jung, YW; Kim, JH; Kim, JW; Kim, S; Kim, SW; Kim, YT; Lee, DW; Nam, EJ, 2010)	0.36
" This suggests that the bilirubin level may be an indicator of the adverse effects caused by CPT- 11."	( [Assessment of total bilirubin or SN-38/SN-38G ratio as a predictor of severe irinotecan toxicity]. Harada, M; Isobe, H; Izumi, K; Mino, K; Saito, K; Tanaka, H, 2009)	0.35
" The primary toxicity outcome measure was toxicity-induced delay or dose reduction; the secondary outcome was Common Terminology Criteria of Adverse Events grade >or= 3 toxicity."	( Association of molecular markers with toxicity outcomes in a randomized trial of chemotherapy for advanced colorectal cancer: the FOCUS trial. Adlard, JW; Allan, JM; Braun, MS; Daly, CL; Meade, AM; Parmar, MK; Quirke, P; Richman, SD; Seymour, MT; Thompson, L, 2009)	0.35
" Propolis preparation and related flavonoids were found to exhibit an important immunomodulatory effect and could decrease irinotecan-induced toxic and genotoxic effects to normal cells without effecting irinotecan cytotoxicity in EAT cells."	( Protective effects of propolis and related polyphenolic/flavonoid compounds against toxicity induced by irinotecan. Benković, V; Dikić, D; Erhardt, J; Knežević, AH; Lisičić, D; Oršolić, N, 2010)	0.36
"FOLFOXIRI confers significant benefit in progression-free survival, survival, response and R0 resection rates but is more toxic compared with FOLFIRI."	( A systematic review of FOLFOXIRI chemotherapy for the first-line treatment of metastatic colorectal cancer: improved efficacy at the cost of increased toxicity. Chiriatti, A; Fiorentini, G; Francini, G; Montagnani, F; Turrisi, G, 2011)	0.37
" Secondly, the efficacy and safety disparity of clopidogrel, statins and irinotecan each among races and genetic variants are discussed to illustrate that pharmacogenetic knowledge is important for the interpretation and prediction of drug interaction-induced adverse events, whereas drug interaction -induced adverse events are equally informative for identifying genes-based mechanisms involved."	( Ongoing challenges in drug interaction safety: from exposure to pharmacogenomics. Bai, JP, 2010)	0.36
"The addition of cetuximab to chronotherapy allowed safe and effective therapeutic control of metastases, including their complete resection, despite previous failure of several treatment regimens."	( Cetuximab and circadian chronomodulated chemotherapy as salvage treatment for metastatic colorectal cancer (mCRC): safety, efficacy and improved secondary surgical resectability. Adam, R; Bouchahda, M; Giacchetti, S; Gorden, L; Guettier, C; Hauteville, D; Innominato, PF; Karaboué, A; Lévi, F; Saffroy, R, 2011)	0.37
" Patients treated with irinotecan occasionally experience severe neutropenia and delayed diarrhea, and the occurrence of these adverse reactions is unpredictable and still largely unexplained."	( Pharmacogenetics of irinotecan disposition and toxicity: a review. Fujita, K; Sparreboom, A, 2010)	0.36
"The progression-free rates confirm that cetuximab q2w in combination with irinotecan is an option, and is as active and safe as the standard weekly regimen."	( Cetuximab given every 2 weeks plus irinotecan is an active and safe option for previously treated patients with metastatic colorectal cancer. Alonso, V; Antón, I; Arrivi, A; Cirera, L; Constenla, M; Escudero, P; García, P; Grande, C; Guasch, I; López, LJ; Losa, F; Martin, C; Méndez, M; Moreno, I; Pericay, C; Quintero-Aldana, G; Roca, JM; Salud, A; Vicente, P; Yubero, A, 2010)	0.36
" The main adverse effects associated with the treatment included leucopenia, nausea/vomiting and peripheral neuritis."	( [Short-term therapeutic effect and safety of endostar combined with XELIRI regimen in the treatment of advanced colorectal cancer]. Liao, WJ; Luo, RC; Shen, P; Shi, M; Wu, Wy, 2010)	0.36
"Endostar combined with XELIRI is effective and safe as the second-line treatment for advanced colorectal cancer, and further clinical investigation is warranted."	( [Short-term therapeutic effect and safety of endostar combined with XELIRI regimen in the treatment of advanced colorectal cancer]. Liao, WJ; Luo, RC; Shen, P; Shi, M; Wu, Wy, 2010)	0.36
"Are plants always immune to their endogenous toxic secondary metabolites? Without disturbance, fast-growing Camptotheca plants can avoid poison by its endogenous camptothecin (DNA topoisomerase I inhibitor) at more than 10 times higher than the fatal concentration of exogenous application to the plant."	( Induced endogenous autotoxicity in Camptotheca. Li, S; Wang, P; Yuan, W, 2010)	0.56
" The most common adverse effect of belotecan was hematologic toxicity which was tolerable."	( The efficacy and toxicity of belotecan (CKD-602), a camptothericin analogue topoisomerase I inhibitor, in patients with recurrent or refractory epithelial ovarian cancer. Kim, DY; Kim, JH; Kim, YM; Kim, YT; Lee, SW; Nam, JH, 2010)	0.36
" Previous studies have reported the toxic effects of the test article following repeated IV dosing of CKD-602, a novel camptothecin-derivative anti-tumor agent that was developed by Chong Kun Dang Pharmaceutical Corporation in Seoul, Korea."	( Toxicity study of a new camptothecin anti-cancer agent CKD-602 in dogs: 4-week continuous intravenous dose by infusion pump and 4-week repeated intravenous dose. Han, EH; Han, SC; Hwang, IC; Kim, CY; Kim, DG; Kim, YB, 2010)	0.88
" There were 35 patients (19%) with irinotecan treatments who sustained 158 treatment-related adverse events, with the median CTCAE event grade being CTCAE grade 2 (range 1 to 5)."	( Toxicity of irinotecan-eluting beads in the treatment of hepatic malignancies: results of a multi-institutional registry. Bosnjakovic, PM; Howard, J; Martin, RC; Padr, R; Robbins, K; Tatum, C; Tomalty, D, 2010)	0.36
"DEBIRI is safe when appropriate technique and treatment are used."	( Toxicity of irinotecan-eluting beads in the treatment of hepatic malignancies: results of a multi-institutional registry. Bosnjakovic, PM; Howard, J; Martin, RC; Padr, R; Robbins, K; Tatum, C; Tomalty, D, 2010)	0.36
" It is essential to establish an efficient and safe protocol for the administration of camptothecin versus tumor metastasis and growth."	( The antitumor and antimetastatic effects of N-trimethyl chitosan-encapsulated camptothecin on ovarian cancer with minimal side effects. Chen, X; Du, L; He, X; Li, X; Li, Z; Qian, Z; Wei, Y; Wen, Y; Zhao, X; Zhou, L, 2010)	0.81
" No hematologic or non-hematologic toxic effects were clearly related to UGT1A1*1/*6 or *1/*28 during the first cycle or throughout the entire course of chemotherapy."	( UGT1A1*1/*28 and *1/*6 genotypes have no effects on the efficacy and toxicity of FOLFIRI in Japanese patients with advanced colorectal cancer. Akiyama, Y; Ando, Y; Araki, K; Fujita, K; Hirose, T; Ichikawa, W; Ishida, H; Kawara, K; Miwa, K; Miya, T; Mizuno, K; Nagashima, F; Narabayashi, M; Saji, S; Sasaki, Y; Sunakawa, Y; Yamamoto, W; Yamashita, K, 2011)	0.37
"The dose-limiting side effect of the common colon cancer chemotherapeutic CPT-11 is severe diarrhea caused by symbiotic bacterial β-glucuronidases that reactivate the drug in the gut."	( Alleviating cancer drug toxicity by inhibiting a bacterial enzyme. Jobin, C; Koo, JS; Lane, KT; Mani, S; Orans, J; Redinbo, MR; Scott, JE; Venkatesh, M; Wallace, BD; Wang, H; Yeh, LA, 2010)	0.36
" The incidences of grade 3 or 4 adverse events and grade 2 or greater histopathological sinusoidal injury were significantly higher in the SVI ≥ +30% than in the SVI < +30% group."	( Splenomegaly in FOLFOX-naïve stage IV or recurrent colorectal cancer patients due to chemotherapy-associated hepatotoxicity can be predicted by the aspartate aminotransferase to platelet ratio before chemotherapy. Arai, T; Kobayashi, S; Koike, J; Koizumi, S; Makizumi, R; Miura, K; Miyajima, N; Nakano, H; Otsubo, T; Sakurai, J; Shimamura, T; Yamada, K, 2011)	0.37
" Adverse events were assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events."	( Retrospective cohort study on the safety and efficacy of bevacizumab with chemotherapy for metastatic colorectal cancer patients: the HGCSG0801 study. Asaka, M; Hatanaka, K; Hosokawa, A; Iwanaga, I; Kato, T; Komatsu, Y; Kusumi, T; Miyagishima, T; Nakamura, M; Sakata, Y; Sogabe, S; Yuki, S, 2011)	0.37
" No severe adverse effects of more than grade 3 were encountered."	( [Palliative anti-cancer chemotherapy is safely executable in a hemodialytic patient with unresectable advanced gastric cancer]. Hosojima, Y; Miura, T; Nakamura, J; Nakazawa, Y; Ozeki, Y; Takahashi, T; Yamada, S; Yamazaki, H; Yanagi, M, 2011)	0.37
" End points included progression-free survival (PFS), overall survival (OS), response rate (RR), and grade 3 or worse adverse events."	( Impact of young age on treatment efficacy and safety in advanced colorectal cancer: a pooled analysis of patients from nine first-line phase III chemotherapy trials. Blanke, CD; Bleyer, A; Bot, BM; de Gramont, A; Goldberg, RM; Kohne, CH; Sargent, DJ; Seymour, MT; Thomas, DM, 2011)	0.37
" No febrile neutropenia or toxic death was recorded."	( Cisplatin and irinotecan combination chemotherapy for advanced thymic carcinoma: evaluation of efficacy and toxicity. Hosomi, Y; Iguchi, M; Okamura, T; Okuma, Y; Shibuya, M; Takagi, Y, 2011)	0.37
" The adverse effects observed were grade 3 in 7 patients(20."	( [Clinical efficacy and safety of CPT-11+CDDP therapy as third-line chemotherapy for advanced and recurrent gastric cancer]. Fujii, S; Fukahori, M; Godai, TI; Imada, T; Kunisaki, C; Makino, H; Masuda, M; Numata, M; Oshima, T; Rino, Y; Sato, T, 2011)	0.37
" Pharmacokinetics, the first area of investigation, has identified markers such as biliary index, the relative extent of conversion and the glucuronidation ratio, which are capable to define the risk for severe adverse effects."	( Pharmacokinetic and pharmacogenetic predictive markers of irinotecan activity and toxicity. Bocci, G; Danesi, R; Del Re, M; Di Desidero, T; Di Paolo, A; Lastella, M; Polillo, M, 2011)	0.37
" We investigated whether there might be a discrepancy between the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) and the Neurotoxicity Criteria of Debiopharm (DEB-NTC), the commonly used oxaliplatin-specific scales, in the evaluation of peripheral neurotoxicity."	( Discrepancy between the NCI-CTCAE and DEB-NTC scales in the evaluation of oxaliplatin-related neurotoxicity in patients with metastatic colorectal cancer. Inoue, N; Ishibashi, K; Ishida, H; Kishino, T; Kumamoto, K; Okada, N; Sano, M, 2012)	0.38
" The time of reccurrence and adverse effects were recorded."	( [Evaluation of the efficacy and safety of intravesical instillation with gemcitabine after first-line intravesical chemotherapy failure in the treatment of non-muscle-invasive bladder cancer]. Cao, M; Chen, HG; Ma, CK; Ma, J; Xue, W, 2011)	0.37
" Grades 3 and 4 adverse events included diarrhea (21% in the mIFL group and 26% in the bevacizumab plus mIFL group) and neutropenia (19% in the mIFL group and 33% in the bevacizumab plus mIFL group)."	( Efficacy and safety of bevacizumab plus chemotherapy in Chinese patients with metastatic colorectal cancer: a randomized phase III ARTIST trial. Ba, Y; Feng, FY; Guan, ZZ; He, J; Liang, J; Luo, RC; Qi, C; Qin, SK; Shen, L; Wang, D; Wang, JJ; Wang, LW; Xu, JM; Xu, RH; Yu, SY, 2011)	0.37
" In cats injected with irinotecan DEBs, such local adverse side effects did not occur."	( A safety and toxicity assessment of the administration of multiple intracerebral injections of irinotecan or doxorubicin drug-eluting beads. Brinker, T; Glage, S; Hedrich, HJ; Held, N; Lewis, AL, 2011)	0.37
" Although skin toxicities are the most common adverse events associated with EGFR inhibitors, the differences in efficacy and safety between pre-emptive and reactive skin treatment according to KRAS tumor status has not been reported."	( The efficacy and safety of panitumumab administered concomitantly with FOLFIRI or Irinotecan in second-line therapy for metastatic colorectal cancer: the secondary analysis from STEPP (Skin Toxicity Evaluation Protocol With Panitumumab) by KRAS status. Iannotti, N; Lacouture, ME; Mitchell, EP; Pillai, MV; Piperdi, B; Shearer, H; Xu, F; Yassine, M, 2011)	0.37
" The most commonly observed adverse events by KRAS tumor status included dermatitis acneiform and pruritus."	( The efficacy and safety of panitumumab administered concomitantly with FOLFIRI or Irinotecan in second-line therapy for metastatic colorectal cancer: the secondary analysis from STEPP (Skin Toxicity Evaluation Protocol With Panitumumab) by KRAS status. Iannotti, N; Lacouture, ME; Mitchell, EP; Pillai, MV; Piperdi, B; Shearer, H; Xu, F; Yassine, M, 2011)	0.37
"FOLFIRI-B may be an efficient and safe choice in the 2nd line treatment of patients with MCRC previously treated with oxaliplatin."	( Safety and efficacy of FOLFIRI-bevacizumab for metastatic colorectal carcinoma as second line treatment. Abali, H; Babacan, AN; Civelek, B; Dogan, U; Isik, M; Kos, T; Odabas, H; Oksuzoglu, B; Ozdemir, N; Zengin, N, )	0.13
"Toxicogenomics, based on the temporal effects of drugs on gene expression, is able to predict toxic effects earlier than traditional technologies by analyzing changes in genomic biomarkers that could precede subsequent protein translation and initiation of histological organ damage."	( High-density real-time PCR-based in vivo toxicogenomic screen to predict organ-specific toxicity. Bito, T; Fabian, G; Farago, N; Feher, LZ; Katona, RL; Kitajka, K; Kulin, S; Nagy, LI; Puskas, LG; Tiszlavicz, L; Tubak, V, 2011)	0.37
" Relationships between genetic variants and adverse events, tumour response, overall and disease-free survivals were assessed."	( Methylenetetrahydrofolate reductase genetic polymorphisms and toxicity to 5-FU-based chemoradiation in rectal cancer. Alyasiri, A; Dvorak, A; Fleshman, JW; Hoskins, JM; McLeod, HL; Motsinger-Reif, AA; Myerson, RJ; Roy, S; Tan, BR; Thomas, F, 2011)	0.37
" However, the adverse effects associated with the treatment have hindered the efficacies of irinotecan."	( Ugt1a is required for the protective effect of selenium against irinotecan-induced toxicity. Cao, S; Durrani, FA; Rustum, YM; Yu, YE, 2012)	0.38
" The definition of a safe future liver remnant (FLR) volume based on preoperative clinical data in these patients is lacking."	( What is a safe future liver remnant size in patients undergoing major hepatectomy for colorectal liver metastases and treated by intensive preoperative chemotherapy? Bachellier, P; Chenard, MP; Fuchshuber, P; Jaeck, D; Narita, M; Nobili, C; Oussoultzoglou, E; Pessaux, P; Rosso, E, 2012)	0.38
"This study provides a cutoff FLR ratio for safe postoperative outcome after major hepatectomy in CLM patients receiving six or more cycles of preoperative chemotherapy."	( What is a safe future liver remnant size in patients undergoing major hepatectomy for colorectal liver metastases and treated by intensive preoperative chemotherapy? Bachellier, P; Chenard, MP; Fuchshuber, P; Jaeck, D; Narita, M; Nobili, C; Oussoultzoglou, E; Pessaux, P; Rosso, E, 2012)	0.38
" Most commonly reported grade-3 or -4 adverse events included neutropenia (54%), thrombocytopenia (38%), and anemia (32%)."	( Efficacy and toxicity of belotecan for relapsed or refractory small cell lung cancer patients. Ae Kang, Y; Cho, BC; Hong, YK; Jeong, JH; Kim, GM; Kim, JH; Kim, SK; Kim, SM; Kim, YS; Lim, ST; Sung, JH, 2012)	0.38
"Skin toxicity is a frequent adverse event of epidermal growth factor receptor (EGFR) targeting agents."	( Prognostic value of cetuximab-related skin toxicity in metastatic colorectal cancer patients and its correlation with parameters of the epidermal growth factor receptor signal transduction pathway: results from a randomized trial of the GERMAN AIO CRC Stu Giessen, C; Heinemann, V; Jung, A; Kapaun, C; Kirchner, T; Laubender, RP; Modest, DP; Moosmann, N; Neumann, J; Stintzing, S; Wollenberg, A, 2013)	0.39
" Plasma concentration data and adverse effects were modeled using the population approach."	( Population pharmacokinetic/pharmacodynamic modeling of drug-induced adverse effects of a novel homocamptothecin analog, elomotecan (BN80927), in a Phase I dose finding study in patients with advanced solid tumors. Cendrós, JM; Cvitkovic, F; Delavault, P; Lesimple, T; Obach, R; Peraire, C; Perez-Mayoral, A; Principe, P; Pruñonosa, J; Soto, E; Trocóniz, IF, 2012)	0.6
"Sequential IRIS + bevacizumab is a safe and effective method of systemic chemotherapy against metastatic colorectal cancer and is compatible with mFOLFIRI + bevacizumab."	( Safety verification trials of mFOLFIRI and sequential IRIS + bevacizumab as first- or second-line therapies for metastatic colorectal cancer in Japanese patients. Akiyama, S; Andoh, H; Gamoh, M; Ishioka, C; Kato, S; Maeda, S; Mori, T; Murakawa, Y; Ohori, H; Sasaki, Y; Shimodaira, H; Suzuki, T; Takahashi, S; Yamaguchi, T; Yoshioka, T, 2012)	0.38
" FOLFIRI regimen is safe and effective in the second-line treatment of AGC patients pre-treated with cisplatin and taxanes."	( The efficacy and toxicity of irinotecan with leucovorin and bolus and continuous infusional 5-fluorouracil (FOLFIRI) as salvage therapy for patients with advanced gastric cancer previously treated with platinum and taxane-based chemotherapy regimens. Alkis, N; Arpacı, E; Benekli, M; Berk, V; Bilici, A; Budakoglu, B; Buyukberber, S; Coskun, U; Dane, F; Demirci, U; Gumus, M; Inal, A; Isıkdogan, A; Kaya, AO; Ozkan, M; Yumuk, F, 2012)	0.38
" Major grade 3/4 adverse events included neutropenia (28."	( Uridine diphosphate glucuronosyl transferase 1 family polypeptide A1 gene (UGT1A1) polymorphisms are associated with toxicity and efficacy in irinotecan monotherapy for refractory pancreatic cancer. Hamada, T; Hirano, K; Ijichi, H; Isayama, H; Kawakubo, K; Kogure, H; Koike, K; Miyabayashi, K; Mizuno, S; Mohri, D; Nakai, Y; Sasahira, N; Sasaki, T; Satoh, Y; Tada, M; Takahara, N; Takai, D; Uchino, R; Yamamoto, N; Yatomi, Y, 2013)	0.39
" The active form of CPT-11, SN-38, causes the adverse events such as neutropenia and diarrhea."	( Polymorphisms of the UDP-glucuronosyl transferase 1A genes are associated with adverse events in cancer patients receiving irinotecan-based chemotherapy. Etoh, T; Hayashi, H; Inoue, K; Itoh, K; Kawamura, Y; Kikuyama, M; Kimura, M; Matsumura, T; Minami, S; Sonobe, M; Suzuki, T; Takagi, M; Tsuji, D; Utsuki, H; Yamazaki, T, 2013)	0.39
" The use of combined neoadjuvant chemotherapy is safe before hepatic resection."	( Bevacizumab treatment before resection of colorectal liver metastases: safety, recovery of liver function, pathologic assessment. Baranyai, ZS; Besznyák, I; Bursics, A; Dede, K; Jakab, F; Landherr, L; Mersich, T; Salamon, F; Zaránd, A, 2013)	0.39
"Camptothecin (CPT), a plant alkaloid originally isolated from the native Chinese tree, Camptotheca acuminate, exerts the toxic effect by targeting eukaryotic DNA topoisomerase 1 (DNA Topo1)."	( Characterization of DNA topoisomerase-1 in Spodoptera exigua for toxicity evaluation of camptothecin and hydoxy-camptothecin. He, W; Jiang, H; Li, C; Ma, D; Yang, J; Zhang, L; Zhang, Y, 2013)	2.05
" Grade 3/4 diarrhea as predominant toxic effect occurred in 22% of patients with CapOx-bevacizumab and in 16% with mCapIri-bevacizumab."	( Capecitabine/irinotecan or capecitabine/oxaliplatin in combination with bevacizumab is effective and safe as first-line therapy for metastatic colorectal cancer: a randomized phase II study of the AIO colorectal study group. Arnold, D; Dietrich, G; Freier, W; Geißler, M; Graeven, U; Hegewisch-Becker, S; Hinke, A; Kubicka, S; Pohl, M; Reinacher-Schick, A; Schmiegel, W; Schmoll, HJ; Tannapfel, A, 2013)	0.39
"Both, CapOx-bevacizumab and mCapIri-bevacizumab, show promising activity and an excellent toxic effect profile."	( Capecitabine/irinotecan or capecitabine/oxaliplatin in combination with bevacizumab is effective and safe as first-line therapy for metastatic colorectal cancer: a randomized phase II study of the AIO colorectal study group. Arnold, D; Dietrich, G; Freier, W; Geißler, M; Graeven, U; Hegewisch-Becker, S; Hinke, A; Kubicka, S; Pohl, M; Reinacher-Schick, A; Schmiegel, W; Schmoll, HJ; Tannapfel, A, 2013)	0.39
"This analysis was conducted to clarify risk factors for severe adverse effects and treatment-related deaths reported during a postmarketing survey of irinotecan."	( Risk factors for severe adverse effects and treatment-related deaths in Japanese patients treated with irinotecan-based chemotherapy: a postmarketing survey. Boku, N; Fujiki, T; Fujino, K; Gemma, A; Kakihata, K; Masatani, S; Morita, S; Shiozawa, T; Tadokoro, J, 2013)	0.39
" The patient background data and adverse drug reactions were collected through case report forms."	( Risk factors for severe adverse effects and treatment-related deaths in Japanese patients treated with irinotecan-based chemotherapy: a postmarketing survey. Boku, N; Fujiki, T; Fujino, K; Gemma, A; Kakihata, K; Masatani, S; Morita, S; Shiozawa, T; Tadokoro, J, 2013)	0.39
" Major grade 3-4 adverse drug reactions were leukopenia (34."	( Risk factors for severe adverse effects and treatment-related deaths in Japanese patients treated with irinotecan-based chemotherapy: a postmarketing survey. Boku, N; Fujiki, T; Fujino, K; Gemma, A; Kakihata, K; Masatani, S; Morita, S; Shiozawa, T; Tadokoro, J, 2013)	0.39
" Biomarkers for predicting high-risk severe adverse reactions can help select the best treatment."	( Differential toxicity biomarkers for irinotecan- and oxaliplatin-containing chemotherapy in colorectal cancer. Cortejoso, L; Escolar, F; García, MI; García-Alfonso, P; González-Haba, E; López-Fernández, LA; Sanjurjo, M, 2013)	0.39
" The majority of the toxic manifestation is caused by the insufficient deactivation (glucuronidation) of irinotecan active metabolite SN-38 by UGT1A enzyme."	( Predictors of irinotecan toxicity and efficacy in treatment of metastatic colorectal cancer. Filip, S; Grim, J; Paulík, A, 2012)	0.38
" In vitro cell culture testing demonstrated that all formulations increased CPT potency compared to free CPT, while cationic formulations proved significantly more toxic to cancer cells that healthy cells."	( Investigation of parameters influencing incorporation, retention and cellular cytotoxicity in liposomal formulations of poorly soluble camptothecin. Flaten, GE; Ingebrigtsen, SG; Naderkhani, E; Skar, ML; Whitaker, RD, 2013)	0.59
"There have been no case reports of the risk of serious adverse events associated with the administration of irinotecan hydrochloride (CPT-11) in patients with gynecologic cancer who are compound heterozygous for UGT1A1*6 and UGT1A1*28."	( Recurrent cervical cancer in a patient who was compound heterozygous for UGT1A1*6 and UGT1A1*28 presenting with serious adverse events during irinotecan hydrochloride/nedaplatin therapy. Miura, Y; Shoji, T; Sugiyama, T; Takatori, E; Takeuchi, S; Yoshizaki, A, 2013)	0.39
"To investigate the correlation of MDR1 and ABCG2 genetic polymorphisms with the efficacy and adverse events of irinotecan chemotherapy in patients with colorectal cancer (CRC)."	( [Correlation of MDR1 and ABCG2 genetic polymorphisms with the efficacy and adverse events of irinotecan chemotherapy in patients with colorectal cancer]. Dang, YZ; Gao, J; Li, J; Li, YY; Shen, L; Sun, ZW; Wang, XC, 2013)	0.39
" Simultaneous heterozygous UGT1A1 28 and UGT1A1 6 polymorphisms may produce higher exposure to SN-38 and a higher risk of adverse effects related to irinotecan."	( Severe irinotecan-induced toxicity in a patient with UGT1A1 28 and UGT1A1 6 polymorphisms. Ge, FJ; Lin, L; Liu, ZY; Sharma, MR; Wang, Y; Xu, JM, 2013)	0.39
"At 5 centers, Cmab+CPT-11 was an effective and safe treatment after second-line therapy."	( [Efficacy and safety of cetuximab+irinotecan for unresectable advanced or recurrent colorectal cancer]. Akatsuka, S; Arioka, H; Azuma, T; Egawa, M; Hibi, K; Ito, T; Kenmochi, T; Koizumi, W; Nagashima, A; Nemoto, H; Sasaki, T; Shimada, K; Soda, H; Takinishi, Y, 2013)	0.39
"8) suggesting that the camptothecin regimen was synergistic and that the addition of sodium-R-alpha lipoate was important for reducing the camptothecin dose and potential for adverse effects."	( Selective cytotoxicity and combined effects of camptothecin or paclitaxel with sodium-R-alpha lipoate on A549 human non-small cell lung cancer cells. Gao, D; Ibrahim, S; Sinko, PJ, 2014)	0.97
" Here, we investigated the prevalence of three different variants of UGT1A1 (UGT1A1*6, UGT1A1*27 and UGT1A1*28) and their relationships with irinotecan-induced adverse events in patients with gynecologic cancer, who are treated with lower doses of irinotecan than patients with other types of solid tumors."	( Polymorphisms in the UGT1A1 gene predict adverse effects of irinotecan in the treatment of gynecologic cancer in Japanese patients. Akahane, T; Aoki, D; Hirasawa, A; Kataoka, F; Kosaki, K; Makita, K; Nomura, H; Okubo, K; Saito, K; Susumu, N; Tanigawara, Y; Tominaga, E; Zama, T, 2013)	0.39
" Acting as chemopotentiators, the studied excipients could have potential in reducing therapeutic HCPT doses and minimizing adverse effects in lung and colon chemotherapy."	( Augmented cytotoxicity of hydroxycamptothecin-loaded nanoparticles in lung and colon cancer cells by chemosensitizing pharmaceutical excipients. Zaki, NM, 2014)	0.68
" Recognizing this self-limiting toxic effect of oxaliplatin is important in order to avoid dose reductions that may affect clinical outcomes."	( A curious case of oxaliplatin-induced neurotoxicity: recurrent, self-limiting dysarthria. Dasanu, CA; Joseph, R, 2014)	0.4
"TLC388 at 50 mg/m(2) on the current treatment schedule is generally safe and well tolerated."	( A phase 1 open-label, sequential dose-escalation study investigating the safety, tolerability, and pharmacokinetics of intravenous TLC388 administered to patients with advanced solid tumors. Cheng, AL; Cho, DC; Chuadhary, I; Coleman, T; Ghalib, MH; Ghamande, S; Goel, S; Hsu, SC; Kuo, MW; Kwak, EL; Lin, CC; Mach, WB; Shapiro, GI; Silverman, MH; Tseng, Y; Yang, JC, 2014)	0.4
"Cardiac toxicity an uncommon but serious side-effect of some fluoropyrimides."	( Final results of Australasian Gastrointestinal Trials Group ARCTIC study: an audit of raltitrexed for patients with cardiac toxicity induced by fluoropyrimidines. Ferry, D; Fournier, M; Gebski, V; Gordon, S; Karapetis, CS; Price, TJ; Ransom, D; Simes, RJ; Tebbutt, N; Wilson, K; Yip, D, 2014)	0.4
" Raltitrexed, alone or in combination with oxaliplatin or irinotecan, provides a safe option in terms of cardiac toxicity for such patients."	( Final results of Australasian Gastrointestinal Trials Group ARCTIC study: an audit of raltitrexed for patients with cardiac toxicity induced by fluoropyrimidines. Ferry, D; Fournier, M; Gebski, V; Gordon, S; Karapetis, CS; Price, TJ; Ransom, D; Simes, RJ; Tebbutt, N; Wilson, K; Yip, D, 2014)	0.4
" The clinical efficacy and bevacizumab-related adverse reactions were observed."	( [Efficacy and safety of bevacizumab (BEV) plus chemotherapeutic agents in the treatment of metastatic colorectal cancer, mCRC]. Chen, Y; Cui, YH; Guo, X; Liu, TS; Yu, YY; Zhou, YH; Zhuang, RY, 2013)	0.39
" However, he experienced adverse effects, and subsequently, he was effectively treated with cisplatin (CDDP) and irinotecan (CPT-11)."	( [An effective treatment by chemotherapy with CDDP+CPT-11 for recurrent gastric cancer which S-1 cannot be used owing to adverse effects]. Aoyagi, H; Hasegawa, K; Isogai, J; Kaneko, J; Maejima, S; Matsui, T; Yoshida, T, 2013)	0.39
" CPT-11 causes toxic side-effects in patients."	( The role of intestinal microbiota in development of irinotecan toxicity and in toxicity reduction through dietary fibres in rats. Baracos, V; Dieleman, L; Farhangfar, A; Gänzle, MG; Lin, XB; Sawyer, MB; Schieber, A; Valcheva, R, 2014)	0.4
"0144) adverse effects in stage II/III patients."	( Personalized dosing via pharmacokinetic monitoring of 5-fluorouracil might reduce toxicity in early- or late-stage colorectal cancer patients treated with infusional 5-fluorouracil-based chemotherapy regimens. Beachler, C; El-Deiry, WS; Harvey, HA; Kline, CL; Mackley, HB; McKenna, K; Messaris, E; Poritz, L; Schiccitano, A; Sheikh, H; Sivik, J; Staveley-O'Carroll, K; Stewart, D; Zhu, J, 2014)	0.4
"We have planned a multicentre prospective study to examine the relative impact of the efficacy and adverse events of cetuximab plus first-line chemotherapy on the quality of life in Japanese patients with KRAS wild-type unresectable colorectal cancer."	( A prospective observational study to examine the relationship between quality of life and adverse events of first-line chemotherapy plus cetuximab in patients with KRAS wild-type unresectable metastatic colorectal cancer: QUACK Trial. Ando, M; Fujii, H; Ooki, A; Sakamoto, J; Sato, A; Yamaguchi, K, 2014)	0.4
"Chemotherapy-induced diarrhea (CID) is a common and often severe side effect experienced by colorectal cancer (CRC) patients during their treatment."	( Gastro-intestinal toxicity of chemotherapeutics in colorectal cancer: the role of inflammation. Doherty, GA; Lee, CS; Ryan, EJ, 2014)	0.4
" A series of adverse events were comparable between two arms, whereas some of the antibody therapy-associated toxicities were observed in FOLFIRI+PB arm."	( Safety and efficacy of second-line treatment with folinic acid, 5-fluorouracil and irinotecan (FOLFIRI) in combination of panitumumab and bevacizumab for patients with metastatic colorectal cancer. Fan, Z; Han, G; He, L; Qin, Z; Xie, S; Xu, W, 2014)	0.4
"Many drugs are associated with variable response rates and, of the 1,200 drugs approved for use in the United States, about 15% are associated with adverse drug responses (Jorde, Carey, & Bamshad, 2010c)."	( Allelic expression of phase II metabolizing enzymes and relationship to irinotecan toxicity. Tadje, M, 2014)	0.4
" In xenograft models, 9a demonstrated significant activity without overt adverse effects at 5 and 10 mg/kg, comparable to 3 at 100 mg/kg."	( Design, synthesis, mechanisms of action, and toxicity of novel 20(s)-sulfonylamidine derivatives of camptothecin as potent antitumor agents. Chang, LC; Goto, M; Hung, HY; Kuo, DH; Kuo, SC; Lee, KH; Liu, YQ; Morris-Natschke, SL; Nan, X; Pan, SL; Qian, K; Teng, CM; Wang, CY; Wang, MJ; Wu, TS; Wu, YC; Yang, JS; Yang, L; Yang, XM; Zhao, XB; Zhao, YL, 2014)	0.62
" In vivo experiment showed Nano Se at a dose of 4 mg/kg/day significantly alleviated adverse effects induced by irinotecan (60 mg/kg) treatment."	( Cytotoxicity and therapeutic effect of irinotecan combined with selenium nanoparticles. Cai, P; Gao, F; Gao, L; Gao, X; Huang, G; Liang, J; Liu, R; Wang, Y; Wei, Y; Yuan, Q; Zhu, H, 2014)	0.4
" The incidence of adverse events was 70."	( Efficacy and safety of irinotecan plus S-1 (IRIS) therapy to treat advanced/recurrent colorectal cancer. Abe, S; Egawa, Y; Futami, K; Higashi, D; Hirano, K; Hirano, Y; Inoue, R; Maekawa, T; Mikami, K; Miyake, T; Miyazaki, M; Takahashi, H; Uwatoko, S; Yamamoto, S, 2014)	0.4
" IRIS therapy had a low incidence of serious adverse events and allowed patients to continue therapy on an out-patient basis."	( Efficacy and safety of irinotecan plus S-1 (IRIS) therapy to treat advanced/recurrent colorectal cancer. Abe, S; Egawa, Y; Futami, K; Higashi, D; Hirano, K; Hirano, Y; Inoue, R; Maekawa, T; Mikami, K; Miyake, T; Miyazaki, M; Takahashi, H; Uwatoko, S; Yamamoto, S, 2014)	0.4
" The comparison revealed no significant differences in response rate, progression-free survival, overall survival, and the frequency of overall adverse events after the start of second-line chemotherapy, although the frequency of anemia(Bgrade 3, p=0."	( [The efficacy and safety of FOLFIRI or combined FOLFIRI and bevacizumab treatment as second-line chemotherapy for metastatic colorectal cancer patients aged 75 years and older]. Baba, H; Chika, N; Haga, N; Ishibashi, K; Ishida, H; Kumagai, Y; Kumamoto, K; Okada, N; Sano, M; Tajima, Y, 2014)	0.4
" OBJECTIVE response rates (ORRs), progression-free survival (PFS), overall survival (OS) and adverse events were recorded, and the relationships between various clinical factors and PFS or OS were evaluated by Cox proportional hazards models."	( Efficacy and safety of bevacizumab in Chinese patients with metastatic colorectal cancer. Chen, L; Ju, HX; Liu, BX; Liu, LY; Luo, C; Xu, Q; Yang, YS; Ying, JE; Zhao, YZ; Zhong, HJ; Zhu, LM, 2014)	0.4
"The toxic effects of irinotecan are well understood."	( The power of genes: a case of unusually severe systemic toxicity after localized hepatic chemoembolization with irinotecan-eluted microspheres for metastatic colon cancer. Cruz, JE; Hermes-DeSantis, E; Jabbour, SK; Moss, RA; Nosher, JL; Saksena, R, 2014)	0.4
"Although genetic testing prior to the initiation of irinotecan therapy is not currently recommended, assessment of UGT1A1 polymorphism is warranted when severe adverse events typical of systemic therapy manifest following DEBIRI-TACE."	( The power of genes: a case of unusually severe systemic toxicity after localized hepatic chemoembolization with irinotecan-eluted microspheres for metastatic colon cancer. Cruz, JE; Hermes-DeSantis, E; Jabbour, SK; Moss, RA; Nosher, JL; Saksena, R, 2014)	0.4
"In 2594 patients with complete adverse event (AE) data, the incidence of grade 3 or greater 5FU-AEs in DPYD*2A, I560S, and D949V carriers were 22/25 (88."	( DPYD variants as predictors of 5-fluorouracil toxicity in adjuvant colon cancer treatment (NCCTG N0147). Alberts, SR; Berenberg, JL; Diasio, RB; Goldberg, RM; Lee, AM; Pavey, E; Sargent, DJ; Shi, Q; Sinicrope, FA, 2014)	0.4
"The aim was to investigate the association between uridine diphosphate glucuronide transferase 1A1 (UGT1A1) gene promoter region polymorphism and irinotecan-related adverse effects and efficacy on recurrent and refractory small cell lung cancer (SCLC)."	( Uridine diphosphate glucuronide transferase 1A1FNx0128 gene polymorphism and the toxicity of irinotecan in recurrent and refractory small cell lung cancer. Conghua, X; Haifeng, Y; Haiyan, Y; Lei, G; Lulu, M; Tao, L; Yun, F; Zhiyu, H, 2014)	0.4
" The efficacy and adverse effects of irinotecan were evaluated."	( Uridine diphosphate glucuronide transferase 1A1FNx0128 gene polymorphism and the toxicity of irinotecan in recurrent and refractory small cell lung cancer. Conghua, X; Haifeng, Y; Haiyan, Y; Lei, G; Lulu, M; Tao, L; Yun, F; Zhiyu, H, 2014)	0.4
"Irinotecan showed efficacy in patients with recurrent and refractory SCLC; UGT1A1 FNx01 28 polymorphism failed to predict the incidence of serious adverse effects and efficacy of irinotecan."	( Uridine diphosphate glucuronide transferase 1A1FNx0128 gene polymorphism and the toxicity of irinotecan in recurrent and refractory small cell lung cancer. Conghua, X; Haifeng, Y; Haiyan, Y; Lei, G; Lulu, M; Tao, L; Yun, F; Zhiyu, H, 2014)	0.4
"Modern anticancer chemotherapy can cause numerous adverse effects in the organism, whose functioning has already been disrupted by the neoplastic process itself."	( Evaluation of the toxicity of anticancer chemotherapy in patients with colon cancer. Filipczyk-Cisarż, E; Kowalska, T; Nartowski, K; Wiela-Hojeńska, A; Łapiński, Ł, )	0.13
"To prevent adverse drug reactions in the post-marketing phase, therapeutic drug monitoring and various laboratory tests have been used for decades."	( [Utilization of Genomic Biomarkers for Post-marketing Safety of Drugs]. Kaniwa, N, 2015)	0.42
" In conclusion, 3 days of fasting protects against the toxic side-effects of irinotecan in a clinically relevant mouse model of spontaneously developing colorectal cancer without affecting its anti-tumor activity."	( Fasting protects against the side effects of irinotecan but preserves its anti-tumor effect in Apc15lox mutant mice. Bijman-Lagcher, W; de Bruin, RW; Huisman, SA; IJzermans, JN; Smits, R, 2015)	0.42
"To assess the incidence and severity of adverse events (AEs) in the form of clinical symptoms and liver/biliary injuries (LBI) in patients with hepatic malignancies treated with transarterial chemoembolization using 70-150 μm drug-eluting beads (DEBs)."	( Transarterial hepatic chemoembolization with 70-150 µm drug-eluting beads: assessment of clinical safety and liver toxicity profile. Ashton, A; Gupta, S; Kaseb, A; Odisio, BC; Tam, AL; Vauthey, JN; Wallace, MJ; Wei, W; Yan, Y, 2015)	0.42
"Transarterial chemoembolization with 70-150 μm DEBs was considered safe in the present study population given the acceptably low incidence and severity of AEs."	( Transarterial hepatic chemoembolization with 70-150 µm drug-eluting beads: assessment of clinical safety and liver toxicity profile. Ashton, A; Gupta, S; Kaseb, A; Odisio, BC; Tam, AL; Vauthey, JN; Wallace, MJ; Wei, W; Yan, Y, 2015)	0.42
" Most grade ≥ 3 adverse events (AEs) were reported during the initial cycles of treatment."	( Aflibercept for metastatic colorectal cancer: safety data from the Spanish named patient program. Díaz de Corcuera, I; García de la Torre, M; Pérez Hoyos, MT; Salgado Fernández, M; Vidal Arbués, A, 2015)	0.42
"Chemotherapy-induced toxic liver injury is a relevant issue in the clinical management of patients affected with metastatic colorectal cancer (mCRC)."	( Liver toxicity in colorectal cancer patients treated with first-line FOLFIRI-containing regimen: a single institution experience. Fausti, V; Gallo, P; Imperatori, M; Picardi, A; Santini, D; Spalato Ceruso, M; Tonini, G; Vespasiani Gentilucci, U; Vincenzi, B, 2015)	0.42
" All patients experienced at least one grade 3 or higher adverse event: neutropenia (five patients, 83%), proteinuria (two patients; 33%) and anemia, thrombocytopenia and hypertension (one patient each, 17%)."	( Safety and Pharmacokinetics of Second-line Ramucirumab plus FOLFIRI in Japanese Patients with Metastatic Colorectal Carcinoma. Gao, L; Gotoh, M; Nasroulah, F; Ohtsu, A; Yamazaki, K; Yoshino, T; Yoshizuka, N, 2015)	0.42
" Weight and adverse side effects were recorded daily."	( Fasting protects against the side effects of irinotecan treatment but does not affect anti-tumour activity in mice. de Bruijn, P; de Bruin, RW; Ghobadi Moghaddam-Helmantel, IM; Huisman, SA; IJzermans, JN; Mathijssen, RH; Wiemer, EA, 2016)	0.43
" Fasting induced a lower systemic exposure to SN-38, which may explain the absence of adverse side effects, while tumour levels of SN-38 remained unchanged."	( Fasting protects against the side effects of irinotecan treatment but does not affect anti-tumour activity in mice. de Bruijn, P; de Bruin, RW; Ghobadi Moghaddam-Helmantel, IM; Huisman, SA; IJzermans, JN; Mathijssen, RH; Wiemer, EA, 2016)	0.43
"The combination of 5-fluorouracil (5-FU), irinotecan and oxaliplatin (FOLFIRINOX) is considered the first-line chemotherapy for fit patients with advanced pancreatic ductal adenocarcinoma (PDAC) but carries an unfavourable adverse event (AE) profile."	( Safety and Efficacy of Modified FOLFIRINOX for Advanced Pancreatic Adenocarcinoma: A UK Single-Centre Experience. Basu, B; Calder, J; Corrie, P; Ghorani, E; Hewitt, C; Wong, HH, 2015)	0.42
" The most common adverse event in both groups was diarrhea (Q3W 92."	( Safety, efficacy, and pharmacokinetics of navitoclax (ABT-263) in combination with irinotecan: results of an open-label, phase 1 study. Arzt, J; Busman, TA; Holen, KD; Lian, G; LoRusso, P; Rosen, LS; Rudersdorf, NS; Tolcher, AW; Vanderwal, CA; Waring, JF; Yang, J, 2015)	0.42
" All-grade adverse events occurred in 18 % of patients receiving prior systemic irinotecan compared with 15 % of patients receiving no prior systemic irinotecan (including chemo-naïve patients)."	( Efficacy and Toxicity of Hepatic Intra-Arterial Drug-Eluting (Irinotecan) Bead (DEBIRI) Therapy in Irinotecan-Refractory Unresectable Colorectal Liver Metastases. Akinwande, O; Bhutiani, N; Martin, RC, 2016)	0.43
" While DEBIRI complete response rates are greatest and overall adverse events are least in chemotherapy-naïve individuals, it retains its respectable efficacy and low rate of serious adverse events even in the setting of previous administration of systemic chemotherapy."	( Efficacy and Toxicity of Hepatic Intra-Arterial Drug-Eluting (Irinotecan) Bead (DEBIRI) Therapy in Irinotecan-Refractory Unresectable Colorectal Liver Metastases. Akinwande, O; Bhutiani, N; Martin, RC, 2016)	0.43
" The primary objective was to investigate the incidence of adverse drug reactions, particularly those of interest for bevacizumab."	( Bevacizumab safety in Japanese patients with colorectal cancer. Doi, T; Hatake, K; Ishihara, Y; Shirao, K; Takahashi, Y; Uetake, H, 2016)	0.43
"5%) were the most common adverse drug reaction."	( Bevacizumab safety in Japanese patients with colorectal cancer. Doi, T; Hatake, K; Ishihara, Y; Shirao, K; Takahashi, Y; Uetake, H, 2016)	0.43
" While the four-drug regimen, FOLFIRINOX (comprising irinotecan, 5-fluorouracil, oxaliplatin, and leucovorin), has a better survival outcome than the more frequently used gemcitabine, the former treatment platform is highly toxic and restricted for use in patients with good performance status."	( Irinotecan Delivery by Lipid-Coated Mesoporous Silica Nanoparticles Shows Improved Efficacy and Safety over Liposomes for Pancreatic Cancer. Chang, CH; Donahue, T; Kang, Y; Liao, Y; Liu, X; Meng, H; Nel, AE; Situ, A; Villabroza, KR, 2016)	0.43
" We evaluated treatment-related adverse events (AEs), progression-free survival (PFS) and overall survival (OS)."	( Safety and Management of Toxicity Related to Aflibercept in Combination with Fluorouracil, Leucovorin and Irinotecan in Malaysian Patients with Metastatic Colorectal Cancer. Abdullah, NM; Sharial, MM; Yusof, MM; Zaatar, A, 2016)	0.43
" All adverse events resolved with supportive management."	( Safety and efficacy of aflibercept in combination with fluorouracil, leucovorin and irinotecan in the treatment of Asian patients with metastatic colorectal cancer. Chong, DQ; Choo, SP; Chua, C; Imperial, M; Manalo, M; Ng, M; Tan, IB; Teo, P; Yong, G, 2016)	0.43
"Traditional methods of reporting adverse events in clinical trials are inadequate for modern cancer treatments with chronic administration."	( Longitudinal adverse event assessment in oncology clinical trials: the Toxicity over Time (ToxT) analysis of Alliance trials NCCTG N9741 and 979254. Atherton, PJ; Grothey, A; Loprinzi, CL; Novotny, PJ; Sloan, JA; Thanarajasingam, G, 2016)	0.43
"We developed an analytic approach and standardised, comprehensive format, the Toxicity over Time (ToxT) approach, which combines graphs and adverse event tabular displays with multiple longitudinal statistical techniques into a readily applicable method to study toxic effects."	( Longitudinal adverse event assessment in oncology clinical trials: the Toxicity over Time (ToxT) analysis of Alliance trials NCCTG N9741 and 979254. Atherton, PJ; Grothey, A; Loprinzi, CL; Novotny, PJ; Sloan, JA; Thanarajasingam, G, 2016)	0.43
"The ToxT analytical approach incorporates the dimension of time into adverse event assessment and offers a more comprehensive depiction of toxic effects than present methods."	( Longitudinal adverse event assessment in oncology clinical trials: the Toxicity over Time (ToxT) analysis of Alliance trials NCCTG N9741 and 979254. Atherton, PJ; Grothey, A; Loprinzi, CL; Novotny, PJ; Sloan, JA; Thanarajasingam, G, 2016)	0.43
"4% experienced grade 3/4 adverse events."	( Effectiveness and safety of first-line bevacizumab plus FOLFIRI in elderly patients with metastatic colorectal cancer: Results of the ETNA observational cohort. Becouarn, Y; Fourrier-Réglat, A; Grelaud, A; Guimbaud, R; Jové, J; Moore, N; Noize, P; Ravaud, A; Robinson, P; Rouyer, M; Smith, D; Tubiana-Mathieu, N, 2016)	0.43
"The present study adds to the literature on the safe and beneficial effect of bevacizumab in the elderly receiving FOLFIRI regimen."	( Effectiveness and safety of first-line bevacizumab plus FOLFIRI in elderly patients with metastatic colorectal cancer: Results of the ETNA observational cohort. Becouarn, Y; Fourrier-Réglat, A; Grelaud, A; Guimbaud, R; Jové, J; Moore, N; Noize, P; Ravaud, A; Robinson, P; Rouyer, M; Smith, D; Tubiana-Mathieu, N, 2016)	0.43
" The patients were followed up to analyze the relationship between different genotypes with adverse reactions and the clinical outcome of irinotecan-based chemotherapy."	( UGT1A1 gene polymorphism is associated with toxicity and clinical efficacy of irinotecan-based chemotherapy in patients with advanced colorectal cancer. Keyoumu, S; Qu, Y; Tang, X; Tang, Y; Xu, C; Zhou, N, 2016)	0.43
"UGT1A1 gene polymorphism predicts irinotecan-related adverse reactions in advanced CRC patients of Xinjiang Uygur and Han nationality; UGT1A1 gene polymorphism is correlated with efficacy and prognosis in Uygur nationality, but only related to prognosis in Han nationality in irinotecan-based chemotherapy."	( UGT1A1 gene polymorphism is associated with toxicity and clinical efficacy of irinotecan-based chemotherapy in patients with advanced colorectal cancer. Keyoumu, S; Qu, Y; Tang, X; Tang, Y; Xu, C; Zhou, N, 2016)	0.43
" The development of in vivo tools to study OATP1A/1B functions has greatly advanced our mechanistic understanding of their functional role in drug pharmacokinetics, and their implications for therapeutic efficacy and toxic side effects of anticancer and other drug treatments."	( The impact of Organic Anion-Transporting Polypeptides (OATPs) on disposition and toxicity of antitumor drugs: Insights from knockout and humanized mice. Durmus, S; Schinkel, AH; van Hoppe, S, 2016)	0.43
" The major grade 3 or 4 adverse events including neutropenia, fatigue, and anorexia were observed in 12 (24 %), 8 (16 %), and 7 (14 %), respectively."	( Efficacy and safety of irinotecan monotherapy as third-line treatment for advanced gastric cancer. Fukutomi, A; Hamauchi, S; Kawahira, M; Kawai, S; Kawakami, T; Kito, Y; Machida, N; Onozawa, Y; Todaka, A; Tsushima, T; Yamazaki, K; Yasui, H; Yokota, T; Yoshida, Y, 2016)	0.43
"Gastrointestinal toxicity is the most common adverse effect of chemotherapy."	( Intestinal permeability to iohexol as an in vivo marker of chemotherapy-induced gastrointestinal toxicity in Sprague-Dawley rats. Forsgård, RA; Frias, R; Holma, R; Korpela, R; Lindén, J; Österlund, P; Spillmann, T, 2016)	0.43
" The risk of mortality, therapeutic efficacy, and adverse effect were meta-analyzed."	( Efficacy and safety of addition of bevacizumab to FOLFIRI or irinotecan/bolus 5-FU/LV (IFL) in patients with metastatic colorectal cancer: A meta-analysis. Chen, K; Gong, Y; Shen, Y; Zhang, Q; Zhou, T, 2016)	0.43
" Main outcome measures included progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and adverse events."	( The efficacy and safety of panitumumab plus irrinotecan-based chemotherapy in the treatment of metastatic colorectal cancer: A meta-analysis. Chen, Q; Cheng, M; Wang, Z; Zhao, S, 2016)	0.43
" Moreover, combination therapy also induced an incidence of 56% treatment-related adverse events."	( The efficacy and safety of panitumumab plus irrinotecan-based chemotherapy in the treatment of metastatic colorectal cancer: A meta-analysis. Chen, Q; Cheng, M; Wang, Z; Zhao, S, 2016)	0.43
" As a consequence, two strategies have been developed in order to achieve safe and efficient delivery of camptothecin to target cells: structural analogues and nanomedicines."	( Safe approaches for camptothecin delivery: Structural analogues and nanomedicines. Botella, P; Rivero-Buceta, E, 2017)	0.99
" The most frequent grade 3/4 adverse events were nausea (18."	( Efficacy and Safety of FOLFIRINOX in Locally Advanced Pancreatic Cancer. A Single Center Experience. Bodoky, G; Harsanyi, L; Hegyi, P; Lakatos, G; Nehéz, L; Petranyi, A; Szűcs, A, 2017)	0.46
" Grade ≥ 3 adverse events included neutropenia (39%), leukopenia (16%), anemia (14%), and diarrhea (13%); the incidence of febrile neutropenia was 7%."	( Efficacy and Safety of Anti-Trop-2 Antibody Drug Conjugate Sacituzumab Govitecan (IMMU-132) in Heavily Pretreated Patients With Metastatic Triple-Negative Breast Cancer. Abramson, V; Bardia, A; Berlin, J; Diamond, JR; Goldenberg, DM; Govindan, SV; Guarino, M; Isakoff, SJ; Juric, D; Kalinsky, K; Maliakal, P; Mayer, IA; Messersmith, WA; Moroose, RL; O'Shaughnessy, J; Ocean, AJ; Shah, NC; Sharkey, RM; Starodub, AN; Tolaney, SM; Vahdat, LT; Wegener, WA, 2017)	0.46
" Finally, CN-CPT significantly inhibited the growth, the metastatization and the vascularization of orthotopic ATC xenografts in SCID/beige mice without apparent toxic effects in vivo."	( Enhanced cytotoxic effect of camptothecin nanosponges in anaplastic thyroid cancer cells in vitro and in vivo on orthotopic xenograft tumors. Annaratone, L; Argenziano, M; Barrera, G; Boggio, E; Boldorini, R; Cavalli, R; Chiocchetti, A; Clemente, N; Dianzani, C; Dianzani, U; Fantozzi, R; Ferrara, B; Gigliotti, CL; Giovarelli, M; Marchiò, C; Occhipinti, S; Pizzimenti, S; Trotta, F, 2017)	0.75
" With regard to the reasons for discontinuation of treatment, the Ram + PTX regimen had only one case of being discontinued owing to adverse events, and had a profile similar to that of the PTX and CPT-11 regimens."	( Cost-effectiveness and safety of ramucirumab plus paclitaxel chemotherapy in the treatment of advanced and recurrent gastric cancer. Kimura, M; Teramachi, H; Usami, E; Yoshimura, T, 2018)	0.48
" Treatment-emergent adverse events (AEs) were comparable for patients <65years and ≥65years old."	( Observed benefit and safety of aflibercept in elderly patients with metastatic colorectal cancer: An age-based analysis from the randomized placebo-controlled phase III VELOUR trial. Dochy, E; Lakomy, R; Macarulla, T; Magherini, E; Moiseyenko, VM; Papamichael, D; Prausova, J; Ruff, P; Soussan-Lazard, K; Van Cutsem, E; van Hazel, GA, 2018)	0.48
"Acne-like skin rash is a frequently occurring adverse event associated with drugs against the epidermal growth factor receptor."	( EVITA-a double-blind, vehicle-controlled, randomized phase II trial of vitamin K1 cream as prophylaxis for cetuximab-induced skin toxicity. Al-Batran, SE; Ettrich, TJ; Feustel, HP; Heeger, S; Hofheinz, RD; Homann, N; Kripp, M; Lorenzen, S; Merx, K; Ocvirk, J; Schatz, M; Schulte, N; Schulz, H; Tetyusheva, M; Trojan, J; Vlassak, S, 2018)	0.48
"The primary end point was the 10-month progression-free rate (PFR); secondary end points included progression-free and overall survival, response rate, rate of metastases resection, and adverse events."	( Activity and Safety of Cetuximab Plus Modified FOLFOXIRI Followed by Maintenance With Cetuximab or Bevacizumab for RAS and BRAF Wild-type Metastatic Colorectal Cancer: A Randomized Phase 2 Clinical Trial. Antoniotti, C; Aprile, G; Bergamo, F; Boni, L; Cardellino, GG; Coltelli, L; Corsi, DC; Cremolini, C; Dell'Aquila, E; Di Fabio, F; Falcone, A; Fontanini, G; Gemma, D; Grande, R; Lonardi, S; Lupi, C; Mancini, ML; Marcucci, L; Marmorino, F; Masi, G; Mescoli, C; Ronzoni, M; Salvatore, L; Tonini, G; Zagonel, V, 2018)	0.48
" Main grade 3/4 adverse events were neutropenia (occurring in 36 patients [31%]), diarrhea (in 21 patients [18%]), skin toxic effects (in 18 patients [16%]), asthenia (in 11 patients [9%]), stomatitis (in 7 patients [6%]), and febrile neutropenia (in 3 patients [3%])."	( Activity and Safety of Cetuximab Plus Modified FOLFOXIRI Followed by Maintenance With Cetuximab or Bevacizumab for RAS and BRAF Wild-type Metastatic Colorectal Cancer: A Randomized Phase 2 Clinical Trial. Antoniotti, C; Aprile, G; Bergamo, F; Boni, L; Cardellino, GG; Coltelli, L; Corsi, DC; Cremolini, C; Dell'Aquila, E; Di Fabio, F; Falcone, A; Fontanini, G; Gemma, D; Grande, R; Lonardi, S; Lupi, C; Mancini, ML; Marcucci, L; Marmorino, F; Masi, G; Mescoli, C; Ronzoni, M; Salvatore, L; Tonini, G; Zagonel, V, 2018)	0.48
" Treatment-emergent adverse events were reported in 97."	( Aflibercept Plus FOLFIRI in the Real-life Setting: Safety and Quality of Life Data From the Italian Patient Cohort of the Aflibercept Safety and Quality-of-Life Program Study. Antoniotti, C; Aprile, G; Bordonaro, R; Ciuffreda, L; Di Bartolomeo, M; Di Costanzo, F; Fasola, G; Frassineti, GL; Iaffaioli, V; Leone, F; Maiello, E; Marchetti, P; Pastorino, A; Sobrero, A; Zaniboni, A; Zilocchi, C, 2018)	0.48
" It did not affect HRQL and showed similar rates of treatment-emergent adverse events as those observed in the VELOUR trial."	( Aflibercept Plus FOLFIRI in the Real-life Setting: Safety and Quality of Life Data From the Italian Patient Cohort of the Aflibercept Safety and Quality-of-Life Program Study. Antoniotti, C; Aprile, G; Bordonaro, R; Ciuffreda, L; Di Bartolomeo, M; Di Costanzo, F; Fasola, G; Frassineti, GL; Iaffaioli, V; Leone, F; Maiello, E; Marchetti, P; Pastorino, A; Sobrero, A; Zaniboni, A; Zilocchi, C, 2018)	0.48
"Nanomedicines have achieved several breakthroughs in cancer treatment over the past decades; however, their potential immunotoxicities are ignored, which results in serious adverse effects and greatly reduces the potential in clinical translation."	( Supramolecular Polymer-Based Nanomedicine: High Therapeutic Performance and Negligible Long-Term Immunotoxicity. Chen, X; Gao, C; He, Z; Hua, B; Huang, F; Huang, X; Jacobson, O; Liu, Y; Mao, Z; Wang, W; Wang, Z; Yu, C; Yu, G; Zhang, F; Zhao, X; Zhou, J; Zhu, X, 2018)	0.48
" The concentration of the toxic metabolite, SN-38, was measured in the serum, and the activity of main enzyme, carboxylesterase (CEs) involved in biotransformation of irinotecan to SN-38 formation was measured in the liver."	( Impact of diet on irinotecan toxicity in mice. Gao, S; Ghose, R; Hu, M; Ittmann, MM; Mallick, P; Shah, P; Trivedi, M, 2018)	0.48
" Chemotherapy induced adverse reactions (neutropenia, diarrhea, nausea,\ vomiting, anorexia and infection) were recorded, and short-term effect of chemotherapy was evaluated regularly."	( Effects of Shengjiangxiexin decoction on irinotecan-induced toxicity in patients with UGT1A1*28 and UGT1A1*6 polymorphisms. Deng, B; Jia, L; Li, X; Li, Y; Lou, Y; Tan, H; Yu, L, 2017)	0.46
" There were no significant differences in any toxic effects\ (neutropenia, diarrhea, nausea, vomiting, anorexia or infection) between *6 or *28 variant patients\ (high risk group) and wild type patients."	( Effects of Shengjiangxiexin decoction on irinotecan-induced toxicity in patients with UGT1A1*28 and UGT1A1*6 polymorphisms. Deng, B; Jia, L; Li, X; Li, Y; Lou, Y; Tan, H; Yu, L, 2017)	0.46
" Main grade 3 or 4 adverse events in patients were neutropenia in 69 cases (22."	( [Analysis on safety and preliminary efficacy of dose-modified regimen of 5-fluorouracil plus oxaliplatin and irinotecan (FOLFOXIRI) in advanced colorectal cancer]. Cai, Y; Deng, R; Deng, Y; Hu, H; Li, J; Ling, J; Wu, Z; Yang, L; Zhang, J, 2018)	0.48
"Dose modification of chemotherapy for metastatic colorectal cancer (MCRC) is often needed, especially in second-line and later-line treatments due to adverse events of previous treatment and poor patient condition."	( Efficacy and safety of ramucirumab plus modified FOLFIRI for metastatic colorectal cancer. Aikawa, T; Akashi, K; Ariyama, H; Baba, E; Doi, Y; Esaki, T; Ito, M; Kobayashi, K; Kusaba, H; Makiyama, A; Mitsugi, K; Shimokawa, H; Takayoshi, K; Tsuchihashi, K; Uenomachi, M; Yoshihiro, T, 2019)	0.51
" These novel DDSs will help to achieve safe delivery of the very cytotoxic CPT, allowing to reduce the therapeutic dose and minimizing drug secondary effects."	( Amino modified metal-organic frameworks as pH-responsive nanoplatforms for safe delivery of camptothecin. Botella, P; Cabrera-García, A; Checa-Chavarria, E; Fernández, E; Moreno, V; Rivero-Buceta, E, 2019)	0.73
" Treatment-emergent adverse events (TEAEs) were evaluated, and HRQL was assessed at baseline, cycle 3, and every other cycle using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, EORTC QLQ-CR29, and EuroQol 5-Dimensions 3-Levels questionnaires (NCT01571284)."	( Aflibercept Plus FOLFIRI for Second-line Treatment of Metastatic Colorectal Cancer: Observations from the Global Aflibercept Safety and Health-Related Quality-of-Life Program (ASQoP). Aparicio, J; Bordonaro, R; Bury, D; Chau, I; Cicin, I; Di Bartolomeo, M; Drea, E; Fedyanin, MY; García-Alfonso, P; Heinemann, V; Karthaus, M; Kavan, P; Ko, YJ; Maiello, E; Martos, CF; Peeters, M; Picard, P; Riechelmann, RP; Sobrero, A; Srimuninnimit, V; Ter-Ovanesov, M; Yalcin, S, 2019)	0.51
" The studies demonstrated a significant benefit from the triplet at the price of an increased incidence of chemotherapy-related adverse events (AEs)."	( Impact of age and gender on the safety and efficacy of chemotherapy plus bevacizumab in metastatic colorectal cancer: a pooled analysis of TRIBE and TRIBE2 studies. Allegrini, G; Aprile, G; Bergamo, F; Boccaccino, A; Boni, L; Borelli, B; Buonadonna, A; Cordio, S; Cremolini, C; Dell'Aquila, E; Falcone, A; Latiano, TP; Libertini, M; Lonardi, S; Marmorino, F; Masi, G; Moretto, R; Passardi, A; Pella, N; Randon, G; Ratti, M; Ricci, V; Ronzoni, M; Rossini, D; Tamburini, E; Urbano, F; Zucchelli, G, 2019)	0.51
"Studies of patients treated with bevacizumab and other vascular epithelial growth factor (VEGF) inhibitors have reported that hypertension adverse events (AEs) are associated with improved overall survival (OS) or progression-free survival (PFS)."	( Effect of Early Adverse Events on Survival Outcomes of Patients with Metastatic Colorectal Cancer Treated with Ramucirumab. Hopkins, AM; Karapetis, CS; Lim, HH; Rowland, A; Sorich, MJ; Yuen, HY, 2019)	0.51
"1%) experienced ≥ 1 treatment-emergent adverse event (TEAE; grade ≥ 3; 34/54; 63."	( Antitumor Activity and Safety of Trastuzumab Deruxtecan in Patients With HER2-Low-Expressing Advanced Breast Cancer: Results From a Phase Ib Study. Doi, T; Fujisaki, Y; Iwata, H; Krop, IE; Lee, C; Modi, S; Moreno-Aspitia, A; Murthy, RK; Park, H; Redfern, C; Sagara, Y; Shahidi, J; Sugihara, M; Takahashi, S; Tamura, K; Tsurutani, J; Zhang, L, 2020)	0.56
" A modified FOLFOXIRI regimen is also widely used to reduce adverse events."	( Efficacy and Safety of Modified FOLFOXIRI+α in the Treatment of Advanced and Recurrent Colorectal Cancer: A Single-center Experience. Adachi, T; Eguchi, S; Enjoji, T; Hidaka, M; Inoue, Y; Ito, S; Kanetaka, K; Kobayashi, K; Kosaka, T; Kuba, S; Okada, S; Takatsuki, M; Tetsuo, H; Torashima, Y; Yamaguchi, S; Yamanouchi, K, 2020)	0.56
" There was no association between IVS14 + 1 G > A polymorphism and the occurrence of adverse reactions."	( Evaluation of adverse effects of chemotherapy regimens of 5-fluoropyrimidines derivatives and their association with DPYD polymorphisms in colorectal cancer patients. Abdhaghighi, MJ; Jalali, H; Janbabaei, G; Negarandeh, R; Nosrati, A; Saghafi, F; Salehifar, E, 2020)	0.56
"FOLFOX and FOLFIRI were the most common regimens in CRC patients and their toxicity profile was different in some adverse reactions."	( Evaluation of adverse effects of chemotherapy regimens of 5-fluoropyrimidines derivatives and their association with DPYD polymorphisms in colorectal cancer patients. Abdhaghighi, MJ; Jalali, H; Janbabaei, G; Negarandeh, R; Nosrati, A; Saghafi, F; Salehifar, E, 2020)	0.56
"3%) permanently discontinued treatment due to adverse events (AEs)."	( Sacituzumab govitecan, a Trop-2-directed antibody-drug conjugate, for patients with epithelial cancer: final safety and efficacy results from the phase I/II IMMU-132-01 basket trial. Bardia, A; Berlin, JD; Chang, JC; Goldenberg, DM; Goswami, T; Gray, JE; Hong, Q; Kalinsky, K; Kio, EA; Komiya, T; Lang, JM; Maliakal, P; Masters, GA; Messersmith, WA; Moroose, R; O'Shaughnessy, J; Ocean, AJ; Picozzi, V; Santin, AD; Sharkey, RM; Starodub, A; Vahdat, L; Wegener, WA, 2021)	0.62
" T-DXd treatment is associated with gastrointestinal and hematological adverse events, and a risk of interstitial lung disease (ILD), with the ILD risk being higher in Japan than in countries other than Japan."	( Discovery and development of trastuzumab deruxtecan and safety management for patients with HER2-positive gastric cancer. Baba, E; Fujii, S; Fujitani, K; Oki, E; Shitara, K; Yamaguchi, K, 2021)	0.62
" We evaluated the associations between the UGT1A1 genotype linked to adverse events-caused by irinotecan-and the efficacy and safety of mXELIRI and FOLFIRI."	( Impact of UGT1A1 genotype on the efficacy and safety of irinotecan-based chemotherapy in metastatic colorectal cancer. Ahn, JB; Bai, L; Cho, SH; Fang, WJ; Han, SW; Hong, YS; Iwasa, S; Kim, TW; Kotaka, M; Lee, KW; Matsuoka, H; Morita, S; Muro, K; Nakamura, M; Nishina, T; Park, YS; Sakamoto, J; Yamada, Y; Yuan, XL; Yuan, Y; Zhang, DS, 2021)	0.62
" However, safe and universal therapeutic platforms implementing such immune effects remain scarce."	( Immunogenic camptothesome nanovesicles comprising sphingomyelin-derived camptothecin bilayers for safe and synergistic cancer immunochemotherapy. Chen, J; Han, W; Lambesis, KT; Le, KT; Little, N; Lu, J; Scott, AJ; Wang, Z, 2021)	0.85
" Patients exhibiting EWL had worse survival and higher frequencies of adverse events."	( Early weight loss is an independent risk factor for shorter survival and increased side effects in patients with metastatic colorectal cancer undergoing first-line treatment within the randomized Phase III trial FIRE-3 (AIO KRK-0306). Algül, H; Decker, T; Erickson, NT; Gesenhues, AB; Heinemann, V; Heintges, T; Höffkes, HG; Holch, JW; Kahl, C; Kaiser, F; Kiani, A; Kullmann, F; Lerch, MM; Link, H; Liu, L; Michl, M; Modest, DP; Moehler, M; Ricard, I; Scheithauer, W; Stintzing, S; Theurich, S; von Weikersthal, LF, 2022)	0.72
" Grade ≥ 3 adverse events were more frequently observed in group O (90 vs."	( Comparison of safety and efficacy of fluorouracil + oxaliplatin + irinotecan (FOLFOXIRI) and modified FOLFOXIRI with bevacizumab for metastatic colorectal cancer: data from clinical practice. Aoyama, T; Kazama, K; Numata, M; Oshima, T; Rino, Y; Sato, M; Sato, S; Shiozawa, M; Sugano, N; Tamagawa, H; Uchiyama, M; Yukawa, N, 2022)	0.72
"Machine learning (ML) algorithms have been used to forecast clinical outcomes or drug adverse effects by analyzing different data sets such as electronic health records, diagnostic data, and molecular data."	( Machine Learning Application in a Phase I Clinical Trial Allows for the Identification of Clinical-Biomolecular Markers Significantly Associated With Toxicity. Bedon, L; Buonadonna, A; Cecchin, E; Dal Bo, M; Fabbiani, E; Polano, M; Toffoli, G, 2022)	0.72
"Aflibercept in combination with FOLFIRI chemotherapy is an established safe and efficacious regimen for the treatment of mCRC as second-line chemotherapy."	( Safety and efficacy review of aflibercept for the treatment of metastatic colorectal cancer. Chau, I; Lau, DK; Mencel, J, 2022)	0.72
" However, under human physiological conditions, the rapid opening of lactone ring of 9-NC resulting in the formation of inactive and high toxic carboxylate limited its clinical efficacy."	( 9-Nitro-20(S)-carbonate-camptothecin (NCP4), a novel prodrug of 9-nitrocamptothecin (9-NC), exhibits potent chemotherapeutic efficacy and improved safety against hepatocarcinoma. Chen, Y; Pan, J; Qing, C; Sun, Y; Tian, Y; Zhang, Y; Zhou, H; Zhu, Q, 2022)	1.03
" A total of 514 adverse events (AEs) occurred in 134 patients, of which 206 (49."	( Safety and effectiveness of aflibercept in combination with FOLFIRI in Korean patients with metastatic colorectal cancer who received oxaliplatin-containing regimen. Ahn, MS; Bae, BN; Baik, SH; Beom, SH; Han, SW; Jeon, SY; Jo, HJ; Kang, MH; Kim, DH; Kim, HK; Kim, JG; Kim, JH; Kim, JS; Kim, JY; Lee, MA; Lee, S; Oh, J; Park, I; Park, YS; Shin, SH; Yoon, JA; Zang, DY, 2023)	0.91
"Chemotherapy-related adverse events (AEs) can negatively impact the care of patients."	( Real-world safety and supportive care use of second-line 5-fluorouracil-based regimens among patients with metastatic pancreatic ductal adenocarcinoma. Cockrum, P; Kim, G; Surinach, A; Wainberg, Z; Wang, S, 2022)	0.72
"In patients with mPDAC who received second-line therapy, those who received liposomal irinotecan-based regimens had the lowest rates of anemia, neutropenia, and thrombocytopenia compared to FOLFIRI, FOLFIRINOX, and FOLFOX, while requiring a similar or lower level of medication to treat and manage those adverse events."	( Real-world safety and supportive care use of second-line 5-fluorouracil-based regimens among patients with metastatic pancreatic ductal adenocarcinoma. Cockrum, P; Kim, G; Surinach, A; Wainberg, Z; Wang, S, 2022)	0.72
" In addition to efficacy, successful implementation of any new anticancer therapy includes learning how to prevent, monitor, and manage treatment-related adverse events."	( Clinical Practices and Institutional Protocols on Prophylaxis, Monitoring, and Management of Selected Adverse Events Associated with Trastuzumab Deruxtecan. Armitage, M; Bardia, A; Harnden, K; Mauro, L; Pennisi, A; Soliman, H, 2022)	0.72
" The most frequent grade 3/4 adverse events were: asthenia (21."	( Efficacy and safety of FOLFIRI/aflibercept (FA) in an elderly population with metastatic colorectal cancer (mCRC) after failure of an oxaliplatin-based regimen. Alonso de Castro, B; Cameselle García, S; Carmona Campos, M; Cousillas Castiñeiras, A; De la Cámara Gómez, JC; Fernández-Montes, A; Gómez-Randulfe Rodríguez, MI; González Villarroel, P; Martínez-Lago, N; Méndez Méndez, JC; Romero Reinoso, C; Salgado Fernández, M; Vidal Insua, Y, 2022)	0.72
" Overall survival, progression-free survival, tumor response, and adverse events were evaluated."	( Long-term Survival, Tolerability, and Safety of First-Line Bevacizumab and FOLFIRI in Combination With Ginsenoside-Modified Nanostructured Lipid Carrier Containing Curcumin in Patients With Unresectable Metastatic Colorectal Cancer. Baek, JH; Jeon, Y; Sym, SJ; Yoo, BK, )	0.13
" The most common grade 3 or higher adverse events were neutropenia (n = 15, 34."	( Long-term Survival, Tolerability, and Safety of First-Line Bevacizumab and FOLFIRI in Combination With Ginsenoside-Modified Nanostructured Lipid Carrier Containing Curcumin in Patients With Unresectable Metastatic Colorectal Cancer. Baek, JH; Jeon, Y; Sym, SJ; Yoo, BK, )	0.13
" The association between the occurrence of severe adverse events, pharmacokinetics parameters, and UGT1A1 and CYP3A4 predicted phenotypes was evaluated, as the evaluation of [SN-38]/IRI dose ratio as predictor of severe adverse events."	( Evaluation of UGT1A1 and CYP3A Genotyping and Single-Point Irinotecan and Metabolite Concentrations as Predictors of the Occurrence of Adverse Events in Cancer Treatment. Antunes, MV; Basso, J; Hahn, RZ; Ibaldi, MR; Linden, R; Pavei, CC; Schaefer, VD; Schwartsmann, G, 2023)	0.91
" Data on adverse event was reported."	( Evaluation of UGT1A1 and CYP3A Genotyping and Single-Point Irinotecan and Metabolite Concentrations as Predictors of the Occurrence of Adverse Events in Cancer Treatment. Antunes, MV; Basso, J; Hahn, RZ; Ibaldi, MR; Linden, R; Pavei, CC; Schaefer, VD; Schwartsmann, G, 2023)	0.91
"5%) developed grade 3/4 adverse events."	( Evaluation of UGT1A1 and CYP3A Genotyping and Single-Point Irinotecan and Metabolite Concentrations as Predictors of the Occurrence of Adverse Events in Cancer Treatment. Antunes, MV; Basso, J; Hahn, RZ; Ibaldi, MR; Linden, R; Pavei, CC; Schaefer, VD; Schwartsmann, G, 2023)	0.91
" Treatment regimens, body surface area, dosage, number of treatment courses, and adverse events( AEs) were evaluated."	( [Comparative Safety Assessment of Ramucirumab plus FOLFIRI and Bevacizumab plus FOLFIRI in Second- and Later-Line Treatment in Japanese Patients with Metastatic Colorectal Carcinoma]. Iwai, M; Kimura, M; Usami, E; Yoshimura, T, 2022)	0.72
" The prognosis, predictive factors (including systemic inflammation-based prognostic indicators), and adverse events were investigated."	( Efficacy and Safety of the Combination of Nano-Liposomal Irinotecan and 5-Fluorouracil/L-Leucovorin in Unresectable Advanced Pancreatic Cancer: A Real-World Study. Aihara, R; Araki, K; Hatanaka, T; Hosaka, H; Hoshino, T; Hosouchi, Y; Ijima, M; Ishida, F; Ishii, N; Kakizaki, S; Kobatake, T; Kurihara, E; Naganuma, A; Shirabe, K; Suzuki, Y; Tamura, Y; Uraoka, T; Yasuoka, H; Yoshida, S, 2022)	0.72
" Adverse events were manageable, although gastrointestinal symptoms and neutropenia were observed."	( Efficacy and Safety of the Combination of Nano-Liposomal Irinotecan and 5-Fluorouracil/L-Leucovorin in Unresectable Advanced Pancreatic Cancer: A Real-World Study. Aihara, R; Araki, K; Hatanaka, T; Hosaka, H; Hoshino, T; Hosouchi, Y; Ijima, M; Ishida, F; Ishii, N; Kakizaki, S; Kobatake, T; Kurihara, E; Naganuma, A; Shirabe, K; Suzuki, Y; Tamura, Y; Uraoka, T; Yasuoka, H; Yoshida, S, 2022)	0.72
" The adverse events were also analyzed."	( Safety and efficacy of irinotecan, oxaliplatin, and capecitabine (XELOXIRI) regimen with or without targeted drugs in patients with metastatic colorectal cancer: a retrospective cohort study. Gao, L; Liu, X; Ma, X; Ou, K; Wang, Q; Yang, L; Zhang, H, 2022)	0.72
" The incidence of any grade of adverse events (AEs) was 96."	( Safety and efficacy of irinotecan, oxaliplatin, and capecitabine (XELOXIRI) regimen with or without targeted drugs in patients with metastatic colorectal cancer: a retrospective cohort study. Gao, L; Liu, X; Ma, X; Ou, K; Wang, Q; Yang, L; Zhang, H, 2022)	0.72
" There were no significant associations between genotypes and adverse drug reactions (ADRs) or ELT concentrations and ADRs."	( Relationship between CYP2C8, UGT1A1, and ABCG2 gene polymorphisms and the exposure, efficacy, and toxicity of eltrombopag in the treatment of refractory aplastic anemia. Chen, M; Han, B; Liu, B; Zhang, B; Zuo, W, 2022)	0.72
" Event rates were calculated for all adverse events (AEs) to evaluate the safety of DS-8201a."	( Safety and efficacy profile of Trastuzumab deruxtecan in solid cancer: pooled reanalysis based on clinical trials. Guo, W; Ma, X; Sun, J; Wang, Z; Xu, H; Zhang, H; Zhang, T; Zhong, X, 2022)	0.72
" Antibodies, cytotoxic drug, linker, and conjugation process are implicated in ADC profile, resulting in unique adverse drug reactions and toxicity heterogeneity within ADC class."	( [Chinese expert consensus of antibody-drug conjugate toxicity management for breast cancer]. , 2022)	0.72
" The criteria  for the inclusion of studies were previously defined based on the two secondary goals addressed in this review: 1) To analyze the magnitude of the differences  in clinical responses and 2) To study the magnitude of the differences in  adverse effects of irinotecan at high doses, as compared to the doses  described in the summary of product characteristics corresponding to the  FOLFIRI regimen in patients with metastatic colorectal cancer with genotypes  UGT1A1*1/* 1 or *1/*28."	( Efficacy and safety of high doses of irinotecan in patients with metastatic colorectal cancer treated with the FOLFIRI regimen based on the UGT1A1 genotype: A systematic review. García-Gil, S; Gutiérrez-Nicolás, F; Miarons, M; Riera, P, 2022)	0.72
" Most commonly, it is associated with coronary vasospasm secondary to direct toxic effects on vascular endothelium."	( Managing life-threatening 5-fluorouracil cardiotoxicity. Boldig, K; Ganguly, A; Kadakia, M; Rohatgi, A, 2022)	0.72
" However, severe adverse effects due to irinotecan have been observed even in patients who do not harbor UGT1A1*28 or *6."	( Association between a single nucleotide polymorphism in the R3HCC1 gene and irinotecan toxicity. Hamamoto, Y; Hazama, S; Iida, M; Ioka, T; Kanesada, K; Matsui, H; Nagano, H; Ogihara, H; Shindo, Y; Suzuki, N; Takeda, S; Tokumitsu, Y; Tsunedomi, R; Yoshida, S, 2023)	0.91
"We analyzed the incidence, time to first onset, and time to resolution for adverse events that require special attention and other selected toxicities in the nal-IRI combination group (n = 46)."	( Liposomal irinotecan with fluorouracil and leucovorin after gemcitabine-based therapy in Japanese patients with metastatic pancreatic cancer: additional safety analysis of a randomized phase 2 trial. Furuse, J; Furuya, M; Ikeda, M; Ioka, T; Okusaka, T; Teng, Z; Ueno, M, 2023)	0.91
"3%) were the most commonly reported treatment-emergent adverse events, with a median time to onset of 21."	( Liposomal irinotecan with fluorouracil and leucovorin after gemcitabine-based therapy in Japanese patients with metastatic pancreatic cancer: additional safety analysis of a randomized phase 2 trial. Furuse, J; Furuya, M; Ikeda, M; Ioka, T; Okusaka, T; Teng, Z; Ueno, M, 2023)	0.91
" Although the treatment-emergent adverse events occurred were controllable, patients with prolonged toxicities should be closely managed."	( Liposomal irinotecan with fluorouracil and leucovorin after gemcitabine-based therapy in Japanese patients with metastatic pancreatic cancer: additional safety analysis of a randomized phase 2 trial. Furuse, J; Furuya, M; Ikeda, M; Ioka, T; Okusaka, T; Teng, Z; Ueno, M, 2023)	0.91
" It was observed that there were fewer adverse events compared to the VELOUR trial."	( Efficacy and safety of folfiri plus aflibercept in second-line treatment of metastatic colorectal cancer: Real-life data from Turkish oncology group. Acar, R; Akbas, S; Akinci, MB; Araz, M; Arslan, C; Artac, M; Bahceci, A; Bilgetekin, I; Bilici, A; Cakir, E; Celik, E; Cilbir, E; Cincin, I; Dede, DS; Demirkiran, A; Deniz, GI; Dogan, I; Erdem, D; Erdogan, AP; Eren, OO; Erol, C; Garbioglu, DB; Gulmez, A; Hacibekiroglu, I; Hamdard, J; Hizal, M; Inal, A; Kahraman, S; Kaya, AO; Koca, S; Kubilay, P; Kucukarda, A; Kut, E; Mandel, NM; Menekse, S; Nayir, E; Oksuzoglu, B; On, S; Oyman, A; Ozyukseler, DT; Paydas, S; Sakin, A; Sen, E; Sendur Mehmet, AN; Sevinc, A; Taskaynatan, H; Tastekin, D; Turhal, S; Uncu, D; Yalcin, B; Yildirim, ME, 2022)	0.72
" Inhibition of gut microbial glucuronidase may also prevent adverse GI effects of CPT-11 in patients on opioids."	( Opioid-induced microbial dysbiosis disrupts irinotecan (CPT-11) metabolism and increases gastrointestinal toxicity in a murine model. Abu, YF; Chen, C; Meng, J; Ramakrishnan, S; Roy, S; Tao, J; Xie, Y; Yan, Y; Zhang, Y; Zhou, Y, 2023)	0.91
" The most common adverse reactions in grades 1-2 were decreased appetite (49."	( The efficacy and safety of trastuzumab deruxtecan (T-DXd) in HER2-expressing solid tumours: a single-arm meta-analysis. Chen, X; Kou, L; Li, J; Li, Y; Wen, Q; Xie, X, 2023)	0.91
" However, concerns remain about potentially serious treatment adverse events (e."	( The efficacy and safety of trastuzumab deruxtecan (T-DXd) in HER2-expressing solid tumours: a single-arm meta-analysis. Chen, X; Kou, L; Li, J; Li, Y; Wen, Q; Xie, X, 2023)	0.91
"Our meta-analysis shows that the aflibercept plus FOLFIRI combination shows better survival efficacies however; it is also associated with more high-grade adverse events."	( A systemic review and meta-analysis of Aflibercept plus FOLFIRI regimen as a second-line treatment for metastatic colorectal cancer: A PRISMA compliant pooled analysis of randomized controlled trials and single arm studies to assess efficacy and safety. Chorawala, MR; Patel, RS; Thakur, A, 2023)	0.91
"In clinical trials, the assessment of safety is traditionally focused on the overall rate of high-grade and serious adverse events (AEs)."	( Adverse events during first-line treatments for mCRC: The Toxicity over Time (ToxT) analysis of three randomised trials. Boccaccino, A; Bustreo, S; Carullo, M; Clavarezza, M; Cremolini, C; Cupini, S; Daniel, F; Libertini, M; Lonardi, S; Morano, F; Niger, M; Palermo, F; Pietrantonio, F; Procaccio, L; Raimondi, A; Rossini, D; Santini, D; Tomasello, G; Zaniboni, A, 2023)	0.91
" Outcome measures were any adverse events and survival."	( Efficacy and Safety of Trastuzumab Deruxtecan in Breast Cancer: A Systematic Review and Meta-Analysis. Boland, F; Daly, GR; Dowling, GP; Hennessy, BT; Hill, ADK; Keelan, S; Toomey, S, 2023)	0.91
" Number of cycles, dose delays for any cause, and dose reductions for adverse events (AEs) were comparable between age classes."	( Quality of life, effectiveness, and safety of aflibercept plus FOLFIRI in older patients with metastatic colorectal cancer: An analysis of the prospective QoLiTrap study. Anchisi, S; Bohanes, P; Derigs, HG; Geffriaud-Ricouard, C; Grünberger, B; Gueldner, M; Hofheinz, RD; Piringer, G; Scholten, F; Schwarz, L; Thaler, J; von Moos, R, 2023)	0.91

Pharmacokinetics

10-Hydroxy camptothecin (10-HCPT) is an antitumor agent effective in the treatment of several solid tumors. Its use is hampered by poor water solubility, low lactone stability, short plasma half-life. 10-H CPT-hydroxyethyl starch (HES) conjugates were prepared to improve the watersolubility and prolong the half- life in plasma.

Excerpt	Reference	Relevance
" A total of 64 pharmacokinetic sets (> or = 24-h sampling) were obtained in phase I studies at doses ranging from 50 to 750 mg/m2 (0."	( Limited sampling models for simultaneous estimation of the pharmacokinetics of irinotecan and its active metabolite SN-38. Chabot, GG, 1995)	0.29
" The plasma concentration-time curves were not compatible with standard linear pharmacokinetic models, and indications were found for the occurrence of nonlinear (saturation) kinetics at the dosages studied."	( Phase I clinical and pharmacokinetic study of topotecan administered by a 24-hour continuous infusion. Beijnen, JH; Davies, BE; Koier, I; Maes, RA; Rodenhuis, S; Rosing, H; ten Bokkel Huinink, WW; van Warmerdam, LJ, 1995)	0.29
"A linear two-compartment Bayesian pharmacokinetic model was developed using a standard two-stage population method for the novel anti-cancer agent CPT-11 from 11 adult patients with refractory cancer."	( Efficient sampling strategies for forecasting pharmacokinetic parameters of irinotecan (CPT-11): implication for area under the concentration-time curve monitoring. Arioka, H; Eguchi, K; Karato, A; Lieberman, R; Nakashima, H; Nomura, N; Ohmatsu, H; Shinkai, T; Shiraishi, J; Tamura, T, 1995)	0.29
" The relationship between pharmacokinetic parameters and pharmacodynamic effects was also investigated to elucidate the cause of interpatient variation in side effects."	( A pharmacokinetic and pharmacodynamic analysis of CPT-11 and its active metabolite SN-38. Eguchi, K; Hakusui, H; Miya, T; Mizuno, S; Morita, M; Ohe, Y; Saijo, N; Sasaki, Y; Shinkai, T; Tamura, T, 1995)	0.29
"The objective of this study was to develop a limited sampling model (LSM) to estimate the area under the curve (AUC) of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11) and that of 7-ethyl-10-hydroxycamptothecin (SN-38) as predictive pharmacokinetic variables for leukopenia and episodes of diarrhea induced by CPT-11 administration."	( A limited sampling model for estimating pharmacokinetics of CPT-11 and its metabolite SN-38. Fujii, H; Igarashi, T; Itoh, K; Miyata, Y; Mizuno, S; Ohtsu, T; Saijo, N; Sasaki, Y; Sekine, I; Wakita, H, 1995)	0.48
" During these trials the pharmacokinetics of CPT-11 and its active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38), were investigated to evaluate the relationship between pharmacokinetic parameters and diarrhea, since this is an unpredictable and severe toxicity of combination chemotherapy using CPT-11 and cisplatin."	( Relationship between the pharmacokinetics of irinotecan and diarrhea during combination chemotherapy with cisplatin. Fukuoka, M; Hirashima, T; Kudoh, S; Kusunoki, Y; Masuda, N; Matsui, K; Nakagawa, K; Negoro, S; Takifuji, N; Yoshikawa, A, 1995)	0.51
"We conducted a phase I and pharmacokinetic study to determine the maximum tolerable dose (MTD), toxicities, pharmacokinetic profile, and antitumor activity of Irinotecan (CPT-11) in patients with refractory solid malignancies."	( Phase I and pharmacokinetic study of irinotecan (CPT-11) administered daily for three consecutive days every three weeks in patients with advanced solid tumors. Catimel, G; Chabot, GG; Clavel, M; Cote, C; Dumortier, A; Engel, C; Gouyette, A; Guastalla, JP; Mahjoubi, M; Mathieu-Boué, A, 1995)	0.29
" Pharmacokinetic parameters were determined using model-independent and model-dependent analyses."	( Population pharmacokinetics and pharmacodynamics of irinotecan (CPT-11) and active metabolite SN-38 during phase I trials. Abigerges, D; Armand, JP; Bugat, R; Catimel, G; Chabot, GG; Culine, S; de Forni, M; Extra, JM; Hérait, P; Mahjoubi, M, 1995)	0.29
"168 pharmacokinetic data sets were obtained in 107 patients (97 first courses, 43 second courses, 23 third courses, 4 fourth courses, and 1 fifth course)."	( Population pharmacokinetics and pharmacodynamics of irinotecan (CPT-11) and active metabolite SN-38 during phase I trials. Abigerges, D; Armand, JP; Bugat, R; Catimel, G; Chabot, GG; Culine, S; de Forni, M; Extra, JM; Hérait, P; Mahjoubi, M, 1995)	0.29
" We performed a pharmacokinetic study as part of a phase I study in patients with various types of solid tumors, where topotecan was administered in a 30-min infusion daily on 5 consecutive days every 3 weeks."	( Pharmacokinetics and pharmacodynamics of topotecan administered daily for 5 days every 3 weeks. Beijnen, JH; Davies, BE; de Boer-Dennert, M; Maes, RA; Rosing, H; Schellens, JH; van Warmerdam, LJ; Verweij, J, 1995)	0.29
"To determine the feasibility of escalating the hydrophilic topoisomerase I (topo I)-inhibitor topotecan (TPT) above myelosuppressive doses in adults with refractory or relapsed acute leukemias and to assess pharmacodynamic determinants of TPT action."	( Phase I and pharmacodynamic study of the topoisomerase I-inhibitor topotecan in patients with refractory acute leukemia. Adjei, A; Burke, PJ; Cheng, YC; Donehower, RC; Gore, SD; Grochow, LB; Jones, RJ; Kaufmann, SH; Rowinsky, EK, 1994)	0.29
"In this study, we aimed to develop a population pharmacokinetic model for CPT-11 and to use the Bayesian method to estimate CPT-11 pharmacokinetic parameters in each of 43 patients who received combined therapy consisting of CPT-11 and etoposide."	( CPT-11: population pharmacokinetic model and estimation of pharmacokinetics using the Bayesian method in patients with lung cancer. Arioka, H; Eguchi, K; Karato, A; Nakashima, H; Ohe, Y; Oshita, F; Shinkai, T; Tamura, T; Uenaka, K; Yamamoto, N, 1994)	0.29
" Early human studies showed that topotecan (the active lactone) had a short half-life in plasma."	( Phase I/pharmacokinetic study of topotecan by 24-hour continuous infusion weekly. Brennan, JM; Haas, NB; Hudes, GR; LaCreta, FP; O'Dwyer, PJ; Ozols, RF; Walczak, J, 1994)	0.29
" In all cases, considerable effort has gone into detailed pharmacokinetic studies conducted before and during the clinical phase I studies."	( Pharmacokinetics and early clinical studies of selected new drugs. Cassidy, J; Graham, MA; Jodrell, D; Kaye, SB; Workman, P, 1993)	0.29
"The models were developed and validated using 34 pharmacokinetic curves in 19 patients who participated in a phase I study."	( Limited sampling models for topotecan pharmacokinetics. Beijnen, JH; Maes, RA; Rosing, H; Schellens, JH; van Warmerdam, LJ; Verweij, J, 1994)	0.29
" Half-life values could not be predicted with acceptable precision and accuracy."	( Limited sampling models for topotecan pharmacokinetics. Beijnen, JH; Maes, RA; Rosing, H; Schellens, JH; van Warmerdam, LJ; Verweij, J, 1994)	0.29
"We conducted a phase I and pharmacokinetic trial of CPT-11 (irinotecan) to characterize the maximum-tolerated dose (MTD), toxicities, pharmacokinetic profile, and antitumor effects in patients with refractory solid malignancies."	( Phase I and pharmacokinetic trial of weekly CPT-11. Burris, HA; Eckardt, JR; Hilsenbeck, SG; Kuhn, JG; Nelson, J; Rodriguez, GI; Rothenberg, ML; Smith, LS; Tristan-Morales, M; Weiss, GR, 1993)	0.29
" In the present investigation, the pharmacokinetic behavior of CA, its sodium salt CA, AC, and MC in mice was characterized using specific liquid chromatographic assays which permitted determination of the intact lactone and opened ring carboxylate forms of these compounds."	( Pharmacokinetics of the 9-amino and 10,11-methylenedioxy derivatives of camptothecin in mice. Malspeis, L; Supko, JG, 1993)	0.52
" This study was undertaken to better define the pharmacokinetic behavior of this highly unstable compound in both plasma and cerebrospinal fluid (CSF) and to measure the degree of CSF penetration of this novel antineoplastic agent."	( Plasma and cerebrospinal fluid pharmacokinetic study of topotecan in nonhuman primates. Balis, FM; Blaney, SM; Cole, DE; Godwin, K; Poplack, DG, 1993)	0.29
" A phase I and pharmacokinetic study was performed to determine the maximum tolerated dose (MTD) and dose-limiting toxicities, the incidence and severity of other toxicities, and the pharmacokinetics of topotecan in children."	( Pediatric phase I trial and pharmacokinetic study of topotecan administered as a 24-hour continuous infusion. Ames, MM; Balis, FM; Blaney, SM; Cole, DE; Craig, C; Hammond, D; Krailo, M; Poplack, DG; Reaman, G; Reid, JM, 1993)	0.29
"The purpose of this study was to describe the cerebrospinal fluid (CSF) penetration of topotecan in humans, to generate a pharmacokinetic model to simultaneously describe topotecan lactone and total concentrations in the plasma and CSF, and to characterize the CSF and plasma pharmacokinetics of topotecan administered as a continuous infusion (CI)."	( Cerebrospinal fluid pharmacokinetics and penetration of continuous infusion topotecan in children with central nervous system tumors. Baker, SD; Crom, WR; Gajjar, A; Heideman, RL; Kuttesch, JF; Stewart, CF, 1996)	0.29
" To clarify the pharmacokinetic difference between CPT-11 and SN-38, the plasma levels, tissue distribution and excretion of SN-38 were investigated after dosing rats with 14C-labeled SN-38."	( Pharmacokinetics of SN-38 [(+)-(4S)-4,11-diethyl-4,9-dihydroxy-1H- pyrano[3',4':6,7]-indolizino[1,2-b]quinoline-3,14(4H,12H)-dione], an active metabolite of irinotecan, after a single intravenous dosing of 14C-SN-38 to rats. Atsumi, R; Hakusui, H; Okazaki, O, 1995)	0.29
" However, despite the large interpatient pharmacokinetic variability, the importance of regular drug monitoring on this schedule can be questioned, as the pharmacodynamic variability was relatively small."	( Pharmacokinetics and pharmacodynamics of topotecan given on a daily-times-five schedule in phase II clinical trials using a limited-sampling procedure. Beijnen, JH; Creemers, GJ; Davies, BE; de Boer-Dennert, M; Maes, RA; Rodenhuis, S; Rosing, H; Schellens, JH; ten Bokkel Huinink, WW; van Warmerdam, LJ; Verweij, J, 1996)	0.29
"To construct limited-sampling models (LSMs) for irinotecan (CPT-11) pharmacokinetic (PK) measures."	( Limited-sampling models for irinotecan pharmacokinetics-pharmacodynamics: prediction of biliary index and intestinal toxicity. Gupta, E; Mick, R; Ratain, MJ; Vokes, EE, 1996)	0.29
" The mean total body clearance of the lactone form is 30 L/h/m2, with a mean elimination half-life (t1/2 beta) of 3 hours; renal clearance accounts for approximately 40% of the administered dose with a large interindividual variability."	( Clinical pharmacokinetics of topotecan. Beijnen, JH; Herben, VM; ten Bokkel Huinink, WW, 1996)	0.29
"A pharmacokinetic study was performed during a phase II clinical trial of irinotecan (CPT-11) to confirm the pharmacokinetic profile of this drug and its metabolite and to investigate interpatient and intrapatient pharmacokinetic variations and pharmacokinetic-pharmacodynamic relationships."	( Pharmacokinetics and pharmacodynamics of irinotecan during a phase II clinical trial in colorectal cancer. Pharmacology and Molecular Mechanisms Group of the European Organization for Research and Treatment of Cancer. Adenis, A; Brunet, R; Bugat, R; Canal, P; Dezeuze, A; Douillard, JY; Gay, C; Herait, P; Lokiec, F; Mathieu-Boue, A, 1996)	0.29
" No relationship was identified between any pharmacokinetic parameter and delayed diarrhea or therapeutic outcome."	( Pharmacokinetics and pharmacodynamics of irinotecan during a phase II clinical trial in colorectal cancer. Pharmacology and Molecular Mechanisms Group of the European Organization for Research and Treatment of Cancer. Adenis, A; Brunet, R; Bugat, R; Canal, P; Dezeuze, A; Douillard, JY; Gay, C; Herait, P; Lokiec, F; Mathieu-Boue, A, 1996)	0.29
" The relationship between neutropenia and both CPT-11 and SN-38 pharmacokinetic parameters confirms the results of previous studies."	( Pharmacokinetics and pharmacodynamics of irinotecan during a phase II clinical trial in colorectal cancer. Pharmacology and Molecular Mechanisms Group of the European Organization for Research and Treatment of Cancer. Adenis, A; Brunet, R; Bugat, R; Canal, P; Dezeuze, A; Douillard, JY; Gay, C; Herait, P; Lokiec, F; Mathieu-Boue, A, 1996)	0.29
" Pharmacokinetic studies were performed during the first infusion course."	( Phase I trial and pharmacokinetic (PK) and pharmacodynamics (PD) study of topotecan using a five-day course in children with refractory solid tumors: a pediatric oncology group study. Bell, B; Dryer, ZA; Grier, H; Kurtzberg, J; Pratt, CB; Santana, VM; Stewart, CF; Tubergen, DG; Vietti, TJ; Winick, N; Zamboni, WC, 1996)	0.29
" Using a limited sampling model, pharmacokinetic studies were performed in 36 of the 40 patients."	( Phase I trial and pharmacokinetic (PK) and pharmacodynamics (PD) study of topotecan using a five-day course in children with refractory solid tumors: a pediatric oncology group study. Bell, B; Dryer, ZA; Grier, H; Kurtzberg, J; Pratt, CB; Santana, VM; Stewart, CF; Tubergen, DG; Vietti, TJ; Winick, N; Zamboni, WC, 1996)	0.29
" On day 1 of treatment, CPT-11 alone was given by 90-minute infusion, and pharmacokinetic sampling was performed over 24 hours."	( Phase I clinical and pharmacokinetic study of irinotecan, fluorouracil, and leucovorin in patients with advanced solid tumors. Berkery, R; Dietz, A; Eng, M; Kanowitz, J; Kelsen, DP; Kemeny, NE; Locker, P; Saltz, LB; Schaaf, L; Spriggs, D; Staton, BA; Steger, C, 1996)	0.29
" Fifteen patients underwent extended pharmacokinetic sampling to determine the distribution and elimination kinetics of 9-AC."	( Pharmacodynamics and pharmacokinetics of a 72-hour infusion of 9-aminocamptothecin in adult cancer patients. Allegra, CJ; Arbuck, SG; Band, RA; Cantilena, LR; Chen, AP; Dahut, W; Grem, JL; Hamilton, JM; Harold, N; Liang, MD; Lieberman, R; Marino, MT; Nakashima, H; Takimoto, CH, 1997)	0.53
"We conducted a pharmacokinetic and pharmacodynamic evaluation of irinotecan (CPT-11) and determined the effect of race and sex on disposition and toxicity of CPT-11."	( Pharmacokinetic and pharmacodynamic evaluation of the topoisomerase inhibitor irinotecan in cancer patients. Gupta, E; Lestingi, TM; Mick, R; Ramirez, J; Ratain, MJ; Vokes, EE; Wang, X, 1997)	0.3
" Plasma concentrations can be described using a 2- or 3-compartment model with a mean terminal half-life ranging from 5 to 27 hours."	( Clinical pharmacokinetics of irinotecan. Chabot, GG, 1997)	0.3
" The in vitro pharmacokinetic determination of lactone levels of esters 6a and 7b showed that the biological life span of their lactone forms in human and mouse plasma significantly increased when compared with their mother compounds, camptothecin (3) and 9-nitrocamptothecin (4)."	( Alkyl esters of camptothecin and 9-nitrocamptothecin: synthesis, in vitro pharmacokinetics, toxicity, and antitumor activity. Cao, Z; Giovanella, B; Harris, N; Kozielski, A; Stehlin, JS; Vardeman, D, 1998)	0.83
"To examine the pharmacokinetic relationships between humans and monkeys, we studied the disposition of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11) and its active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38), in rhesus monkeys."	( Pharmacokinetics of CPT-11 in rhesus monkeys. Hakusui, H; Inaba, M; Ishii, H; Ito, K; Mizuno, N; Ohnishi, Y; Sudoh, K; Sugiyama, Y; Tanioka, Y; Yoshida, Y, 1998)	0.5
"CPT-11 was administered to a total of six monkeys at doses of 3, 7, 15 and 25 mg/kg by intravenous infusion for 10 min and plasma concentrations and pharmacokinetic parameters of CPT-11 determined."	( Pharmacokinetics of CPT-11 in rhesus monkeys. Hakusui, H; Inaba, M; Ishii, H; Ito, K; Mizuno, N; Ohnishi, Y; Sudoh, K; Sugiyama, Y; Tanioka, Y; Yoshida, Y, 1998)	0.3
" Mean values of systemic clearance, mean residence time and distribution volume at steady state, the major pharmacokinetic parameters for CPT-11, were 13."	( Pharmacokinetics of CPT-11 in rhesus monkeys. Hakusui, H; Inaba, M; Ishii, H; Ito, K; Mizuno, N; Ohnishi, Y; Sudoh, K; Sugiyama, Y; Tanioka, Y; Yoshida, Y, 1998)	0.3
" Pharmacokinetic analysis of total 9-AC showed highly variable apparent oral 9-AC clearance and half-life."	( Phase I clinical and pharmacokinetic study of oral 9-aminocamptothecin (NSC-603071). Fleming, GF; Iyer, L; Janisch, L; Mani, S; Ratain, MJ; Schilsky, RL; Wang, X, 1998)	0.54
" The proposed method has been implemented in a phase I clinical trial for pharmacokinetic evaluation of this potential new drug."	( High-performance liquid chromatographic analysis of the investigational anticancer drug 9-aminocamptothecin, as the lactone form and as the total of the lactone and the hydroxycarboxylate forms, in micro-volumes of human plasma. Beijnen, JH; Bult, A; Herben, VM; Hillebrand, MJ; ten Bokkel Huinink, WW; van Gijn, R, 1998)	0.52
" The plasma pharmacokinetics of SPI-355 in rats were typical of those of other pegylated liposomal formulations, with significantly increased blood circulation time; the dose-corrected area under the curve and Cmax of SPI-355 (10 mg/kg) were 1250- and 35-fold higher, respectively, than those of nonliposomal GL14711C (8."	( Encapsulation of the topoisomerase I inhibitor GL147211C in pegylated (STEALTH) liposomes: pharmacokinetics and antitumor activity in HT29 colon tumor xenografts. Amantea, M; Colbern, GT; Dykes, DJ; Engbers, C; Hiller, A; Luzzio, M; Musterer, R; Pegg, E; Saville, R; Uster, P; Weng, S; Working, PK, 1998)	0.3
"The clinical pharmacokinetics of irinotecan (CPT11) can be described by a 2 or 3 compartment model, a mean terminal half-life of 12 hours, a volume of distribution at steady state of 168 l/m2 and a total body clearance of 15 l/m2/h."	( [Irinotecan pharmacokinetics]. Canal, P; Chabot, GG; Lokiec, F; Robert, J, 1998)	0.3
"We conducted a phase I dose-escalation trial of orally administered irinotecan (CPT-11) to characterize the maximum-tolerated dose (MTD), dose-limiting toxicities (DLTs), pharmacokinetic profile, and antitumor effects in patients with refractory malignancies."	( Phase I and pharmacokinetic trial of oral irinotecan administered daily for 5 days every 3 weeks in patients with solid tumors. Drengler, RL; Elfring, GL; Hammond, LA; Hodges, S; Kraynak, MA; Kuhn, JG; Locker, PK; Miller, LL; Rodriguez, GI; Rothenberg, ML; Schaaf, LJ; Staton, BA; Stephenson, JA; Villalona-Calero, MA; Von Hoff, DD, 1999)	0.3
" The biologic activity and favorable pharmacokinetic characteristics make oral administration of CPT-11 an attractive option for further clinical development."	( Phase I and pharmacokinetic trial of oral irinotecan administered daily for 5 days every 3 weeks in patients with solid tumors. Drengler, RL; Elfring, GL; Hammond, LA; Hodges, S; Kraynak, MA; Kuhn, JG; Locker, PK; Miller, LL; Rodriguez, GI; Rothenberg, ML; Schaaf, LJ; Staton, BA; Stephenson, JA; Villalona-Calero, MA; Von Hoff, DD, 1999)	0.3
"Our data indicate that the large interindividual pharmacodynamic variability in response to 9-aminocamptothecin is caused mainly by a variability in kinetic characteristics, suggesting that a kinetic-dynamic guided study design is warranted in future clinical investigations."	( Clinical pharmacokinetics of encapsulated oral 9-aminocamptothecin in plasma and saliva. Dallaire, BK; de Jonge, MJ; Loos, WJ; Sparreboom, A; Verweij, J, 1999)	0.77
" Pharmacokinetics permits the prediction of the occurrence of iatrogenic toxicities taking into account the interpatient variability of the pharmacokinetic parameters."	( [Usefulness of a pharmacokinetic approach for clinical antineoplastic chemotherapy evaluation]. Lokiec, F, 1999)	0.3
"The purpose of this study was to assess the efficacy and toxicity of a combination of cisplatin and irinotecan (CPT-11) in the treatment of patients with malignant pleural mesothelioma and to characterize the pharmacokinetic profiles of CPT-11 and its active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38)."	( Cisplatin in combination with irinotecan in the treatment of patients with malignant pleural mesothelioma: a pilot phase II clinical trial and pharmacokinetic profile. Chahinian, AP; Higashino, K; Miyake, M; Nakano, T; Ninomiya, K; Shinjo, M; Togawa, N; Tonomura, A; Yamamoto, T, 1999)	0.48
" To investigate a pharmacokinetic interaction between 9-AC and anticonvulsants, and to evaluate the pharmacodynamics of 9-AC, we investigated the clinical pharmacology of 9-AC, administered by a 72-h infusion, in three Phase II studies."	( Pharmacokinetics and pharmacodynamics of 9-aminocamptothecin infused over 72 hours in phase II studies. Lad, TE; Minami, H; Nicholas, MK; Ratain, MJ; Vokes, EE, 1999)	0.56
" These data indicate that the toxicity of the combination CPT-11 and CDDP is schedule independent and that there is no mutual pharmacokinetic interaction."	( Drug-administration sequence does not change pharmacodynamics and kinetics of irinotecan and cisplatin. Brouwer, E; de Boer-Dennert, MM; de Bruijn, P; de Jonge, MJ; Planting, AS; Sparreboom, A; Stoter, G; van der Burg, ME; Vernillet, L; Verweij, J, 1999)	0.3
" No plasmatic pharmacokinetic interactions were detected."	( Combination of oxaliplatin plus irinotecan in patients with gastrointestinal tumors: results of two independent phase I studies with pharmacokinetics. Besmaine, A; Cuvier, C; Cvitkovic, E; Dupont-André, G; Goldwasser, F; Kalla, S; Lokiec, F; Mahjoubi, M; Marty, M; Méry-Mignard, D; Misset, JL; Ouldkaci, M; Wasserman, E, 1999)	0.3
" Pharmacokinetic measurements were performed on days 1 and 5 of the first cycle and on day 4 of subsequent cycles using high-performance liquid chromatography."	( Phase I and pharmacokinetic study of a daily times 5 short intravenous infusion schedule of 9-aminocamptothecin in a colloidal dispersion formulation in patients with advanced solid tumors. Beijnen, JH; Herben, VM; Hillebrand, MJ; Lieverst, J; Porro, MG; Schellens, JH; Schoemaker, NE; Schot, M; ten Bokkel Huinink, WW; van Gijn, R, 1999)	0.52
" For pharmacokinetic analysis, serial plasma samples were obtained on days 1 through 3 of the first cycle."	( Pharmacokinetic, metabolic, and pharmacodynamic profiles in a dose-escalating study of irinotecan and cisplatin. Brouwer, E; de Boer-Dennert, MM; de Bruijn, P; de Jonge, MJ; Jacques, C; Mathijssen, RH; Sparreboom, A; van Alphen, RJ; Vernillet, L; Verweij, J, 2000)	0.31
"Irinotecan and cisplatin demonstrated linear pharmacokinetics comparable to that observed with single-agent administration, which suggests an absence of pharmacokinetic interaction."	( Pharmacokinetic, metabolic, and pharmacodynamic profiles in a dose-escalating study of irinotecan and cisplatin. Brouwer, E; de Boer-Dennert, MM; de Bruijn, P; de Jonge, MJ; Jacques, C; Mathijssen, RH; Sparreboom, A; van Alphen, RJ; Vernillet, L; Verweij, J, 2000)	0.31
"There was no apparent pharmacokinetic interaction between irinotecan and cisplatin in this study."	( Pharmacokinetic, metabolic, and pharmacodynamic profiles in a dose-escalating study of irinotecan and cisplatin. Brouwer, E; de Boer-Dennert, MM; de Bruijn, P; de Jonge, MJ; Jacques, C; Mathijssen, RH; Sparreboom, A; van Alphen, RJ; Vernillet, L; Verweij, J, 2000)	0.31
" Pharmacokinetic analyses were performed to evaluate the effect of irinotecan on the disposition of docetaxel."	( Phase I and pharmacokinetic study of irinotecan and docetaxel in patients with advanced solid tumors: preliminary evidence of clinical activity. Adjei, AA; Alberts, SR; Atherton, P; Erlichman, C; Goldberg, RM; Hanson, LJ; Kastrissios, H; Klein, CE; Pitot, HC; Reid, JM; Rubin, J; Sloan, JA, 2000)	0.31
" Pharmacokinetic parameters were calculated from the corrected data for dialysate concentrations of camptothecin versus time."	( Measurement and pharmacokinetics of unbound 20(S)-camptothecin in rat blood and brain by microdialysis coupled to microbore liquid chromatography with fluorescence detection. Chen, CF; Chen, YF; Chou, CJ; Tsai, TH, 2000)	0.78
" When judging from apparent simple pharmacokinetic analysis, an inconsistency was found between the in vitro drug release and the plasma level to a fair extent, but overall the in vivo drug release rate from microspheres was considered parallel to the in vitro one."	( Pharmacokinetics of prolonged-release CPT-11-loaded microspheres in rats. Hata, H; Kurita, A; Machida, Y; Morikawa, A; Onishi, H, 2000)	0.31
" Plasma decay is biphasic with a terminal half-life of 11."	( Simple and rapid determination of irinotecan and its metabolite SN-38 in plasma by high-performance liquid-chromatography: application to clinical pharmacokinetic studies. Aldaz, A; Calvo, E; Castellanos, C; Escoriaza, J; Giráldez, J, 2000)	0.31
"A Phase I study was performed to determine the maximum tolerated dose (MTD), toxicities, and pharmacokinetic profile of irinotecan (CPT-11) and its active metabolites when given on a once-every-3-week schedule."	( Phase I dose-finding and pharmacokinetic trial of irinotecan hydrochloride (CPT-11) using a once-every-three-week dosing schedule for patients with advanced solid tumor malignancy. Adjei, AA; Alberts, SA; Burch, PA; Elfring, G; Erlichman, C; Goldberg, RM; Miller, LL; Pitot, HC; Reid, JM; Rubin, J; Schaaf, LJ; Skaff, PA; Sloan, JA, 2000)	0.31
" The sequence of drug administration produced no significant differences in the pharmacokinetic parameters of irinotecan or SN-38, which were similar to the values reported when irinotecan is administered alone."	( Dose escalation and pharmacokinetic study of irinotecan in combination with paclitaxel in patients with advanced cancer. Burtness, BA; Cheng, Y; DiStasio, SA; Leffert, JJ; Li, X; McKeon, A; Murren, JR; Peccerillo, K; Pizzorno, G, 2000)	0.31
"To assess the feasibility of administering DX-8951f (exatecan mesylate), a water-soluble, camptothecin analog, as a 30-minute intravenous infusion daily for 5 days every 3 weeks, determine the maximum-tolerated dose (MTD) and pharmacokinetic (PK) behavior of DX-8951f, and seek preliminary evidence of anticancer activity."	( DX-8951f, a hexacyclic camptothecin analog, on a daily-times-five schedule: a phase I and pharmacokinetic study in patients with advanced solid malignancies. Coyle, J; De Jager, RL; Drengler, R; Eckhardt, SG; Geyer, CE; Hammond, LA; Johnson, TR; Rizzo, J; Rowinsky, EK; Schwartz, G; Smetzer, L; Tolcher, A; Von Hoff, DD, 2000)	0.84
"We conducted a phase I and pharmacokinetic study of docetaxel in combination with irinotecan to determine the dose-limiting toxicity (DLT), the maximum-tolerated dose (MTD), and the dose at which at least 50% of the patients experienced a DLT during the first cycle, and to evaluate the safety and pharmacokinetic profiles in patients with advanced solid tumors."	( Phase I and pharmacokinetic study of docetaxel and irinotecan in patients with advanced solid tumors. Armand, JP; Bruno, R; Couteau, C; Ducreux, M; Lebecq, A; Lefresne-Soulas, F; Lokiec, F; Risse, ML; Riva, A; Rougier, P; Ruffié, P, 2000)	0.31
"To determine the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetic (PK) profile, and recommended phase II dose of Exatecan mesylate (DX-8951f) when administered as a 24-hour continuous infusion every 3 weeks to patients with solid tumors."	( Phase I and pharmacokinetic study of exatecan mesylate (DX-8951f): a novel camptothecin analog. Coyle, J; De Jager, R; Ducharme, MP; Dumas, P; Hoff, PM; Lassere, Y; Lee, JJ; Pazdur, R; Royce, ME, 2001)	0.54
" The plasma clearance, total volume of distribution, and terminal elimination half-life were approximately 3 L/h, 40 L, and 14 hours, respectively."	( Phase I and pharmacokinetic study of exatecan mesylate (DX-8951f): a novel camptothecin analog. Coyle, J; De Jager, R; Ducharme, MP; Dumas, P; Hoff, PM; Lassere, Y; Lee, JJ; Pazdur, R; Royce, ME, 2001)	0.54
"4 is an appropriate drug carrier for T-0128 regarding plasma half-life and passive tumor targeting."	( Carrier and dose effects on the pharmacokinetics of T-0128, a camptothecin analogue-carboxymethyl dextran conjugate, in non-tumor- and tumor-bearing rats. Harada, M; Murata, J; Okuno, S; Sakakibara, H; Sakamura, Y; Suzuki, T, 2001)	0.55
" That of Cmax of CPT-11 included sex and BMI (F=8."	( Factors affecting the pharmacokinetics of CPT-11: the body mass index, age and sex are independent predictors of pharmacokinetic parameters of CPT-11. Fujii, H; Goya, T; Igarashi, T; Itoh, K; Minami, H; Miya, T; Ohtsu, T; Sasaki, Y, 2001)	0.31
"Individual plasma-converting enzyme activity was measured in 20 adult cancer patients participating in a pharmacokinetic and phase I clinical trial of a prolonged 96-h intravenous infusion of irinotecan."	( Human plasma carboxylesterase and butyrylcholinesterase enzyme activity: correlations with SN-38 pharmacokinetics during a prolonged infusion of irinotecan. Band, R; Bowen, D; Cottrell, J; Grem, JL; Guemei, AA; Hehman, H; Ismail, AS; Pavlov, MV; Prudhomme, M; Takimoto, CH; Taylor, RE, 2001)	0.31
" Pharmacokinetic variations in the relative exposure to SN-38 did not correlate with the measured carboxylesterase-converting enzyme activity nor with plasma butyrylcholinesterase activity in our patient population."	( Human plasma carboxylesterase and butyrylcholinesterase enzyme activity: correlations with SN-38 pharmacokinetics during a prolonged infusion of irinotecan. Band, R; Bowen, D; Cottrell, J; Grem, JL; Guemei, AA; Hehman, H; Ismail, AS; Pavlov, MV; Prudhomme, M; Takimoto, CH; Taylor, RE, 2001)	0.31
" Pharmacokinetic analysis of irinotecan and its metabolites was performed after each cycle."	( Sequence effect of irinotecan and fluorouracil treatment on pharmacokinetics and toxicity in chemotherapy-naive metastatic colorectal cancer patients. Allegrini, G; Comis, S; Conte, P; Danesi, R; Del Tacca, M; Di Paolo, A; Falcone, A; Lencioni, M; Masi, G; Pfanner, E, 2001)	0.31
" Pharmacokinetic analysis revealed that the administration sequence significantly affected the SN-38 area under the concentration-versus-time curve (AUC), which was 40."	( Sequence effect of irinotecan and fluorouracil treatment on pharmacokinetics and toxicity in chemotherapy-naive metastatic colorectal cancer patients. Allegrini, G; Comis, S; Conte, P; Danesi, R; Del Tacca, M; Di Paolo, A; Falcone, A; Lencioni, M; Masi, G; Pfanner, E, 2001)	0.31
" Pharmacokinetic parameters of camptothecin were assessed using a non-compartmental model."	( Effect of P-glycoprotein modulators on the pharmacokinetics of camptothecin using microdialysis. Lee, CH; Tsai, TH; Yeh, PH, 2001)	0.84
" Several pharmacokinetic and pharmacodynamic factors including cellular efflux, modulation of topoisomerases I and II, lactone stability, alterations in metabolism, and drug-drug interactions, influence the antitumor response and toxicity of these agents."	( Cellular, pharmacokinetic, and pharmacodynamic aspects of response to camptothecins: can we improve it? Jung, LL; Zamboni, WC, 2001)	0.54
" As a surrogate for the UGT activity, the polymorphic frequency distribution of the area under the concentration-time curve (AUC) ratios of SN-38 to SN-38G (AUC(SN-38)/AUC(SN-38G)) using pooled pharmacokinetic data from four independent study groups in Japan was explored."	( Polymorphisms of UDP-glucuronosyltransferase and pharmacokinetics of irinotecan. Ando, Y; Hasegawa, Y; Ichiki, M; Shimokata, K; Sugiyama, T; Ueoka, H, 2002)	0.31
"This trial was performed to determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and pharmacokinetic profile of irinotecan (CPT-11) when administered on a once-every-2-week schedule."	( Phase I dose-finding and pharmacokinetic trial of irinotecan (CPT-11) administered every two weeks. Eckhardt, SG; Elfring, GL; Hammond, LA; Hodges, S; Kuhn, JG; Locker, PK; Miller, LL; Petit, RG; Rinaldi, DA; Rodriguez, GI; Rothenberg, ML; Schaaf, LJ; Sharma, A; Villalona-Calero, MA; von Hoff, DD, 2001)	0.31
" No predictive correlation was observed between CPT-11 or SN-38 peak concentration or AUC and first-cycle diarrhea, neutropenia, nausea, or vomiting."	( Phase I dose-finding and pharmacokinetic trial of irinotecan (CPT-11) administered every two weeks. Eckhardt, SG; Elfring, GL; Hammond, LA; Hodges, S; Kuhn, JG; Locker, PK; Miller, LL; Petit, RG; Rinaldi, DA; Rodriguez, GI; Rothenberg, ML; Schaaf, LJ; Sharma, A; Villalona-Calero, MA; von Hoff, DD, 2001)	0.31
" We performed a Phase I and pharmacokinetic study to investigate CPT-11 by hepatic arterial administration in patients with liver metastases."	( Continuous administration of irinotecan by hepatic arterial infusion: a phase I and pharmacokinetic study. Gall, H; Giaccone, G; Gruia, G; Kedde, MA; Leisink, JM; Pinedo, HM; van der Vijgh, WJ; van Groeningen, CJ; van Riel, JM, 2002)	0.31
"We performed PMC-CPT-11 therapy (modified pharmacokinetic modulating chemotherapy plus irinotecan, or modified PMC) in a case of sigmoid colon cancer with local invasion and multiple hepatic metastases."	( [A case of hepatic metastasis from rectal carcinoma successfully treated with pharmacokinetic modulating chemotherapy (PMC)-CPT-11 therapy]. Chang, W; Kondo, Y; Kosaka, H; Maeda, S; Matsusaka, S; Okada, T; Oriyama, T, 2002)	0.31
" Several pharmacokinetic and pharmacodynamic factors including cellular efflux, modulation of topoisomerases I and II, lactone stability, alterations in metabolism, and drug-drug interactions, influence the antitumor response and toxicity of these agents."	( Cellular, pharmacokinetic, and pharmacodynamic aspects of response to camptothecins: can we improve it? Jung, LL; Zamboni, WC, 2001)	0.54
"Population pharmacokinetic-dynamic analysis was prospectively integrated in a broad phase II program of lurtotecan (GI147211), a novel camptothecin derived topoisomerase I inhibitor, to determine the population pharmacokinetic profile in a larger population, to estimate individual pharmacokinetic parameters and to investigate relationships with clinical outcome."	( Population pharmacokinetic and dynamic analysis of the topoisomerase I inhibitor lurtotecan in phase II studies. Calvert, H; Cortes-Funes, H; Dombernowsky, P; Gamucci, T; Gore, ME; Hanauske, AR; Heinrich, B; Kaye, SB; Lehnert, M; Loos, WJ; Paridaens, R; Pavlidis, N; Roelvink, M; Schellens, JH; Selinger, K; Sessa, C; van Oosterom, AT; Verweij, J; Wanders, J; Wissel, PS, 2002)	0.52
" He was treated postoperatively with arterial infusion pharmacokinetic modulating chemotherapy (PMC) and venous infusion CPT-11 (modified PMC)."	( [A case of rectal cancer with multiple liver metastases that responded dramatically to pharmacokinetic modulating chemotherapy/CPT-11 therapy]. Dan, T; Kitayama, Y; Kosaka, H; Maeda, S; Matsusaka, S; Okada, T; Tanabe, H; Yamasaki, H, 2002)	0.31
"A phase II trial was instigated to investigate the antitumour activity, the safety and the pharmacokinetic parameters of RFS2000, a recently identified oral topoisomerase I inhibitor, given once daily (1."	( Multicentre phase II and pharmacokinetic study of RFS2000 (9-nitro-camptothecin) administered orally 5 days a week in patients with glioblastoma multiforme. Campone, M; Chollet, P; Fety-Deporte, R; Fumoleau, P; Lacombe, D; Lesimple, T; Menten, J; Paoletti, X; Raymond, E; Stupp, R, 2002)	0.55
"We have shown previously that the terminal disposition half-life of SN-38, the active metabolite of irinotecan, is much longer than earlier thought."	( Irinotecan pharmacokinetics-pharmacodynamics: the clinical relevance of prolonged exposure to SN-38. de Bruijn, P; Loos, WJ; Mathijssen, RH; Nooter, K; Sparreboom, A; Verweij, J, 2002)	0.31
"To build population pharmacokinetic (PK) models for irinotecan (CPT-11) and its currently identified metabolites."	( Clinical pharmacokinetics of irinotecan and its metabolites: a population analysis. Karlsson, MO; Mathijssen, RH; Sparreboom, A; Verweij, J; Xie, R, 2002)	0.31
"The interconversion between the lactone and carboxylate forms of CPT-11 was relatively rapid, with an equilibration half-life of 14 minutes in the central compartment and hydrolysis occurring at a rate five times faster than lactonization."	( Clinical pharmacokinetics of irinotecan and its metabolites: a population analysis. Karlsson, MO; Mathijssen, RH; Sparreboom, A; Verweij, J; Xie, R, 2002)	0.31
" The aims of the study were to evaluate the linearity of CPT-11 pharmacokinetics and the influence of the schedule of administration of CPT-11 in mice, using a population pharmacokinetic approach with the NON-linear Mixed Effects Model (NONMEM) program."	( Non-linear pharmacokinetics of irinotecan in mice. Canal, P; Chatelut, E; Guichard, S; Rouits, E, 2002)	0.31
"Our objective was to build population pharmacokinetic models that describe plasma concentrations of irinotecan (CPT-11) and its metabolites 7-ethyl-10-hydroxycamptothecin (SN-38) and SN-38 glucuronide (SN-38G) and to investigate the pharmacokinetic-pharmacodynamic relationships between drug exposure and diarrhea, the major dose-limiting toxicity."	( Clinical pharmacokinetics of irinotecan and its metabolites in relation with diarrhea. Karlsson, MO; Mathijssen, RH; Sparreboom, A; Verweij, J; Xie, R, 2002)	0.51
" The population pharmacokinetic models were developed to describe plasma concentration-time profiles."	( Clinical pharmacokinetics of irinotecan and its metabolites in relation with diarrhea. Karlsson, MO; Mathijssen, RH; Sparreboom, A; Verweij, J; Xie, R, 2002)	0.31
"A 3-compartment pharmacokinetic model best described the disposition of irinotecan, whereas SN-38 and SN-38G showed 2-compartmental characteristics."	( Clinical pharmacokinetics of irinotecan and its metabolites in relation with diarrhea. Karlsson, MO; Mathijssen, RH; Sparreboom, A; Verweij, J; Xie, R, 2002)	0.31
"Polymeric drug conjugates are a new and experimental class of drug delivery systems with pharmacokinetic promises."	( A phase I and pharmacokinetic study of MAG-CPT, a water-soluble polymer conjugate of camptothecin. Beijnen, JH; Breda, M; Fraier, D; Grazia Porro, M; Jansen, S; Lieverst, J; Pellizzoni, C; Rosing, H; Schellens, JH; Schoemaker, NE; Spinelli, R; Swart, M; ten Bokkel Huinink, WW; van Kesteren, C, 2002)	0.54
" No pharmacologic interactions were observed between these agents, and no correlations between pharmacokinetic parameters and toxicity were noted."	( Phase I and pharmacokinetic study of irinotecan in combination with raltitrexed. Adams, AL; Brady, D; Engstrom, PF; Gallo, JM; Kilpatrick, D; Lewis, NL; Litwin, S; Meropol, NJ; Scher, R; Szarka, CE; Weiner, LM, 2002)	0.31
"To determine the recommended dose (RD) and the pharmacokinetic profile of irinotecan and its metabolites in cancer patients with hyperbilirubinemia."	( Dosage adjustment and pharmacokinetic profile of irinotecan in cancer patients with hepatic dysfunction. Armand, JP; Boige, V; Ducreux, M; Faivre, S; Gatineau, M; Jacques, C; Raymond, E; Rixe, O; Sanderink, GJ; Vernillet, L, 2002)	0.31
" Pharmacokinetic analysis showed that the relative increase in exposure was likely caused by reduced biliary excretion."	( Dosage adjustment and pharmacokinetic profile of irinotecan in cancer patients with hepatic dysfunction. Armand, JP; Boige, V; Ducreux, M; Faivre, S; Gatineau, M; Jacques, C; Raymond, E; Rixe, O; Sanderink, GJ; Vernillet, L, 2002)	0.31
" Population pharmacokinetic analysis of both the parent and the metabolite was performed using the nonlinear mixed effect modelling program (NONMEM)."	( Development of an optimal pharmacokinetic sampling schedule for rubitecan administered orally in a daily times five schedule. Beijnen, JH; Mathôt, RA; Rosing, H; Schellens, JH; Schoemaker, NE; Schöffski, P, 2002)	0.31
" Interindividual variability of the pharmacokinetic parameters ranged from 38% to 49%."	( Development of an optimal pharmacokinetic sampling schedule for rubitecan administered orally in a daily times five schedule. Beijnen, JH; Mathôt, RA; Rosing, H; Schellens, JH; Schoemaker, NE; Schöffski, P, 2002)	0.31
"An optimal sampling schedule was derived which allowed assessment of the pharmacokinetic parameters of both the parent compound and its metabolite 9-AC after oral administration of rubitecan."	( Development of an optimal pharmacokinetic sampling schedule for rubitecan administered orally in a daily times five schedule. Beijnen, JH; Mathôt, RA; Rosing, H; Schellens, JH; Schoemaker, NE; Schöffski, P, 2002)	0.31
"The objective of the study was to develop and validate a population pharmacokinetic model for irinotecan and 2 of its metabolites, SN-38 and SN-38 glucuronide (SN-38G)."	( Population pharmacokinetic model for irinotecan and two of its metabolites, SN-38 and SN-38 glucuronide. Atherton, PJ; Gupta, E; Kastrissios, H; Klein, CE; Pitot, HC; Ratain, MJ; Reid, JM; Sloan, JA, 2002)	0.31
" Pharmacokinetic parameter estimates were obtained by compartmental methods to describe the disposition of metabolites that are dependent on the disposition of the parent compound."	( Population pharmacokinetic model for irinotecan and two of its metabolites, SN-38 and SN-38 glucuronide. Atherton, PJ; Gupta, E; Kastrissios, H; Klein, CE; Pitot, HC; Ratain, MJ; Reid, JM; Sloan, JA, 2002)	0.31
"The validated population pharmacokinetic model describing the disposition of irinotecan and 2 of its metabolites should facilitate the design of future studies to elucidate the relative contributions of the parent compound and SN-38 to the pharmacologic and toxic effects of irinotecan therapy."	( Population pharmacokinetic model for irinotecan and two of its metabolites, SN-38 and SN-38 glucuronide. Atherton, PJ; Gupta, E; Kastrissios, H; Klein, CE; Pitot, HC; Ratain, MJ; Reid, JM; Sloan, JA, 2002)	0.31
" The study also sought to determine the maximum-tolerated dose (MTD) of PEG-CPT, characterize its pharmacokinetic behavior, and seek preliminary evidence of anticancer activity."	( A phase I and pharmacokinetic study of pegylated camptothecin as a 1-hour infusion every 3 weeks in patients with advanced solid malignancies. Denis, L; Forouzesh, B; Goetz, A; Hammond, LA; Kwiatek, J; McGuire, J; Ochoa, L; Patnaik, A; Rizzo, J; Rowinsky, EK; Schwartz, G; Takimoto, CH; Tolcher, AW, 2003)	0.57
"3 hours; the harmonic mean half-life (t(1/2)) of free CPT was long (t(1/2), 77."	( A phase I and pharmacokinetic study of pegylated camptothecin as a 1-hour infusion every 3 weeks in patients with advanced solid malignancies. Denis, L; Forouzesh, B; Goetz, A; Hammond, LA; Kwiatek, J; McGuire, J; Ochoa, L; Patnaik, A; Rizzo, J; Rowinsky, EK; Schwartz, G; Takimoto, CH; Tolcher, AW, 2003)	0.57
" The characteristics of the myelosuppressive effects of PEG-CPT, the paucity of severe nonhematologic toxicities with repetitive treatment, the preliminary antitumor activity noted, and the slow clearance of CPT enabling simulation of desirable pharmacokinetic parameters with a convenient single-dosing regimen warrant further disease-directed evaluations."	( A phase I and pharmacokinetic study of pegylated camptothecin as a 1-hour infusion every 3 weeks in patients with advanced solid malignancies. Denis, L; Forouzesh, B; Goetz, A; Hammond, LA; Kwiatek, J; McGuire, J; Ochoa, L; Patnaik, A; Rizzo, J; Rowinsky, EK; Schwartz, G; Takimoto, CH; Tolcher, AW, 2003)	0.57
" To clarify the pharmacokinetic effects of different CPT-11 administration schedules, we compared two different regimens (continuous infusion of CPT-11 for 24 h and CPT-11 infusion for 90 min) combined with CDDP in patients with advanced gastric cancer."	( Pharmacokinetic study of two infusion schedules of irinotecan combined with cisplatin in patients with advanced gastric cancer. Fujitani, K; Hirao, M; Tsujinaka, T, 2003)	0.32
" Serial plasma and excreta samples were collected and the pharmacokinetic behavior of 9-NC in rats was characterized by specific liquid chromatographic assays."	( Pharmacokinetics of 9-nitro-20(S)-camptothecin in rats. Du, Y; Li, K; Xu, JH; Zhang, YF; Zhong, DF, 2003)	0.6
"To assess the safety and toxicity profile of escalating doses of intravenous irinotecan, in combination with a fixed dose of oral ciclosporin (Cs) and to determine the pharmacokinetic profile of irinotecan and its metabolites."	( Phase I and pharmacokinetic study of intravenous irinotecan plus oral ciclosporin in patients with fuorouracil-refractory metastatic colon cancer. Braun, MS; Button, CJ; Cheeseman, SL; Chester, JD; Davis, T; Hall, GD; Joel, SP; Perry, J; Seymour, MT, 2003)	0.32
" Pharmacokinetic analysis of plasma irinotecan and its metabolites SN38 and SN38G was performed during paired cycles with and without Cs."	( Phase I and pharmacokinetic study of intravenous irinotecan plus oral ciclosporin in patients with fuorouracil-refractory metastatic colon cancer. Braun, MS; Button, CJ; Cheeseman, SL; Chester, JD; Davis, T; Hall, GD; Joel, SP; Perry, J; Seymour, MT, 2003)	0.32
" Pharmacokinetic studies demonstrated that irinotecan clearance was reduced from 13."	( Phase I and pharmacokinetic study of intravenous irinotecan plus oral ciclosporin in patients with fuorouracil-refractory metastatic colon cancer. Braun, MS; Button, CJ; Cheeseman, SL; Chester, JD; Davis, T; Hall, GD; Joel, SP; Perry, J; Seymour, MT, 2003)	0.32
" Dose-limiting diarrhea was not seen during this study, supporting the hypothesis that pharmacokinetic modulation of irinotecan by Cs may improve its therapeutic index."	( Phase I and pharmacokinetic study of intravenous irinotecan plus oral ciclosporin in patients with fuorouracil-refractory metastatic colon cancer. Braun, MS; Button, CJ; Cheeseman, SL; Chester, JD; Davis, T; Hall, GD; Joel, SP; Perry, J; Seymour, MT, 2003)	0.32
"To assess the antitumour activity and safety profile of irinotecan and its pharmacokinetic interactions with anticonvulsants in patients with glioblastoma multiforme."	( Multicentre phase II study and pharmacokinetic analysis of irinotecan in chemotherapy-naïve patients with glioblastoma. Armand, JP; Boige, V; Fabbro, M; Faivre, S; Frenay, M; Germa, C; Raymond, E; Rixe, O; Rodier, JM; Sicard, E; Vassal, G; Vernillet, L, 2003)	0.32
"This multicentre phase II and pharmacokinetic study investigated the effects of irinotecan 350 mg/m(2) given as a 90-min infusion every 3 weeks either prior to (group A) or after relapse following radiotherapy (group B) in chemotherapy-naïve patients with glioblastoma."	( Multicentre phase II study and pharmacokinetic analysis of irinotecan in chemotherapy-naïve patients with glioblastoma. Armand, JP; Boige, V; Fabbro, M; Faivre, S; Frenay, M; Germa, C; Raymond, E; Rixe, O; Rodier, JM; Sicard, E; Vassal, G; Vernillet, L, 2003)	0.32
" There were no significant differences in the pharmacokinetic parameters of total CPT-11 between treatment groups (p>0."	( The modulation of irinotecan-induced diarrhoea and pharmacokinetics by three different classes of pharmacologic agents. Cheung, YB; Chowbay, B; Lee, EJ; Sharma, A; Zhou, QY, )	0.13
" For the 6 patients who received EIAs but whose SN-38 areas under the concentration-time curve (AUCs) on Day 1 were below clinically significant levels, irinotecan dosage was increased, and subsequent pharmacokinetic studies were performed."	( Effect of intrapatient dosage escalation of irinotecan on its pharmacokinetics in pediatric patients who have high-grade gliomas and receive enzyme-inducing anticonvulsant therapy. Bowers, DC; Chintagumpala, MM; Crews, KR; Gajjar, A; Jones-Wallace, D; Stewart, CF, 2003)	0.32
" DX-8951f had a terminal elimination half-life of approximately 8 h and a clearance of 2 l/h/m(2)."	( Phase I and pharmacokinetic study of the topoisomerase I inhibitor, exatecan mesylate (DX-8951f), using a weekly 30-minute intravenous infusion, in patients with advanced solid malignancies. Bates, NP; Boven, E; Braybrooke, JP; Cheverton, PD; Dobbs, N; Pinedo, HM; Ruijter, R; Talbot, DC, 2003)	0.32
" This was consistent with pharmacokinetic data indicating that the total body clearance (CL) of irinotecan in this patient population was considerably greater than in colorectal cancer patients."	( Phase I clinical and pharmacokinetic study of irinotecan in adults with recurrent malignant glioma. Batchelor, T; Fisher, JD; Gilbert, MR; Grossman, S; Lesser, G; Piantadosi, S; Supko, JG, 2003)	0.32
" Pharmacokinetic studies showed that the CL of irinotecan was distinctly dose dependent in the patients receiving EIAs, decreasing from approximately 50 liters/h/m(2) at the lower dose levels (125-238 mg/m(2)) to a mean +/- SD value of 29."	( Phase I clinical and pharmacokinetic study of irinotecan in adults with recurrent malignant glioma. Batchelor, T; Fisher, JD; Gilbert, MR; Grossman, S; Lesser, G; Piantadosi, S; Supko, JG, 2003)	0.32
" These findings have important implications for subsequent clinical trials to further evaluate irinotecan in brain cancer patients and underscore the importance of assessing the potential for pharmacokinetic interactions between concurrent medications and chemotherapeutic agents."	( Phase I clinical and pharmacokinetic study of irinotecan in adults with recurrent malignant glioma. Batchelor, T; Fisher, JD; Gilbert, MR; Grossman, S; Lesser, G; Piantadosi, S; Supko, JG, 2003)	0.32
"Irinotecan was administered to 65 cancer patients as a 90-min infusion (dose, 200-350 mg/m(2)), and pharmacokinetic data were obtained during the first cycle."	( Irinotecan pathway genotype analysis to predict pharmacokinetics. Baker, SD; Karlsson, MO; Marsh, S; Mathijssen, RH; McLeod, HL; Sparreboom, A; Verweij, J; Xie, R, 2003)	0.32
" Pharmacokinetic parameters were not related to any of the other multiple variant genotypes, possibly because of the low allele frequency."	( Irinotecan pathway genotype analysis to predict pharmacokinetics. Baker, SD; Karlsson, MO; Marsh, S; Mathijssen, RH; McLeod, HL; Sparreboom, A; Verweij, J; Xie, R, 2003)	0.32
" Pharmacokinetic and neurotoxicity assessments were performed at the cohort 2 MTD."	( Phase I and pharmacokinetic study of two different schedules of oxaliplatin, irinotecan, Fluorouracil, and leucovorin in patients with solid tumors. Adjei, AA; Ames, MM; Atherton, P; Erlichman, C; Galanis, E; Goetz, MP; Goldberg, RM; Pitot, H; Reid, JM; Rubin, J; Sloan, JA; Windebank, AJ, 2003)	0.32
" This analytic procedure has been applied to a pharmacokinetic study of HCPT in clinical patients and the pharmacokinetic parameters of one-compartment model are calculated."	( Liquid chromatography determination of 10-hydroxycamptothecin in human serum by a column-switching system containing a pre-column with restricted access media and its application to a clinical pharmacokinetic study. Fan, JJ; Jia, ZP; Jiang, NX; Ma, J; Wang, J; Wang, R; Xie, H; Zhang, Q, 2003)	0.57
"The developed assay can be used to determine pharmacokinetic parameters for CPT-11, SN-38, SN-38 G, APC, and NPC in plasma and saliva from patients with metastatic colorectal cancer."	( Sensitive HPLC-fluorescence method for irinotecan and four major metabolites in human plasma and saliva: application to pharmacokinetic studies. Astre, C; Bressolle, F; Culine, S; Malosse, F; Pinguet, F; Poujol, S; Ychou, M, 2003)	0.32
" The parameters of the pharmacodynamic model are related to the growth characteristics of the tumor, to the drug potency, and to the kinetics of the tumor cell death."	( Predictive pharmacokinetic-pharmacodynamic modeling of tumor growth kinetics in xenograft models after administration of anticancer agents. Cammia, C; Croci, V; De Nicolao, G; Germani, M; Magni, P; Pesenti, E; Poggesi, I; Rocchetti, M; Simeoni, M, 2004)	0.32
"Disappearance of the lactone form from the plasma was biexponential with a mean distribution half-life of 57."	( Plasma and cerebrospinal fluid pharmacokinetic study of BNP1350 in nonhuman primates. Aleksic, A; Berg, SL; Blaney, SM; Dauser, R; Hausheer, F; Kerr, JZ; McGuffey, L; Nuchtern, JG; Thompson, PA, 2004)	0.32
" In 8 patients, plasma levels of irinotecan and its metabolites SN-38 and SN-38 glucuronide (SN-38glu) were measured by high-performance liquid chromatography and main pharmacokinetic parameters, including steady-state concentration, area under the time-concentration curve, and clearance, were calculated and normalized to the dose level of 22."	( A phase I and pharmacokinetic study of irinotecan given as a 7-day continuous infusion in metastatic colorectal cancer patients pretreated with 5-fluorouracil or raltitrexed. Allegrini, G; Barbara, C; Cupini, S; Danesi, R; Del Tacca, M; Di Paolo, A; Falcone, A; Masi, G, 2004)	0.32
" The pharmacokinetic data provided evidence that continuous infusion increased the metabolism of irinotecan to SN-38 with respect to standard 30/90-min administration."	( A phase I and pharmacokinetic study of irinotecan given as a 7-day continuous infusion in metastatic colorectal cancer patients pretreated with 5-fluorouracil or raltitrexed. Allegrini, G; Barbara, C; Cupini, S; Danesi, R; Del Tacca, M; Di Paolo, A; Falcone, A; Masi, G, 2004)	0.32
"Weekly administration of docetaxel has demonstrated comparable efficacy together with a distinct toxicity profile with reduced myelosuppression, although pharmacokinetic data with weekly regimens are lacking."	( Comparative pharmacokinetics of weekly and every-three-weeks docetaxel. Baker, SD; Brahmer, JR; Carducci, MA; Lee, CK; Sparreboom, A; Verweij, J; Wolff, AC; Zabelina, Y; Zhao, M, 2004)	0.32
" With extended plasma sampling beyond 24 h post-infusion, docetaxel clearance was 18% lower and the terminal half-life was 5-fold longer."	( Comparative pharmacokinetics of weekly and every-three-weeks docetaxel. Baker, SD; Brahmer, JR; Carducci, MA; Lee, CK; Sparreboom, A; Verweij, J; Wolff, AC; Zabelina, Y; Zhao, M, 2004)	0.32
" He was treated with pharmacokinetic modulating chemotherapy (PMC) and low-dose CPT-11."	( [A case of highly advanced ascending colon cancer with multiple bone and liver metastases and pleuritis carcinomatosa treated with pharmacokinetic modulating chemotherapy and low-dose CPT-11]. Aihara, T; Fukuhara, A; Kouno, T; Murayama, M; Nakagawa, K; Nakamura, E; Niida, M; Nishimoto, Y; Nozaki, H; Syouda, S; Watanabe, Y; Yagyu, T; Yasuoka, H, 2004)	0.32
" Pharmacokinetic studies were performed on cycle 1 and 2 to assess the best sequence and detect any interaction between the two drugs."	( Oxaliplatin plus irinotecan and FU-FOL combination and pharmacokinetic analysis in advanced colorectal cancer patients. Adam, R; Bastian, G; Bismuth, H; Castaing, D; Gil-Delgado, MA; Guinet, F; Khayat, D; Rocher, MA; Spano, JP; Taillibert, S; Urien, S, 2004)	0.32
" However, subsequent pharmacodynamic studies of this agent have led to its withdrawal from clinical development."	( Phase I and pharmacokinetic (PK) study of MAG-CPT (PNU 166148): a polymeric derivative of camptothecin (CPT). Bissett, D; Cassidy, J; de Bono, JS; Fraier, D; Magnè, ML; Main, M; Muirhead, F; Pellizzoni, C; Porro, MG; Robson, L; Speed, W; Spinelli, R; Twelves, C, 2004)	0.54
" Blood samples for pharmacokinetic analysis were obtained on day 1 of the first and second cycles."	( A phase I study and pharmacokinetics of irinotecan (CPT-11) and paclitaxel in patients with advanced non-small cell lung cancer. Fujiwara, K; Hisamoto, A; Hosokawa, S; Hotta, K; Kiura, K; Kozuki, T; Kuyama, S; Satoh, K; Tabata, M; Tanimoto, M; Ueoka, H, 2004)	0.32
" In the pharmacokinetic analysis, the maximum concentration of paclitaxel was elevated in a dose-dependent manner."	( A phase I study and pharmacokinetics of irinotecan (CPT-11) and paclitaxel in patients with advanced non-small cell lung cancer. Fujiwara, K; Hisamoto, A; Hosokawa, S; Hotta, K; Kiura, K; Kozuki, T; Kuyama, S; Satoh, K; Tabata, M; Tanimoto, M; Ueoka, H, 2004)	0.32
" The half-life (t1/2) of conjugated DX-8951, released DX-8951, and G-DX-8951 in plasma, liver, and tumor tissue were 2-3 days."	( Pharmacokinetics of DE-310, a novel macromolecular carrier system for the camptothecin analog DX-8951f, in tumor-bearing mice. Masubuchi, N, 2004)	0.55
"In a previous analysis, it was shown that body-surface area (BSA) is not a predictor of irinotecan pharmacokinetic parameters."	( Flat-fixed dosing of irinotecan: influence on pharmacokinetic and pharmacodynamic variability. de Jong, FA; Mathijssen, RH; Sparreboom, A; Verweij, J; Xie, R, 2004)	0.32
" Irinotecan pharmacokinetic investigations were performed before ifosfamide (day 1), after 3 days of ifosfamide (day 3), and 9 days after the end of ifosfamide (day 12)."	( Effect of fractionated ifosfamide on the pharmacokinetics of irinotecan in pediatric patients with osteosarcoma. Crews, KR; Daw, NC; Liu, T; Rodriguez-Galindo, C; Santana, VM; Stewart, CF, 2004)	0.32
" The method was successfully used to quantify SN-38 in plasma and tissues samples for pharmacokinetic and tissue distribution studies of LE-SN38 in mice."	( A simple and sensitive LC/MS/MS assay for 7-ethyl-10-hydroxycamptothecin (SN-38) in mouse plasma and tissues: application to pharmacokinetic study of liposome entrapped SN-38 (LE-SN38). Abu-Qare, A; Ahmad, A; Ahmad, I; Guo, W; Khan, S; Wang, YF, 2005)	0.57
" Pharmacokinetic analysis showed that there was no interaction between oral irinotecan and capecitabine, and that body-surface area was not significantly contributing to the observed pharmacokinetic variability."	( Phase I and pharmacokinetic study of oral irinotecan given once daily for 5 days every 3 weeks in combination with capecitabine in patients with solid tumors. Assadourian, S; deJonge, MJ; Dumez, H; Eskens, FA; Sanderink, GJ; Selleslach, J; Semiond, D; Soepenberg, O; Sparreboom, A; ter Steeg, J; van Oosterom, AT; Verweij, J, 2005)	0.33
" Because pharmacokinetics revealed a drug terminal half-life exceeding the 2 weeks administration interval, the protocol was amended to a 6-week interval between administrations also based on available information from a parallel trial using an every 4 weeks schedule."	( Phase I and pharmacokinetic study of DE-310 in patients with advanced solid tumors. Cheverton, P; de Bruin, P; de Heus, G; de Jonge, MJ; Ducharme, MP; Eskens, FA; Soepenberg, O; Sparreboom, A; Verweij, J; Wanders, J, 2005)	0.33
" The apparent half-life of conjugated DX-8951, glycyl-DX-8951, and DX-8951 was 13 days."	( Phase I and pharmacokinetic study of DE-310 in patients with advanced solid tumors. Cheverton, P; de Bruin, P; de Heus, G; de Jonge, MJ; Ducharme, MP; Eskens, FA; Soepenberg, O; Sparreboom, A; Verweij, J; Wanders, J, 2005)	0.33
"To characterize the maximum-tolerated dose, recommended dose, dose-limiting toxicities (DLT), pharmacokinetic profile, and food effect of orally administered irinotecan formulated as new semisolid matrix capsules."	( Phase I pharmacokinetic, food effect, and pharmacogenetic study of oral irinotecan given as semisolid matrix capsules in patients with solid tumors. Assadourian, S; de Jong, FA; de Jonge, MJ; Dumez, H; Eskens, FA; Lefebvre, P; Sanderink, GJ; Selleslach, J; Soepenberg, O; Sparreboom, A; Ter Steeg, J; Thomas, J; van Oosterom, AT; van Schaik, RH; Verweij, J, 2005)	0.33
" This study confirms that oral administration of irinotecan is feasible and may have favorable pharmacokinetic characteristics."	( Phase I pharmacokinetic, food effect, and pharmacogenetic study of oral irinotecan given as semisolid matrix capsules in patients with solid tumors. Assadourian, S; de Jong, FA; de Jonge, MJ; Dumez, H; Eskens, FA; Lefebvre, P; Sanderink, GJ; Selleslach, J; Soepenberg, O; Sparreboom, A; Ter Steeg, J; Thomas, J; van Oosterom, AT; van Schaik, RH; Verweij, J, 2005)	0.33
" The current study, undertaken in 27 patients with gastrointestinal tumours, aimed to assess the toxicity and potential for significant pharmacokinetic interactions of a combination regimen incorporating capecitabine with 3-weekly irinotecan (XELIRI)."	( A phase I clinical and pharmacokinetic study of capecitabine (Xeloda) and irinotecan combination therapy (XELIRI) in patients with metastatic gastrointestinal tumours. Bertheault-Cvitkovic, F; Bugat, R; Canal, P; Chatelut, E; Cornen, X; Delord, JP; Dieras, V; Guimbaud, R; Lochon, I; Lokiec, F; Mery-Mignard, D; Mouri, Z; Pierga, JY; Turpin, FL, 2005)	0.33
" The pharmacokinetics of lactone and total (lactone + carboxylate) forms was determined on days 1 and 12 using a noncompartmental pharmacokinetic method."	( Safety, tolerability, and pharmacokinetics of a capsule formulation of DRF-1042, a novel camptothecin analog, in refractory cancer patients in a bridging phase I study. Chatterjee, A; Digumarti, R; Jiwatani, S; Katneni, K; Mamidi, RN; Mullangi, R; Srinivas, ML; Srinivas, NR; Surath, A; Uppalapati, S; Upreti, VV, 2005)	0.55
" The objectives of this study were to determine the maximal tolerated dose (MTD) of the combination of docetaxel and irinotecan administered weekly for four consecutive weeks every 42 days, to describe toxicities of this regimen, and to perform a pharmacokinetic analysis to evaluate changes in drug disposition as a function of dose as well as repeated dosing."	( Phase I clinical and pharmacokinetic trial of docetaxel and irinotecan administered on a weekly schedule. Beringer, P; Garcia, AA; Iqbal, S; Jeffers, S; Lenz, HJ; Louie, S; Pujari, M, 2005)	0.33
" There were no significant differences in pharmacokinetic parameters between day 1 and day 22 (n=20)."	( Phase I clinical and pharmacokinetic trial of docetaxel and irinotecan administered on a weekly schedule. Beringer, P; Garcia, AA; Iqbal, S; Jeffers, S; Lenz, HJ; Louie, S; Pujari, M, 2005)	0.33
" In this study, the effect of methylselenocysteine on pharmacokinetic and pharmacogenetic profiles of genes relevant to CPT-11 metabolic pathway was evaluated to identify possible mechanisms associated with the observed combinational synergy."	( Irinotecan pharmacokinetic and pharmacogenomic alterations induced by methylselenocysteine in human head and neck xenograft tumors. Azrak, RG; Cao, S; Durrani, FA; Li, X; McLeod, HL; Pendyala, L; Rustum, YM; Shannon, WD; Smith, PF; Yu, J, 2005)	0.33
" In addition, we aimed to explore the pharmacokinetic parameters of irinotecan and capecitabine when used in different sequences of administration, with irinotecan infusion either prior to or after the first intake of capecitabine."	( A phase I/II and pharmacokinetic study of irinotecan in combination with capecitabine as first-line therapy for advanced colorectal cancer. Bakker, JM; Falk, S; Groenewegen, G; Kerr, DJ; Maughan, T; Nortier, JW; Punt, CJ; Rea, DW; Richel, DJ; Semiond, D; Smit, JM; Steven, N; Ten Bokkel Huinink, WW, 2005)	0.33
" Pharmacokinetic analysis was performed in patients treated at the recommended dose in two cohorts of patients in which the sequence of the first administration of each drug was reversed."	( A phase I/II and pharmacokinetic study of irinotecan in combination with capecitabine as first-line therapy for advanced colorectal cancer. Bakker, JM; Falk, S; Groenewegen, G; Kerr, DJ; Maughan, T; Nortier, JW; Punt, CJ; Rea, DW; Richel, DJ; Semiond, D; Smit, JM; Steven, N; Ten Bokkel Huinink, WW, 2005)	0.33
" The pharmacokinetic data suggest that the sequence of administration does not impact significantly on the metabolism of the two drugs."	( A phase I/II and pharmacokinetic study of irinotecan in combination with capecitabine as first-line therapy for advanced colorectal cancer. Bakker, JM; Falk, S; Groenewegen, G; Kerr, DJ; Maughan, T; Nortier, JW; Punt, CJ; Rea, DW; Richel, DJ; Semiond, D; Smit, JM; Steven, N; Ten Bokkel Huinink, WW, 2005)	0.33
" The body weight loss, gastrointestinal and hematological toxicities induced by CPT-11, and the pharmacokinetic parameters of CPT-11 were evaluated in rats pretreated with SJW or vehicle."	( St. John's Wort modulates the toxicities and pharmacokinetics of CPT-11 (irinotecan) in rats. Chan, E; Chan, SY; Chen, X; Duan, W; Ho, PC; Hu, Z; Huang, M; Li, X; Xu, C; Yang, H; Yang, X; Zhou, S; Zhu, YZ, 2005)	0.33
"This trial assessed pharmacokinetic interactions between cetuximab and irinotecan."	( Pharmacokinetic profile of cetuximab (Erbitux) alone and in combination with irinotecan in patients with advanced EGFR-positive adenocarcinoma. Bonnay, M; Delbaldo, C; Dieras, V; Faivre, S; Kovar, A; Laurence, V; Mueser, M; Nolting, A; Pierga, JY; Raymond, E; Vedovato, JC, 2005)	0.33
" Both CPT-11 and CCB need to be activated by human carboxyl esterases, therefore a probable pharmacokinetic drug interaction was checked."	( Pharmacokinetics and metabolism of irinotecan combined with capecitabine in patients with advanced colorectal cancer. Czejka, M; Hauer, K; Ostermann, E; Schueller, J, )	0.13
"We studied the toxicities, potential pharmacokinetic interactions, and preliminary antitumor activity of the combination of docetaxel and irinotecan with celecoxib, a selective cyclooxygenase-2 inhibitor."	( Phase I and pharmacokinetic study of docetaxel, irinotecan, and celecoxib in patients with advanced non-small cell lung cancer. Argiris, A; Avram, MJ; Kut, V; Luong, L, 2006)	0.33
" The alteration of irinotecan pharmacokinetic parameters observed may not be clinically relevant."	( Phase I and pharmacokinetic study of docetaxel, irinotecan, and celecoxib in patients with advanced non-small cell lung cancer. Argiris, A; Avram, MJ; Kut, V; Luong, L, 2006)	0.33
" The plasma half-life of IT-101 ranges from 17 -20 h and is significantly greater than that of CPT alone (1."	( Pharmacokinetics and biodistribution of the camptothecin-polymer conjugate IT-101 in rats and tumor-bearing mice. Cheng, J; Davis, ME; Khin, KT; Schluep, T, 2006)	0.59
"The studies presented here indicate that intravenous administration of IT-101, a cyclodextrin based polymer-CPT conjugate, gives prolonged plasma half-life and enhanced distribution to tumor tissue when compared to CPT alone."	( Pharmacokinetics and biodistribution of the camptothecin-polymer conjugate IT-101 in rats and tumor-bearing mice. Cheng, J; Davis, ME; Khin, KT; Schluep, T, 2006)	0.59
"The novel fluoro-substituted camptothecin analog, BMS-286309, and its prodrug, BMS-422461, were evaluated for their pharmacologic, toxicologic, metabolic and pharmacokinetic developmental potential."	( Novel fluoro-substituted camptothecins: in vivo antitumor activity, reduced gastrointestinal toxicity and pharmacokinetic characterization. Balasubramanian, BN; Fairchild, CR; Jang, GR; Long, B; Marathe, PH; Monticello, TM; Rose, WC; Wall, ME; Wani, MC, 2006)	0.93
"In vitro and in vivo assays were used to assess the compounds for topoisomerase I activity, antitumor activity, gastrointestinal (GI) toxicity, and pharmacokinetic parameters."	( Novel fluoro-substituted camptothecins: in vivo antitumor activity, reduced gastrointestinal toxicity and pharmacokinetic characterization. Balasubramanian, BN; Fairchild, CR; Jang, GR; Long, B; Marathe, PH; Monticello, TM; Rose, WC; Wall, ME; Wani, MC, 2006)	0.64
" The pharmacokinetic profile in rat blood demonstrated that BMS-422461 was rapidly cleaved to BMS-286309."	( Novel fluoro-substituted camptothecins: in vivo antitumor activity, reduced gastrointestinal toxicity and pharmacokinetic characterization. Balasubramanian, BN; Fairchild, CR; Jang, GR; Long, B; Marathe, PH; Monticello, TM; Rose, WC; Wall, ME; Wani, MC, 2006)	0.64
"The favorable in vivo metabolic activation of BMS-422461, and the pharmacokinetic characteristics of BMS-286309, suggest that the good efficacy of BMS-422461 is derived from robust in vivo release of BMS-286309 in rodents and the likelihood that this biotransformation will be preserved in humans."	( Novel fluoro-substituted camptothecins: in vivo antitumor activity, reduced gastrointestinal toxicity and pharmacokinetic characterization. Balasubramanian, BN; Fairchild, CR; Jang, GR; Long, B; Marathe, PH; Monticello, TM; Rose, WC; Wall, ME; Wani, MC, 2006)	0.64
" These results indicate that bevacizumab can be safely administered in combination with the Saltz regimen without pharmacokinetic interaction."	( Concomitant administration of bevacizumab, irinotecan, 5-fluorouracil, and leucovorin: nonclinical safety and pharmacokinetics. Bricarello, A; Christian, BJ; Gaudreault, J; Mounho, B; Shiu, V; Zuch, CL, )	0.13
" Diflomotecan showed linear pharmacokinetic behaviour and the selected PK/PD model described adequately the time course of neutropenia."	( Phase I dose-finding study and a pharmacokinetic/pharmacodynamic analysis of the neutropenic response of intravenous diflomotecan in patients with advanced malignant tumours. Cendrós, JM; Garrido, MJ; Obach, R; Peraire, C; Principe, P; Segura, C; Trocòniz, IF, 2006)	0.33
" Pharmacokinetic studies of irinotecan and its metabolites 7-ethyl-10-hydroxycamptothecin (SN-38), 7-ethyl-10-[3,4,5-trihydroxy-pyran-2-carboxylic acid]-camptothecin (SN-38-glucuronide), and 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]-carbonyloxycamptothecin were done during the first three irinotecan administrations."	( Effect of milk thistle (Silybum marianum) on the pharmacokinetics of irinotecan. Baker, SD; Gelderblom, H; Guchelaar, HJ; Nortier, JW; Rudek, MA; Sparreboom, A; van Erp, NP; Zhao, M, 2005)	0.56
"Forty patients and 75 pharmacokinetic time-courses were available for analysis."	( Pharmacokinetic modelling of 5-FU production from capecitabine--a population study in 40 adult patients with metastatic cancer. Lokiec, F; Rezaí, K; Urien, S, 2005)	0.33
" Pharmacokinetic analysis was performed using non-compartmental analysis."	( Pharmacokinetics of lactone, carboxylate and total 9-nitrocamptothecin with different doses and administration routes in rats. Chen, J; Chu, X; Guo, J; Ping, Q; Song, M, 2006)	0.58
"To assess the feasibility and antitumor activity of oblimersen sodium, an antisense oligonucleotide directed to the Bcl-2 mRNA, combined with irinotecan in patients with advanced colorectal carcinoma, characterize the pharmacokinetic behavior of both oblimersen sodium and irinotecan, and examine Bcl-2 protein inhibition in peripheral blood mononuclear cells (PBMC)."	( A phase I, pharmacokinetic and biologic correlative study of oblimersen sodium (Genasense, G3139) and irinotecan in patients with metastatic colorectal cancer. Berg, K; Hammond, LA; Izbicka, E; Kuhn, J; Mita, MM; Ochoa, L; Patnaik, A; Rowinsky, EK; Schwartz, G; Tolcher, AW; Yeh, IT, 2006)	0.33
" For irinotecan, SN-38, APC and NPC, similar pharmacokinetic profiles were observed from plasma and saliva data."	( Pharmacokinetics and pharmacodynamics of irinotecan and its metabolites from plasma and saliva data in patients with metastatic digestive cancer receiving Folfiri regimen. Abderrahim, AG; Astre, C; Bressolle, F; Duffour, J; Pinguet, F; Poujol, S; Ychou, M, 2006)	0.33
"To study the pharmacokinetic of 10-Hydroxycamptothecin HCPT by intraperitoneal administration."	( [Pharmacokinetic study of intraperitoneal chemotherapy with HCPT]. Jin, W; Li, N; Lin, XX; Lou, F; Pan, HM; Wu, JM; Ye, M; Zheng, Y, 2005)	0.59
" Pharmacokinetic studies were done for selenium and irinotecan and its metabolites."	( A phase I and pharmacokinetic study of fixed-dose selenomethionine and irinotecan in solid tumors. Azrak, RG; Badmaev, V; Creaven, PJ; Fakih, MG; Lawrence, D; Pendyala, L; Prey, JD; Reid, ME; Rustum, YM; Smith, PF, 2006)	0.33
" The long half-life of selenium resulted in a prolonged accumulation towards steady-state concentrations."	( A phase I and pharmacokinetic study of fixed-dose selenomethionine and irinotecan in solid tumors. Azrak, RG; Badmaev, V; Creaven, PJ; Fakih, MG; Lawrence, D; Pendyala, L; Prey, JD; Reid, ME; Rustum, YM; Smith, PF, 2006)	0.33
" Clinical pharmacokinetic studies have revealed substantial interindividual variabilities regarding the area under the concentration-time curve values and steady-state concentrations for all drugs reviewed in this article."	( Camptothecin and podophyllotoxin derivatives: inhibitors of topoisomerase I and II - mechanisms of action, pharmacokinetics and toxicity profile. Hartmann, JT; Lipp, HP, 2006)	1.78
" Pharmacokinetic parameters were recorded for 46 patients."	( A phase I dose-finding clinical pharmacokinetic study of an oral formulation of irinotecan (CPT-11) administered for 5 days every 3 weeks in patients with advanced solid tumours. Assadourian, S; Awada, A; de Boeck, G; de Bruijn, EA; Dumez, H; Guetens, G; Maes, RA; Piccart, M; Semiond, D; van Oosterom, A, 2006)	0.33
" The pharmacokinetic analysis were performed on 16 patients."	( Irinotecan in combination with thalidomide in patients with advanced solid tumors: a clinical study with pharmacodynamic and pharmacokinetic evaluation. Allegrini, G; Amatori, F; Bocci, G; Cerri, E; Cupini, S; Danesi, R; Del Tacca, M; Di Paolo, A; Falcone, A; Marcucci, L; Masi, G, 2006)	0.33
" This study aimed to investigate whether combination of thalidomide modulated the toxicities of CPT-11 using a rat model and the possible role of the altered pharmacokinetic component in the toxicity modulation using in vitro models."	( Pharmacokinetic mechanisms for reduced toxicity of irinotecan by coadministered thalidomide. Bian, JS; Boelsterli, UA; Chan, E; Chan, SY; Chen, YZ; Duan, W; Ho, PC; Hu, ZP; Huang, M; Ng, KY; Yang, XX; Zhou, SF, 2006)	0.33
" As a result, the PEG5000-PHDCA niosomes had the least phagocytic uptake, the longest half-life of 11."	( Stealth PEG-PHDCA niosomes: effects of chain length of PEG and particle size on niosomes surface properties, in vitro drug release, phagocytic uptake, in vivo pharmacokinetics and antitumor activity. Fang, C; Pei, Y; Shi, B, 2006)	0.33
" This is because of the different pharmacokinetic parameters of systemically administered chemotherapeutic agents between the brain and the rest of the body."	( Pharmacokinetic considerations in the treatment of CNS tumours. Motl, S; Stewart, CF; Waters, CM; Zhuang, Y, 2006)	0.33
" Endpoints included pharmacokinetic analyses of 9-NC and etoposide, and treatment-induced modulations of topo I and II expression in peripheral blood mononuclear cells."	( Sequential oral 9-nitrocamptothecin and etoposide: a pharmacodynamic- and pharmacokinetic-based phase I trial. Antonia, S; Cantor, A; Fishman, M; Garrett, C; Gump, J; Lush, RM; Munster, PN; Rocha-Lima, C; Simon, GR; Sullivan, DM; Tetteh, L; Williams, C, 2006)	0.64
" Only 2+/-1% of 9-AC released from the polymer conjugate was detected in the small intestine (SI), and the mean peak concentration of free 9-AC was 45-fold higher than that from released drug."	( Biodistribution and pharmacokinetics of colon-specific HPMA copolymer--9-aminocamptothecin conjugate in mice. Gao, SQ; Kopecek, J; Kopecková, P; Lu, ZR, 2007)	0.57
" The study also sought to detect major pharmacokinetic drug-drug interactions between these agents and preliminary evidence of antitumor activity in patients with advanced solid malignancies."	( A phase I and pharmacokinetic study of pemetrexed plus irinotecan in patients with advanced solid malignancies. Beeram, M; Chu, Q; De Bono, J; Forouzesh, B; Hammond, LA; Hong, S; John, W; Latz, JE; Nguyen, B; Rowinsky, EK; Schwartz, G, 2007)	0.34
" No major pharmacokinetic interactions between the agents were evident."	( A phase I and pharmacokinetic study of pemetrexed plus irinotecan in patients with advanced solid malignancies. Beeram, M; Chu, Q; De Bono, J; Forouzesh, B; Hammond, LA; Hong, S; John, W; Latz, JE; Nguyen, B; Rowinsky, EK; Schwartz, G, 2007)	0.34
" Secondary objectives were to determine the safety and pharmacokinetic (PK) profile, and to make a preliminary assessment of antitumour activity."	( A multicentre phase I and pharmacokinetic study of BN80915 (diflomotecan) administered daily as a 20-min intravenous infusion for 5 days every 3 weeks to patients with advanced solid tumours. de Jonge, MJ; McGovern, D; Obach, R; Principe, P; Scott, L; Soepenberg, O; Th Planting, AS; Twelves, C; Verweij, J, 2007)	0.34
" Pharmacokinetic analyses were performed during both treatments."	( Medicinal cannabis does not influence the clinical pharmacokinetics of irinotecan and docetaxel. de Bruijn, P; de Jong, FA; Engels, FK; Kitzen, JJ; Loos, WJ; Mathijssen, RH; Mathot, RA; Sparreboom, A; Verweij, J, 2007)	0.34
"The purpose of this study was to investigate the maximum tolerated doses, dose-limiting toxicities, efficacy, and pharmacokinetic profiles in the combination of irinotecan and paclitaxel."	( Phase I and pharmacokinetic study of combination chemotherapy using irinotecan and paclitaxel in patients with lung cancer. Asai, G; Fukuoka, M; Kurata, T; Nakagawa, K; Tamura, K; Uejima, H; Yamamoto, N, 2006)	0.33
" The long half-life (292."	( Phase I and pharmacokinetic study of UCN-01 in combination with irinotecan in patients with solid tumors. Baker, SD; Carducci, MA; Dancey, J; Donehower, RC; Hidalgo, M; Jimeno, A; Laheru, DA; Messersmith, WA; Purcell, T; Rudek, MA, 2008)	0.35
"Associations between UGT1A haplotypes and the area under concentration curve ratio (SN-38 glucuronide/SN-38) or toxicities were analyzed in 177 Japanese cancer patients treated with irinotecan as a single agent or in combination chemotherapy."	( Irinotecan pharmacokinetics/pharmacodynamics and UGT1A genetic polymorphisms in Japanese: roles of UGT1A1*6 and *28. Hamaguchi, T; Kaniwa, N; Kubota, K; Minami, H; Ohmatsu, H; Ohtsu, A; Ozawa, S; Saeki, M; Sai, K; Saijo, N; Saito, Y; Sawada, J; Shirao, K; Suzuki, K; Yamada, Y; Yamamoto, N; Yoshida, T, 2007)	0.34
"Among diplotypes of UGT1A genes, patients with the haplotypes harboring UGT1A1*6 or *28 had significantly reduced area under concentration curve ratios, with the effects of UGT1A1*6 or *28 being of a similar scale."	( Irinotecan pharmacokinetics/pharmacodynamics and UGT1A genetic polymorphisms in Japanese: roles of UGT1A1*6 and *28. Hamaguchi, T; Kaniwa, N; Kubota, K; Minami, H; Ohmatsu, H; Ohtsu, A; Ozawa, S; Saeki, M; Sai, K; Saijo, N; Saito, Y; Sawada, J; Shirao, K; Suzuki, K; Yamada, Y; Yamamoto, N; Yoshida, T, 2007)	0.34
"The haplotypes significantly associated with reduced area under concentration curve ratios and neutropenia contained UGT1A1*6 or *28, and both of them should be genotyped before irinotecan is given to Japanese and probably other Asian patients."	( Irinotecan pharmacokinetics/pharmacodynamics and UGT1A genetic polymorphisms in Japanese: roles of UGT1A1*6 and *28. Hamaguchi, T; Kaniwa, N; Kubota, K; Minami, H; Ohmatsu, H; Ohtsu, A; Ozawa, S; Saeki, M; Sai, K; Saijo, N; Saito, Y; Sawada, J; Shirao, K; Suzuki, K; Yamada, Y; Yamamoto, N; Yoshida, T, 2007)	0.34
" Toxicity and pharmacokinetic results were evaluated during courses 1 and 2 of irinotecan therapy."	( UGT1A1 promoter genotype correlates with SN-38 pharmacokinetics, but not severe toxicity in patients receiving low-dose irinotecan. Billups, C; Fraga, CH; Furman, WL; Gajjar, A; Liu, T; McGregor, LM; O'Shaughnessy, MA; Owens, T; Panetta, JC; Rodriguez-Galindo, C; Stewart, CF; Throm, SL, 2007)	0.34
" The clinical consequences of these substantial pharmacokinetic changes should be investigated."	( Lopinavir-ritonavir dramatically affects the pharmacokinetics of irinotecan in HIV patients with Kaposi's sarcoma. Corona, G; Innocenti, F; Sandron, S; Sartor, I; Tirelli, U; Toffoli, G; Vaccher, E, 2008)	0.35
" Co-administration of lapatinib increased the area under the plasma concentration-time curve of SN-38, the active metabolite of irinotecan, by an average of 41%; no other pharmacokinetic interactions were observed."	( A phase I and pharmacokinetic study of lapatinib in combination with infusional 5-fluorouracil, leucovorin and irinotecan. Flaherty, KT; Fleming, RA; Kerr, DJ; Koch, KM; Middleton, MR; Midgley, RS; O'Dwyer, PJ; Pratap, SE; Smith, DA; Stevenson, JP; Versola, M; Ward, C, 2007)	0.34
" Here, we report on the pharmacokinetic and pharmacodynamic effects of this combination in a cancer patient."	( Irinotecan chemotherapy during valproic acid treatment: pharmacokinetic interaction and hepatotoxicity. de Jong, FA; Kitzen, JJ; Loos, WJ; Mathijssen, RH; Mathôt, RA; van den Bent, MJ; van der Bol, JM; Verweij, J, 2007)	0.34
" Blood samples for pharmacokinetic purposes were drawn during a course with and a course without concomitant valproic acid."	( Irinotecan chemotherapy during valproic acid treatment: pharmacokinetic interaction and hepatotoxicity. de Jong, FA; Kitzen, JJ; Loos, WJ; Mathijssen, RH; Mathôt, RA; van den Bent, MJ; van der Bol, JM; Verweij, J, 2007)	0.34
"A pharmacokinetic model delineated the impact of GI transit, drug absorption rate, and first-pass metabolism on drug disposition following oral administration of HPMA copolymer-9-AC conjugate in rats."	( Pharmacokinetic modeling of absorption behavior of 9-aminocamptothecin (9-AC) released from colon-specific HPMA copolymer-9-AC conjugate in rats. Gao, SQ; Kopecek, J; Kopecková, P; Peterson, CM; Sun, Y, 2008)	0.59
" Therefore, to optimize the PEGylated system, we have developed a pharmacokinetic model to determine the relative importance of parameters involved in the distribution of drug-polymer conjugates after release from a polymer implant."	( Conjugation to increase treatment volume during local therapy: a case study with PEGylated camptothecin. Fleming, A; Haverstick, K; Mark Saltzman, W, )	0.35
"In this study we propose for the first time a limited sampling strategy to estimate the individual pharmacokinetic parameters of both irinotecan and SN-38 in patients treated with the irinotecan plus 5-fluorouracil (FOLFIRI) regimen."	( A limited sampling strategy to estimate the pharmacokinetic parameters of irinotecan and its active metabolite, SN-38, in patients with metastatic digestive cancer receiving the FOLFIRI regimen. Abderrahim, AG; Bressolle, FM; Duffour, J; Pinguet, F; Poujol, S; Ychou, M, 2007)	0.34
" Three sequential skin biopsies were obtained in selected patients to assess the pharmacodynamic effects on EGFR signaling of FOLFIRI alone and with EKB-569."	( Phase I pharmacokinetic/pharmacodynamic study of EKB-569, an irreversible inhibitor of the epidermal growth factor receptor tyrosine kinase, in combination with irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI) in first-line treatment of patients with Abbas, R; Andreu, J; Baselga, J; Casado, E; Cortes-Funes, H; Folprecht, G; Köhne, CH; Lejeune, C; Marimón, I; Paz-Ares, L; Quinn, S; Rojo, F; Salazar, R; Tabernero, J; Ubbelohde, U; Zacharchuk, C, 2008)	0.35
" Chemotherapy alone interferes with pharmacodynamic markers, an observation to be taken into account in future studies of targeted agents with chemotherapy."	( Phase I pharmacokinetic/pharmacodynamic study of EKB-569, an irreversible inhibitor of the epidermal growth factor receptor tyrosine kinase, in combination with irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI) in first-line treatment of patients with Abbas, R; Andreu, J; Baselga, J; Casado, E; Cortes-Funes, H; Folprecht, G; Köhne, CH; Lejeune, C; Marimón, I; Paz-Ares, L; Quinn, S; Rojo, F; Salazar, R; Tabernero, J; Ubbelohde, U; Zacharchuk, C, 2008)	0.35
"To define an integrated pharmacogenetic model for predicting irinotecan pharmacokinetic (PK) and severe toxicity, we evaluated multivariate analysis using 15 polymorphisms within seven genes with putative influence on metabolism and transport of irinotecan."	( Integrated pharmacogenetic prediction of irinotecan pharmacokinetics and toxicity in patients with advanced non-small cell lung cancer. Han, JY; Lee, JS; Lee, SY; Lim, HS; Park, YH, 2009)	0.35
" Before final applications of dendrimer-based drug delivery systems in humans, we should not only address the benefits of these systems, but also assess the long-term pharmacodynamic (PD) and pharmacokinetic (PK) behaviors and health risk of them."	( The effect of dendrimers on the pharmacodynamic and pharmacokinetic behaviors of non-covalently or covalently attached drugs. Cheng, Y; Xu, T, 2008)	0.35
"To develop a population pharmacokinetic model of irinotecan and its major metabolites in children with cancer and to identify covariates that predict variability in disposition."	( Pharmacokinetics of irinotecan and its metabolites in pediatric cancer patients: a report from the children's oncology group. Barrett, J; Bernstein, ML; Blaney, SM; Bomgaars, L; Gupta, M; Mondick, J; Rosner, GL; Thompson, PA; Yu, A, 2008)	0.35
"A population pharmacokinetic model was developed using plasma concentration data from 82 patients participating in a multicenter Pediatric Oncology Group (POG) single agent phase II clinical trial."	( Pharmacokinetics of irinotecan and its metabolites in pediatric cancer patients: a report from the children's oncology group. Barrett, J; Bernstein, ML; Blaney, SM; Bomgaars, L; Gupta, M; Mondick, J; Rosner, GL; Thompson, PA; Yu, A, 2008)	0.35
" Although genes involved in irinotecan pharmacokinetics have been shown to influence toxicity, there are no data on pharmacodynamic genes."	( Irinotecan pharmacogenetics: influence of pharmacodynamic genes. Altes, A; Baiget, M; Culverhouse, R; Hoskins, JM; Marcuello, E; Marsh, S; Maxwell, T; McLeod, HL; Paré, L; Van Booven, DJ, 2008)	0.35
"This is the first comprehensive pharmacogenetic investigation of irinotecan pharmacodynamic factors, and our findings suggest that genetic variation in the pharmacodynamic genes may influence the efficacy of irinotecan-containing therapies in advanced colorectal cancer patients."	( Irinotecan pharmacogenetics: influence of pharmacodynamic genes. Altes, A; Baiget, M; Culverhouse, R; Hoskins, JM; Marcuello, E; Marsh, S; Maxwell, T; McLeod, HL; Paré, L; Van Booven, DJ, 2008)	0.35
"To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of the combination of weekly oxaliplatin x 4, weekly irinotecan x 4 and capecitabine Monday through Friday for 4 weeks of every 6 week cycle in patients with solid tumors; to determine the pharmacokinetic profile of these agents in this combination; to observe patients for clinical anti-tumor response."	( Phase I clinical and pharmacokinetic study of oxaliplatin, irinotecan and capecitabine. Brell, JM; Cooney, MM; Dowlati, A; Egorin, MJ; Gibbons, J; Hoppel, CL; Ingalls, ST; Ivy, SP; Krishnamurthi, SS; Li, X; Overmoyer, BA; Remick, SC; Schluchter, MD; Weaver, KC; Zuhowski, EG, 2009)	0.35
"Enterohepatic recirculation of irinotecan and one of its metabolites, SN-38, has been observed in pharmacokinetic data sets from previous studies."	( Enterohepatic recirculation model of irinotecan (CPT-11) and metabolite pharmacokinetics in patients with glioma. Friedman, HS; Malone, S; Petros, WP; Schaaf, LJ; Younis, IR, 2009)	0.35
" Pharmacokinetic models were developed and tested for simultaneous fit of parent drug and metabolites, including a recirculation component."	( Enterohepatic recirculation model of irinotecan (CPT-11) and metabolite pharmacokinetics in patients with glioma. Friedman, HS; Malone, S; Petros, WP; Schaaf, LJ; Younis, IR, 2009)	0.35
"A recirculation chain incorporated in a multi-compartment pharmacokinetic model of irinotecan and its metabolites appears to improve characterization of this drug's disposition in patients with glioma."	( Enterohepatic recirculation model of irinotecan (CPT-11) and metabolite pharmacokinetics in patients with glioma. Friedman, HS; Malone, S; Petros, WP; Schaaf, LJ; Younis, IR, 2009)	0.35
" The pharmacokinetic data indicate that the area under the plasma concentration-time curves (AUC) of CPT-11 and SN-38 were increased by 57."	( Food-drug interaction of (-)-epigallocatechin-3-gallate on the pharmacokinetics of irinotecan and the metabolite SN-38. Lin, LC; Tsai, TH; Wang, MN, 2008)	0.35
" The purpose of this study was to further evaluate the safety and pharmacokinetic profile of a range of diflomotecan doses administered intravenously."	( A multi-centre dose-escalation and pharmacokinetic study of diflomotecan in patients with advanced malignancy. Cendros, JM; Evans, TR; Falk, S; Graham, JS; Samuel, LM, 2009)	0.35
" Pharmacokinetic analyses were performed on serial blood samples taken over the first 24 h after diflomotecan administration (cycles 1 and 2)."	( A multi-centre dose-escalation and pharmacokinetic study of diflomotecan in patients with advanced malignancy. Cendros, JM; Evans, TR; Falk, S; Graham, JS; Samuel, LM, 2009)	0.35
" Pharmacokinetic analyses revealed a less than dose-proportional increase in diflomotecan and for the two metabolites BN80942 and P-20, with a magnitude of P-20 exposure similar to the parent drug."	( A multi-centre dose-escalation and pharmacokinetic study of diflomotecan in patients with advanced malignancy. Cendros, JM; Evans, TR; Falk, S; Graham, JS; Samuel, LM, 2009)	0.35
"Diflomotecan administered as a 20-min intravenous infusion 3-weekly is characterised by a variable pharmacokinetic profile."	( A multi-centre dose-escalation and pharmacokinetic study of diflomotecan in patients with advanced malignancy. Cendros, JM; Evans, TR; Falk, S; Graham, JS; Samuel, LM, 2009)	0.35
" Because of the occurrence of toxicities due to the large interpatient variability in drug metabolism, irinotecan is a candidate for therapeutic drug monitoring and pharmacokinetic optimisation."	( Clinical pharmacokinetics of irinotecan-based chemotherapy in colorectal cancer patients. Bocci, G; Danesi, R; Del Tacca, M; Di Paolo, A, 2006)	0.33
" For a pharmacokinetic study, the concentration of 9-NC as the lactone form (9-NC."	( 9-nitrocamptothecin polymeric nanoparticles: cytotoxicity and pharmacokinetic studies of lactone and total forms of drug in rats. Dadashzadeh, S; Derakhshandeh, K; Shirazi, FH, 2008)	0.8
" In the present study, irinotecan showed an absolute bioavailability of 30% as calculated from the pharmacokinetic data."	( Development and validation of reversed phase liquid chromatographic method utilizing ultraviolet detection for quantification of irinotecan (CPT-11) and its active metabolite, SN-38, in rat plasma and bile samples: application to pharmacokinetic studies. Awasthi, A; Bansal, T; Jaggi, M; Khar, RK; Talegaonkar, S, 2008)	0.35
" Potential pharmacokinetic interactions and Topo-1 and DT-diaphorase (NQ01) gene expressions in peripheral-mononuclear cells were evaluated."	( Phase I and pharmacokinetic study of mitomycin C and celecoxib as potential modulators of tumor resistance to irinotecan in patients with solid malignancies. Drengler, R; Duan, W; Kolesar, JM; Kuhn, J; Otterson, G; Schaaf, LJ; Shapiro, C; Villalona-Calero, MA; Xu, Y, 2009)	0.35
" No relevant pharmacokinetic interactions occurred between irinotecan and MMC, and mean increases in Topo-1, were observed."	( Phase I and pharmacokinetic study of mitomycin C and celecoxib as potential modulators of tumor resistance to irinotecan in patients with solid malignancies. Drengler, R; Duan, W; Kolesar, JM; Kuhn, J; Otterson, G; Schaaf, LJ; Shapiro, C; Villalona-Calero, MA; Xu, Y, 2009)	0.35
"This study aims at establishing relationships between genetic and non-genetic factors of variation of the pharmacokinetics of irinotecan and its metabolites; and also at establishing relationships between the pharmacokinetic or metabolic parameters and the efficacy and toxicity of irinotecan."	( Pharmacokinetic and pharmacogenetic determinants of the activity and toxicity of irinotecan in metastatic colorectal cancer patients. Boisdron-Celle, M; Charasson, V; Chatelut, E; Delord, JP; Fonck, M; Gamelin, E; Laurand, A; Morel, A; Pétain, A; Poirier, AL; Robert, J; Rouits, E, 2008)	0.35
" Pharmacokinetic analysis was performed on plasma samples collected at the first cycle of treatment."	( A dose finding and pharmacokinetic study of capecitabine in combination with oxaliplatin and irinotecan in metastatic colorectal cancer. Antonuzzo, A; Bocci, G; Bursi, S; Chiara, S; Del Tacca, M; Di Paolo, A; Falcone, A; Fornaro, L; Loupakis, F; Masi, G; Pfanner, E; Vasile, E, 2009)	0.35
" Large interpatient variability in the pharmacokinetic parameters of investigated drugs was observed."	( A dose finding and pharmacokinetic study of capecitabine in combination with oxaliplatin and irinotecan in metastatic colorectal cancer. Antonuzzo, A; Bocci, G; Bursi, S; Chiara, S; Del Tacca, M; Di Paolo, A; Falcone, A; Fornaro, L; Loupakis, F; Masi, G; Pfanner, E; Vasile, E, 2009)	0.35
" Gimatecan has a very long apparent biological half-life (mean +/- SD, 77 +/- 37 h) and exists in plasma almost entirely as the pharmacologically active intact lactone form."	( Phase I and pharmacokinetic study of gimatecan given orally once a week for 3 of 4 weeks in patients with advanced solid tumors. Amato, A; Clark, JW; He, X; Lynch, TJ; Pace, S; Ready, N; Ryan, DP; Safran, H; Salem, N; Supko, JG; Zhu, AX; Zvereva, N, 2009)	0.35
" In addition, SN-38 showed significant change in oral pharmacokinetic parameters and minor changes in intravenous pharmacokinetic profile."	( Effect of P-glycoprotein inhibitor, verapamil, on oral bioavailability and pharmacokinetics of irinotecan in rats. Bansal, T; Jaggi, M; Khar, RK; Mishra, G; Talegaonkar, S, 2009)	0.35
" High interpatient variability occurred in the pharmacokinetic disposition of encapsulated and released CKD602."	( Phase I and pharmacokinetic study of pegylated liposomal CKD-602 in patients with advanced malignancies. Belani, CP; Edwards, RP; Friedland, DM; Maruca, L; Ramalingam, S; Ramanathan, RK; Stoller, RG; Strychor, S; Zamboni, BA; Zamboni, WC, 2009)	0.35
" Because the replacement of 2-day-infusional 5-fluorouracil (5-FU) of FOLFIRI with oral tegafur-uracil/leucovorin (UFT/LV) would be highly beneficial for clinical management, we performed a phase I trial using oral UFT/LV and a pharmacokinetic evaluation."	( Phase I and pharmacokinetic study of tegafur-uracil/leucovorin combined with 5-fluorouracil/leucovorin and irinotecan in patients with advanced colorectal cancer. Azuma, T; Chayahara, N; Hirai, M; Inoue, Y; Kadowaki, Y; Kasuga, M; Maeda, T; Miki, I; Nishisaki, H; Okumura, K; Okuno, T; Sakaeda, T; Tamura, T; Tsuda, M; Yamamori, M, 2009)	0.35
" Pharmacokinetic evaluation suggested continuous exposure to 5-FU by means of oral UFT/LV administration in this combination."	( Phase I and pharmacokinetic study of tegafur-uracil/leucovorin combined with 5-fluorouracil/leucovorin and irinotecan in patients with advanced colorectal cancer. Azuma, T; Chayahara, N; Hirai, M; Inoue, Y; Kadowaki, Y; Kasuga, M; Maeda, T; Miki, I; Nishisaki, H; Okumura, K; Okuno, T; Sakaeda, T; Tamura, T; Tsuda, M; Yamamori, M, 2009)	0.35
" Univariate and multivariate models of absolute neutrophil count (ANC) nadir and pharmacokinetic parameters were evaluated."	( Comprehensive pharmacogenetic analysis of irinotecan neutropenia and pharmacokinetics. Chen, P; Das, S; Dolan, ME; Innocenti, F; Kroetz, DL; Ramírez, J; Ratain, MJ; Relling, M; Rosner, GL; Schuetz, E, 2009)	0.35
" Coadministration of S-1 changed the pharmacokinetic behavior of CPT-11 and its metabolites."	( Effects of oral administration of S-1 on the pharmacokinetics of SN-38, irinotecan active metabolite, in patients with advanced colorectal cancer. Hamada, A; Saito, H; Sasaki, Y; Tazoe, K; Yokoo, K, 2009)	0.35
" The remaining material circulates in plasma with a terminal half-life of 13."	( Pharmacokinetics and tumor dynamics of the nanoparticle IT-101 from PET imaging and tumor histological measurements. Alabi, CA; Choi, CH; Czernin, J; Davis, ME; Hildebrandt, IJ; Hwang, J; Mack, BC; Schluep, T, 2009)	0.35
"A recent study found that variation in camptothecin pharmacodynamic genes (TOP1, PARP1, TDP1 and XRCC1) correlated with efficacy and risk of neutropenia in irinotecan-treated cancer patients (median dose: 180 mg/m2), which suggests that these genes might predict outcomes to irinotecan-based therapies."	( Pharmacodynamic genes do not influence risk of neutropenia in cancer patients treated with moderately high-dose irinotecan. Hoskins, JM; Innocenti, F; McLeod, HL; Ratain, MJ; Rosner, GL, 2009)	0.62
" Pharmacokinetic properties and antitumor activities of the two silatecans were studied and compared."	( Antitumor activities and pharmacokinetics of silatecans DB-67 and DB-91. Chang, CM; Chang, CY; Chang, JY; Chao, YS; Chen, CP; Chen, CT; Chuu, JJ; Huang, CL; Lee, TY; Li, CM; Lin, CT; Shen, CC; Wang, HS; Yeh, TK, 2010)	0.36
" This study is the first to evaluate the factors affecting the high interpatient variability in the pharmacokinetic disposition of S-CKD602."	( Pharmacokinetic study of pegylated liposomal CKD-602 (S-CKD602) in patients with advanced malignancies. Belani, CP; Edwards, RP; Friedland, DM; Maruca, L; Ramalingam, S; Ramanathan, RK; Stoller, RG; Strychor, S; Wu, H; Zamboni, BA; Zamboni, WC, 2009)	0.35
"This phase I dose-escalation study was designed to determine the maximum tolerated dose (MTD) and recommended dose of cetuximab administered on an every-second-week schedule to patients with metastatic colorectal cancer, on the basis of safety, pharmacokinetic and pharmacodynamic evaluation."	( Cetuximab administered once every second week to patients with metastatic colorectal cancer: a two-part pharmacokinetic/pharmacodynamic phase I dose-escalation study. Baselga, J; Cervantes, A; Ciardiello, F; Kisker, O; Liebscher, S; Macarulla, T; Martinelli, E; Ramos, FJ; Rivera, F; Rodriguez-Braun, E; Roselló, S; Tabernero, J; Vega-Villegas, ME, 2010)	0.36
" The half-life was 77."	( Clinical pharmacokinetics of the new oral camptothecin gimatecan: the inter-patient variability is related to alpha1-acid glycoprotein plasma levels. Bello, E; Carminati, P; Compagnoni, A; D'Incalci, M; Frapolli, R; Locatelli, A; Marsoni, S; Pisano, C; Rulli, E; Sessa, C; Viganò, L; Zucchetti, M, 2010)	0.62
" We characterized its pharmacokinetic profile in nude mice bearing human SK-N-DZ and TE-671 cell lines."	( Antitumor activity and pharmacokinetics of oral gimatecan on pediatric cancer xenografts. Cusano, G; D'Incalci, M; Di Francesco, AM; Forestieri, D; Meco, D; Patriarca, V; Pisano, C; Riccardi, R; Servidei, T; Zucchetti, M, 2010)	0.36
" Enzyme kinetic parameters (K(m) and V(max)) and pharmacokinetic properties of three probe drugs were compared using wild-type and humanized UGT1 mice that express the Gilbert's UGT1A1*28 allele [Tg(UGT1(A1*28)) Ugt1(-/-) mice]."	( A humanized UGT1 mouse model expressing the UGT1A1*28 allele for assessing drug clearance by UGT1A1-dependent glucuronidation. Cai, H; Chen, S; Hotz, K; La Placa, DB; Nguyen, N; Peterkin, V; Stevens, JC; Tukey, RH; Yang, YS, 2010)	0.36
" This method was used successfully to perform plasma pharmacokinetic studies of CPT11 after pulmonary artery embolization (PACE) in a sheep model."	( Simple liquid chromatography method for the quantification of irinotecan and SN38 in sheep plasma: application to in vivo pharmacokinetics after pulmonary artery chemoembolization using drug eluting beads. Baylatry, MT; Bengrine-Lefevre, L; Fernandez, C; Joly, AC; Laurent, A; Pelage, JP; Prugnaud, JL, 2010)	0.36
" The pharmacokinetics of CPT-11 and its metabolites were characterized using both traditional noncompartmental analysis and population pharmacokinetics using NONMEM VI; pharmacokinetic pharmacodynamic relationships of SN-38 with indices of toxicity were also evaluated."	( Pharmacokinetic and pharmacodynamic investigation of irinotecan hydrochloride in pediatric patients with recurrent or progressive solid tumors. Barrett, JS; Ida, K; Ishida, Y; Kaneko, M; Kashiwase, S; Kimura, T; Kumagai, M; Makimoto, A; Mugishima, H; Nagatoshi, Y; Taga, T, 2010)	0.36
" Pharmacokinetic parameters and consideration of relevant covariates (performance status (PS), BSA, corrected body weight (CBW), exponent of 3/4 on weight, etc."	( Pharmacokinetic and pharmacodynamic investigation of irinotecan hydrochloride in pediatric patients with recurrent or progressive solid tumors. Barrett, JS; Ida, K; Ishida, Y; Kaneko, M; Kashiwase, S; Kimura, T; Kumagai, M; Makimoto, A; Mugishima, H; Nagatoshi, Y; Taga, T, 2010)	0.36
" Pharmacokinetic modeling was used to estimate clearances, while simulations assessed the impact of clearance changes on overall AR-67 exposure."	( Factors affecting the in vivo lactone stability and systemic clearance of the lipophilic camptothecin analogue AR-67. Adane, ED; Anderson, BD; Leggas, M; Liu, Z; Xiang, TX, 2010)	0.58
" This norrnothermic IP OPT-11 pharmacokinetic study performed in a pig model confirms the possibility to achieve at least a 30 times higher peritoneal than systemic exposure."	( Pharmacokinetics of intraperitoneal irinotecan in a pig model. Drolet, P; Dubé, P; Sideris, L; Turcotte, S; Younan, R, 2010)	0.36
" We evaluated the relationship between monocyte and absolute neutrophil counts (ANCs) in the blood and pharmacokinetic disposition of S-CKD602 and nonliposomal CKD-602 (NL-CKD602) in patients."	( Bidirectional pharmacodynamic interaction between pegylated liposomal CKD-602 (S-CKD602) and monocytes in patients with refractory solid tumors. Bang, Y; Belani, CP; Edwards, RP; Friedland, DM; Kim, J; Lee, H; Maruca, LJ; Ramalingam, S; Ramanathan, RK; Stoller, RG; Strychor, S; Zamboni, BA; Zamboni, WC, 2011)	0.37
" The biliary excretion, intestinal damage, and pharmacokinetic study of CPT-11-loaded PEO-PPO-PEO micelles were investigated in rats."	( Effect of poly (ethylene oxide)-poly (propylene oxide)-poly (ethylene oxide) micelles on pharmacokinetics and intestinal toxicity of irinotecan hydrochloride: potential involvement of breast cancer resistance protein (ABCG2). Gan, L; Gan, Y; Guo, S; Zhang, X; Zhu, C, 2010)	0.36
" The aim of our study was to develop a population pharmacokinetic model for CPT-11 and SN-38 following the intraperitoneal (IP) administration of CPT-11."	( Population pharmacokinetics of CPT-11 (irinotecan) in gastric cancer patients with peritoneal seeding after its intraperitoneal administration. Ahn, BJ; Choi, MK; Kang, WK; Ko, JW; Lee, J; Lim, HY; Park, JO; Park, SH; Park, YS; Yim, DS, 2010)	0.36
" Several multicompartmental pharmacokinetic models were tested for CPT-11 and SN-38 in the sampled peritoneal fluid, plasma and urine."	( Population pharmacokinetics of CPT-11 (irinotecan) in gastric cancer patients with peritoneal seeding after its intraperitoneal administration. Ahn, BJ; Choi, MK; Kang, WK; Ko, JW; Lee, J; Lim, HY; Park, JO; Park, SH; Park, YS; Yim, DS, 2010)	0.36
"The 23 patients for a single-dose pharmacokinetic experiment were divided into 3 dosing cohorts."	( A phase I pharmacokinetics study of 9-nitrocamptothecin in patients with advanced solid tumors. Chen, P; Huang, C; Li, K; Liu, M; Wang, L; Xue, J; Yan, Z; Zhu, Z, 2011)	0.63
"In the single-dose pharmacokinetic study, the mean ± SD 9-nitrocamptothecin C(max) were 94."	( A phase I pharmacokinetics study of 9-nitrocamptothecin in patients with advanced solid tumors. Chen, P; Huang, C; Li, K; Liu, M; Wang, L; Xue, J; Yan, Z; Zhu, Z, 2011)	0.87
" A population pharmacokinetic (PK) model for encapsulated and released CKD-602 following administration of S-CKD602 was developed to assess factors that may influence S-CKD602 PK."	( Population pharmacokinetics of pegylated liposomal CKD-602 (S-CKD602) in patients with advanced malignancies. Bang, YJ; Belani, CP; Edwards, RP; Friedland, DM; Maruca, LJ; Ramalingam, S; Ramanathan, RK; Stoller, RG; Strychor, S; Wu, H; Zamboni, BA; Zamboni, WC, 2012)	0.38
" CPT13 in rat plasma was stable when stored at -20 °C or 4 °C for three freeze-thaw cycles, The method was employed for the first time during pharmacokinetic studies of CPT13 in rats following a single intravenous dose (0."	( Quantification of CPT13 in rat plasma using LC-MS/MS for a pharmacokinetic study. Deng, XQ; Gao, Y; Li, QY; Su, L; Wang, CC; Zhang, L; Zhu, QC; Zu, YG, 2011)	0.37
" We conducted a phase II trial to confirm the pharmacokinetic parameters from 3-Tesla dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as surrogate biomarkers of BV + FOLFIRI regimen efficacy in colorectal cancer with liver metastases."	( Pharmacokinetic parameters from 3-Tesla DCE-MRI as surrogate biomarkers of antitumor effects of bevacizumab plus FOLFIRI in colorectal cancer with liver metastasis. Akiyoshi, K; Hamaguchi, T; Hirashima, Y; Horita, Y; Kato, K; Miyake, M; Nakajima, T; Okita, N; Shimada, Y; Shirao, K; Takahari, D; Takashima, A; Tateishi, U; Yamada, Y, 2012)	0.38
" Because of the existence of some issues concerning the adoption of pharmacokinetic strategies to optimize CPT-11 dose and schedule, analyses of genetic polymorphisms seemed to offer a more reliable and safer approach for the identification of patients at risk than pharmacokinetics."	( Pharmacokinetic and pharmacogenetic predictive markers of irinotecan activity and toxicity. Bocci, G; Danesi, R; Del Re, M; Di Desidero, T; Di Paolo, A; Lastella, M; Polillo, M, 2011)	0.37
" Pharmacokinetic data when irinotecan was administered as a single agent in each arm were compared to data when the two study agents were co-administered using paired t tests."	( The effect of thalidomide on the pharmacokinetics of irinotecan and metabolites in advanced solid tumor patients. Cohen, EE; House, LK; Innocenti, F; Janisch, L; Karrison, T; Ramírez, J; Ratain, MJ; Wu, K, 2011)	0.37
"The differences in pharmacokinetic parameters and metabolic markers after thalidomide administration were small and unlikely to be clinically significant."	( The effect of thalidomide on the pharmacokinetics of irinotecan and metabolites in advanced solid tumor patients. Cohen, EE; House, LK; Innocenti, F; Janisch, L; Karrison, T; Ramírez, J; Ratain, MJ; Wu, K, 2011)	0.37
" The plasma concentration time profiles of HCPT fitted in two-compartment models well, and the main pharmacokinetic parameters found for HCPT after oral administration were as follows: Cmax 13."	( [Study on pharmacokinetics of HCPT nanosuspensions with ability of inhibiting P-gp in rats after oral administration]. He, Z; Pu, X; Sun, J; Sun, Y; Wang, Y; Zhang, P, 2011)	0.37
"Plasma pharmacokinetic (PK) studies were conducted following administration of AR-67 lactone or carboxylate doses alone or after pre-dosing with inhibitors of the efflux transporters P-gp and Bcrp."	( Pharmacokinetic modeling to assess factors affecting the oral bioavailability of the lactone and carboxylate forms of the lipophilic camptothecin analogue AR-67 in rats. Adane, ED; Anderson, BD; Leggas, M; Liu, Z; Xiang, TX, 2012)	0.58
" In view of a possible clinical development for loco-regional treatment of peritoneal carcinomatosis, this study aimed to establish the pharmacokinetic profile of Oncofid-S after single intraperitoneal or intravenous administration in the rat."	( Pharmacokinetic profile of Oncofid-S after intraperitoneal and intravenous administration in the rat. Bettella, F; Campisi, M; Greco, MC; Navarra, P; Renier, D; Tringali, G, 2012)	0.38
"The primary objective of this study is to evaluate the safety, tolerance, and pharmacokinetic profile of liver-directed therapy with drug-eluting beads irinotecan (DEBIRI) in combination with systemic modified FOLFOX in the treatment of unresectable liver metastases in chemotherapy-naive patients with colorectal cancer."	( Irinotecan drug-eluting beads in the treatment of chemo-naive unresectable colorectal liver metastasis with concomitant systemic fluorouracil and oxaliplatin: results of pharmacokinetics and phase I trial. Martin, RC; Metzger, T; Schreeder, M; Scoggins, CR; Sharma, V; Tatum, C; Tomalty, D, 2012)	0.38
" Pharmacokinetic data has demonstrated minimal detectable levels of irinotecan (18."	( Irinotecan drug-eluting beads in the treatment of chemo-naive unresectable colorectal liver metastasis with concomitant systemic fluorouracil and oxaliplatin: results of pharmacokinetics and phase I trial. Martin, RC; Metzger, T; Schreeder, M; Scoggins, CR; Sharma, V; Tatum, C; Tomalty, D, 2012)	0.38
" This method was successfully applied to perform brain and plasma pharmacokinetic studies of CPT-11 and SN-38 in mice after intraperitoneal administration."	( A new UPLC-MS/MS method for the determination of irinotecan and 7-ethyl-10-hydroxycamptothecin (SN-38) in mice: application to plasma and brain pharmacokinetics. Farinotti, R; Fernandez, C; Goldwirt, L; Lemaitre, F; Zahr, N, 2012)	0.6
" The AUC(0-∞) , elimination half-life and mean residence time of anionic submicron emulsions containing HCPT (HCPT-ASEs) and cationic submicron emulsions containing HCPT (HCPT-CSEs) were significantly greater than those of HCPT-I (P  <0."	( In-vivo pharmacokinetics, tissue distribution and anti-tumour effect of hydroxycamptothecin delivered in oil-in-water submicron emulsions. Liang, WQ; Liu, DX; Ye, ZW; Zhao, YX, 2012)	0.61
"Submicron emulsions can alter the pharmacokinetic characteristics and tissue distribution of HCPT, and enhance tumour targeting and anti-tumour activity."	( In-vivo pharmacokinetics, tissue distribution and anti-tumour effect of hydroxycamptothecin delivered in oil-in-water submicron emulsions. Liang, WQ; Liu, DX; Ye, ZW; Zhao, YX, 2012)	0.61
" Pharmacokinetic analyses suggest sorafenib and metabolite exposure correlate with OS and DLTs."	( Phase I pharmacokinetic and pharmacodynamic study of cetuximab, irinotecan and sorafenib in advanced colorectal cancer. Arcaroli, J; Azad, N; Carducci, MA; Dasari, A; Diaz, LA; Donehower, RC; Hidalgo, M; Laheru, DA; McManus, M; Messersmith, WA; Quackenbush, K; Rudek, MA; Taylor, GE; Wright, JJ; Zhao, M, 2013)	0.39
" PK analysis indicated a mean terminal half-life of 19."	( Safety, pharmacokinetics, and activity of EZN-2208, a novel conjugate of polyethylene glycol and SN38, in patients with advanced malignancies. Buchbinder, A; Chaudhary, I; Fu, S; Ghalib, MH; Goel, S; Hong, D; Kurzrock, R; Lokiec, F; Mani, S; Morgan-Linnell, SK; Mulcahy, M; Rezai, K; Urien, S; Wheler, J, 2012)	0.38
"To characterize the pharmacokinetic profile of elomotecan, a novel homocamptothecin analog, evaluate the dose-limiting toxicities, and establish the relationship between exposure and toxicity in the first Phase I study in patients with advanced malignant solid tumors."	( Population pharmacokinetic/pharmacodynamic modeling of drug-induced adverse effects of a novel homocamptothecin analog, elomotecan (BN80927), in a Phase I dose finding study in patients with advanced solid tumors. Cendrós, JM; Cvitkovic, F; Delavault, P; Lesimple, T; Obach, R; Peraire, C; Perez-Mayoral, A; Principe, P; Pruñonosa, J; Soto, E; Trocóniz, IF, 2012)	0.83
"The pharmacokinetic parameters and the toxicity pattern of elomotecan suggest that this novel homocamptothecin analog should be further explored in the clinical setting using a dose of 60 mg administered as a 30-min intravenous infusion, once every 3 weeks."	( Population pharmacokinetic/pharmacodynamic modeling of drug-induced adverse effects of a novel homocamptothecin analog, elomotecan (BN80927), in a Phase I dose finding study in patients with advanced solid tumors. Cendrós, JM; Cvitkovic, F; Delavault, P; Lesimple, T; Obach, R; Peraire, C; Perez-Mayoral, A; Principe, P; Pruñonosa, J; Soto, E; Trocóniz, IF, 2012)	0.81
" The drug concentration in plasma was determined and the pharmacokinetic behaviour was compared."	( [In vivo imaging in tumor-bearing animals and pharmacokinetics of PEGylated liposomes modified with RGD cyclopeptide]. Deng, LH; Tang, CY; Tu, LX; Wu, CB; Xu, YH, 2012)	0.38
"The purpose of this investigation was to evaluate the colon-targeted Irinotecan Hydrochloride (ITC-HCl) loaded microspheres by pharmacokinetic and biochemical studies."	( Colorectal cancer targeted Irinotecan-Assam Bora rice starch based microspheres: a mechanistic, pharmacokinetic and biochemical investigation. Ahmad, FJ; Ahmad, MZ; Akhter, S; Anwar, M; Kumar, A; Rahman, M; Talasaz, AH, 2013)	0.39
" There was no overlap in drug plasma levels observed from the bead and IV treatments when given 24 h apart and no difference between the pharmacokinetic profiles of the two cycles separated by 3 weeks."	( Feasibility, safety and pharmacokinetic study of hepatic administration of drug-eluting beads loaded with irinotecan (DEBIRI) followed by intravenous administration of irinotecan in a porcine model. Chung, ST; Czuczman, P; Finnie, J; Foster, D; Holden, RR; Kuchel, T; Lewis, AL; Porter, S, 2013)	0.39
" On the contrary, significant changes in the pharmacokinetic parameters of SN-38 were not observed."	( [Effect of tacrolimus on the pharmacokinetics and glucuronidation of SN-38, an active metabolite of irinotecan]. Fujioka, M; Hasegawa, T; Katoh, M; Nadai, M; Onishi, K; Sakakibara, Y; Tanaka, Y, 2013)	0.39
" Pharmacokinetic studies were also evaluated."	( UGT1A1 genotype-specific phase I and pharmacokinetic study for combination chemotherapy with irinotecan and cisplatin: a Saitama Tumor Board study. Furuya, K; Goto, T; Hirata, J; Horie, K; Kikuchi, Y; Kino, N; Kudoh, K; Takahashi, M; Takano, M; Yokota, H, 2013)	0.39
" Six of the eight pharmacodynamic parameters assume the same value as in the corresponding single drug models."	( A predictive pharmacokinetic-pharmacodynamic model of tumor growth kinetics in xenograft mice after administration of anticancer agents given in combination. Del Bene, F; Germani, M; Magni, P; Terranova, N, 2013)	0.39
" This hypothesis-generating study shows that EGFR ligands are significantly modulated by cetuximab plus irinotecan according to KRAS and BRAF mutational status, and they warrant further investigation as pharmacodynamic markers of resistance to anti-EGFRs."	( EGFR ligands as pharmacodynamic biomarkers in metastatic colorectal cancer patients treated with cetuximab and irinotecan. Antoniotti, C; Basolo, F; Bocci, G; Canu, B; Cremolini, C; Danesi, R; Di Desidero, T; Di Paolo, A; Falcone, A; Faviana, P; Fioravanti, A; Fontanini, G; Loupakis, F; Lupi, C; Masi, G; Orlandi, P; Salvatore, L; Schirripa, M; Sensi, E, 2014)	0.4
"A meta-analysis was conducted to evaluate the inter-patient pharmacokinetic (PK) variability of liposomal and small molecule (SM) anticancer agents."	( Meta-analysis of inter-patient pharmacokinetic variability of liposomal and non-liposomal anticancer agents. Caron, WP; Ramanathan, RK; Schell, RF; Sidone, BJ; Walsh, MD; White, TF; Zamboni, BA; Zamboni, WC, 2014)	0.4
"In this meta-analysis, the inter-patient pharmacokinetic variability of 9 liposomal and small molecule anti-cancer agents was studied."	( Meta-analysis of inter-patient pharmacokinetic variability of liposomal and non-liposomal anticancer agents. Caron, WP; Ramanathan, RK; Schell, RF; Sidone, BJ; Walsh, MD; White, TF; Zamboni, BA; Zamboni, WC, 2014)	0.4
" In the (TA)6/(TA)7 group, SN-38 peak concentration was correlated with CPT-11 starting dose and OS, valley concentration correlated with plasma bilirubin levels before CPT-11 treatment, delayed diarrhea, and OS."	( Analysis of UGT1A1*28 genotype and SN-38 pharmacokinetics for irinotecan-based chemotherapy in patients with advanced colorectal cancer: results from a multicenter, retrospective study in Shanghai. Cai, X; Cao, W; Ding, H; Liu, T; Wang, L; Wang, M; Xu, Q; Zhao, Z; Zhong, M; Zhou, X, 2013)	0.39
" For the (TA)6/(TA)6 genotype, CPT-11 dosage can be increased gradually to improve efficacy for patients with SN-38 peak concentration ≤43."	( Analysis of UGT1A1*28 genotype and SN-38 pharmacokinetics for irinotecan-based chemotherapy in patients with advanced colorectal cancer: results from a multicenter, retrospective study in Shanghai. Cai, X; Cao, W; Ding, H; Liu, T; Wang, L; Wang, M; Xu, Q; Zhao, Z; Zhong, M; Zhou, X, 2013)	0.39
"The safety, tolerability, and pharmacokinetic (PK) interactions of MK-0646 in combination with cetuximab and irinotecan were investigated in Japanese patients with advanced colorectal cancer."	( Phase 1 pharmacokinetic study of MK-0646 (dalotuzumab), an anti-insulin-like growth factor-1 receptor monoclonal antibody, in combination with cetuximab and irinotecan in Japanese patients with advanced colorectal cancer. Doi, T; Feng, HP; Fuse, N; Muro, K; Noguchi, K; Ohtsu, A; Shimamoto, T; Takahari, D; Ura, T; Yoshino, T, 2013)	0.39
"The pharmacokinetic biomodulation of irinotecan using oral ciclosporin does not improve the therapeutic index of irinotecan in advanced CRC."	( A randomised phase III trial of the pharmacokinetic biomodulation of irinotecan using oral ciclosporin in advanced colorectal cancer: results of the Panitumumab, Irinotecan & Ciclosporin in COLOrectal cancer therapy trial (PICCOLO). Blake, D; Bridgewater, J; Brown, S; Chau, I; Gollins, S; Gwyther, S; Hill, M; Lowe, C; Maisey, N; Marshall, H; Maughan, T; Middleton, G; Myint, S; Napp, V; Oliver, A; Richman, S; Seymour, M; Slater, S; Wadsley, J; Wagstaff, J, 2013)	0.39
" Correlations between pharmacokinetic data and incidence of neutropenia and diarrhea were also assessed."	( Pharmacokinetic assessment of irinotecan, SN-38, and SN-38-glucuronide: a substudy of the FIRIS study. Komatsu, Y; Muro, K; Sameshima, S; Satoh, T; Sugihara, K; Yamaguchi, K; Yasui, H, 2013)	0.39
"With the purpose to carry out the pharmacokinetic studies of 10-hydroxy camptothecin (10-HCPT) and hydroxyethyl starch (10-HCPT-HES) conjugate, an ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method has been developed and validated."	( Development and application of a UPLC-MS/MS method for the pharmacokinetic study of 10-hydroxy camptothecin and hydroxyethyl starch conjugate in rats. Cai, C; Li, G; Ren, T; Tang, X, 2014)	0.85
" ¹⁸FDG-PET may be a useful pharmacodynamic marker of SU5416 bioactivity but requires additional development."	( A phase I dose escalation and pharmacodynamic study of SU5416 (semaxanib) combined with weekly cisplatin and irinotecan in patients with advanced solid tumors. Bekaii-Saab, T; Clinton, SK; Grever, MR; Kraut, EH; Martin, LK; Monk, P; Serna, D, 2013)	0.39
" However, Oatp1a/1b-null mice had increased levels of carboxylesterase (Ces) enzymes, which caused higher conversion of irinotecan to SN-38 in plasma, potentially complicating pharmacokinetic analyses."	( OATP1A/1B transporters affect irinotecan and SN-38 pharmacokinetics and carboxylesterase expression in knockout and humanized transgenic mice. Elbatsh, A; Iusuf, D; Lin, F; Ludwig, M; Schinkel, AH; van de Steeg, E; van der Valk, M; van Esch, A; van Tellingen, O; Wagenaar, E, 2014)	0.4
" However, there is a paucity of data from sufficiently powered pharmacokinetic and pharmacodynamic studies to support dosage recommendations in such patients."	( Optimization of cancer chemotherapy on the basis of pharmacokinetics and pharmacodynamics: from patients enrolled in clinical trials to those in the 'real world'. Fujita, K; Sasaki, Y, 2014)	0.4
"The first-in-human phase 1 trial examined the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), pharmacokinetic profile, and antitumor activity of TLC388, a novel camptothecin with a unique lactone ring modification, in patients with advanced solid tumors."	( A phase 1 open-label, sequential dose-escalation study investigating the safety, tolerability, and pharmacokinetics of intravenous TLC388 administered to patients with advanced solid tumors. Cheng, AL; Cho, DC; Chuadhary, I; Coleman, T; Ghalib, MH; Ghamande, S; Goel, S; Hsu, SC; Kuo, MW; Kwak, EL; Lin, CC; Mach, WB; Shapiro, GI; Silverman, MH; Tseng, Y; Yang, JC, 2014)	0.6
" In rats, MXN-004 exhibited a longer half-life (sixfold) and much greater Vss as compared with irinotecan."	( In vitro cytotoxicity, pharmacokinetics and tissue distribution in rats of MXN-004, a novel conjugate of polyethylene glycol and SN38. Chen, X; He, Y; Li, C; Li, N; Qiu, Z; Ren, S; Tian, F; Wang, X; Zhang, Y; Zhao, D; Zhou, S, 2014)	0.4
" Alternatively, 5-FU doses can be adjusted based on 5-FU pharmacokinetic (PK) monitoring."	( Personalized dosing via pharmacokinetic monitoring of 5-fluorouracil might reduce toxicity in early- or late-stage colorectal cancer patients treated with infusional 5-fluorouracil-based chemotherapy regimens. Beachler, C; El-Deiry, WS; Harvey, HA; Kline, CL; Mackley, HB; McKenna, K; Messaris, E; Poritz, L; Schiccitano, A; Sheikh, H; Sivik, J; Staveley-O'Carroll, K; Stewart, D; Zhu, J, 2014)	0.4
"To facilitate new drug development, physiologically-based pharmacokinetic (PBPK) modeling methods receive growing attention as a tool to fully understand and predict complex pharmacokinetic phenomena."	( Estimation of feasible solution space using Cluster Newton Method: application to pharmacokinetic analysis of irinotecan with physiologically-based pharmacokinetic models. Konagaya, A; Kusuhara, H; Maeda, K; Yoshida, K, 2013)	0.39
" Possible causes in the irinotecan pharmacokinetic alterations were suggested, but they were not conclusive."	( Estimation of feasible solution space using Cluster Newton Method: application to pharmacokinetic analysis of irinotecan with physiologically-based pharmacokinetic models. Konagaya, A; Kusuhara, H; Maeda, K; Yoshida, K, 2013)	0.39
"The aim of this study was the evaluation of pharmacokinetic parameters, biomarkers, clinical outcome, and imaging parameters in metastatic colorectal cancer (mCRC) patients treated with FOLFIRI plus sunitinib."	( FOLFIRI and sunitinib as first-line treatment in metastatic colorectal cancer patients with liver metastases--a CESAR phase II study including pharmacokinetic, biomarker, and imaging data. Büchert, M; Burkholder, I; Jaehde, U; Kanefendt, F; Kuhlmann, J; Moritz, B; Mross, K; Scheulen, M; Sörgel, F; Strumberg, D, 2014)	0.4
"10-hydroxy camptothecin (10-HCPT) is an antitumor agent effective in the treatment of several solid tumors but its use is hampered by poor water solubility, low lactone stability, short plasma half-life and dose-limiting toxicity."	( Hydroxyethyl starch-10-hydroxy camptothecin conjugate: synthesis, pharmacokinetics, cytotoxicity and pharmacodynamics research. Cai, C; Li, G; Qi, Y; Tang, X, 2016)	1.11
"10-Hydroxy camptothecin (10-HCPT)-hydroxyethyl starch (HES) conjugates were prepared to improve the water solubility, prolong the half-life in plasma and increase the antitumor efficacy of 10-HCPT, and the structures of the conjugates were confirmed by NMR and infrared spectroscopy."	( Hydroxyethyl starch conjugates for improving the stability, pharmacokinetic behavior and antitumor activity of 10-hydroxy camptothecin. Cai, C; Li, G; Li, Y; Tang, X; Tang, Y; Xu, H; Yin, T; Zhang, Y, 2014)	1
" Pharmacokinetic results suggested that the overall systemic exposure to SN-38, the active metabolite of irinotecan, was affected by pazopanib to a greater extent than was the systemic exposure to irinotecan itself."	( A phase I open-label study of the safety, tolerability, and pharmacokinetics of pazopanib in combination with irinotecan and cetuximab for relapsed or refractory metastatic colorectal cancer. Bennouna, J; Botbyl, J; de Labareyre, C; Delord, JP; Deslandres, M; Ruiz-Soto, R; Senellart, H; Suttle, AB; Wixon, C, 2015)	0.42
"Sixteen of 19 patients were evaluable, with serial pharmacokinetic studies in ten patients."	( Phase I dose escalation and pharmacokinetic study of oral gefitinib and irinotecan in children with refractory solid tumors. Brennan, RC; Furman, W; Mao, S; McGregor, LM; Santana, V; Stewart, CF; Turner, DC; Wu, J, 2014)	0.4
" Pharmacokinetic analysis confirms that co-administration of gefitinib increases irinotecan bioavailability leading to an increased SN-38 lactone systemic exposure."	( Phase I dose escalation and pharmacokinetic study of oral gefitinib and irinotecan in children with refractory solid tumors. Brennan, RC; Furman, W; Mao, S; McGregor, LM; Santana, V; Stewart, CF; Turner, DC; Wu, J, 2014)	0.4
" Therapeutic drug monitoring is a valid tool to determine the pharmacokinetic of a drug and individualized drug therapy, adjusting patient's dose requirement through the measurement and interpretation of drug concentrations."	( [Clinical application, limits and perspectives of pharmacogenetic and pharmacokinetic analysis of anticancer drugs]. Chantry, AS; Ciccolini, J; Lacarelle, B; Quaranta, S, )	0.13
" Here, we describe an on-chip small intestine-liver coupled model for pharmacokinetic studies."	( An on-chip small intestine-liver model for pharmacokinetic studies. Fujii, T; Ikeda, T; Kimura, H; Nakayama, H; Sakai, Y, 2015)	0.42
" This study was initiated to build an integrated pharmacokinetic (PK) and pharmacodynamic (PD) population model of namitecan to guide future clinical development."	( Integrative population pharmacokinetic and pharmacodynamic dose finding approach of the new camptothecin compound namitecan (ST1968). Barbieri, P; Cresta, S; Delmonte, A; Fasolo, A; Gallerani, E; Gianni, L; Hess, D; Joerger, M; Pace, S; Sessa, C, 2015)	0.64
"15 l h(-1), with a long terminal half-life of 48 h."	( Integrative population pharmacokinetic and pharmacodynamic dose finding approach of the new camptothecin compound namitecan (ST1968). Barbieri, P; Cresta, S; Delmonte, A; Fasolo, A; Gallerani, E; Gianni, L; Hess, D; Joerger, M; Pace, S; Sessa, C, 2015)	0.64
" A wide inter-individual variability in irinotecan pharmacokinetic parameters and pharmacodynamics has been reported and associated to patients' genetic background."	( Development and validation of a high-performance liquid chromatography-tandem mass spectrometry method for the simultaneous determination of irinotecan and its main metabolites in human plasma and its application in a clinical pharmacokinetic study. Marangon, E; Mazzega, E; Posocco, B; Toffoli, G, 2015)	0.42
" Pharmacokinetic studies of the liposomal sum total CPT-11, released CPT-11, SN-38, SN-38G, 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]-carbonyloxycamptothecin, and 7-ethyl-10-[4-amino-1-piperidino]-carbonyloxycamptothecin in plasma were performed."	( Factors affecting the pharmacokinetics and pharmacodynamics of PEGylated liposomal irinotecan (IHL-305) in patients with advanced solid tumors. Bendell, JC; Burris, HA; Chan, E; Ikeda, S; Infante, JR; Jones, SF; Keedy, VL; Kirschbrown, WP; Kodaira, H; Lee, W; Rothenberg, ML; Wu, H; Zamboni, BA; Zamboni, WC, 2015)	0.61
"The population pharmacokinetic model reported here was developed using data from 2 phase 2 trials of irinotecan for treatment of malignant glioma to quantify the impact of concomitant therapy with enzyme-inducing antiepileptic drugs (EIAEDs) on irinotecan pharmacokinetics."	( Quantification of the impact of enzyme-inducing antiepileptic drugs on irinotecan pharmacokinetics and SN-38 exposure. Ames, MM; Berg, AK; Buckner, JC; Galanis, E; Jaeckle, KA; Reid, JM, 2015)	0.42
"This phase Ib study evaluated the pharmacokinetic profile and safety of ramucirumab, a recombinant human IgG1 neutralizing monoclonal antibody specific for vascular endothelial growth factor receptor 2, in combination with irinotecan, levofolinate and 5-fluorouracil (FOLFIRI) in Japanese patients with metastatic colorectal carcinoma (mCRC)."	( Safety and Pharmacokinetics of Second-line Ramucirumab plus FOLFIRI in Japanese Patients with Metastatic Colorectal Carcinoma. Gao, L; Gotoh, M; Nasroulah, F; Ohtsu, A; Yamazaki, K; Yoshino, T; Yoshizuka, N, 2015)	0.42
" Pharmacokinetic analyses were performed using WinNonLin and NONMEM."	( Phenotyping of UGT1A1 Activity Using Raltegravir Predicts Pharmacokinetics and Toxicity of Irinotecan in FOLFIRI. Cheong, PF; Fan, L; Goh, BC; Hee, KH; Lee, LS; Lee, SC; Sapari, NS; Seng, KY; Soh, TI; Soo, R; Soong, R; Wang, LZ; Wong, A; Yong, WP, 2016)	0.43
"10-Hydroxy camptothecin (10-HCPT) is an antitumor agent effective in the treatment of several solid tumors but its use is hampered by poor water solubility, low lactone stability, short plasma half-life and dose-limiting toxicity."	( Well-defined hydroxyethyl starch-10-hydroxy camptothecin super macromolecule conjugate: cytotoxicity, pharmacodynamics research, tissue distribution test and intravenous injection safety assessment. Li, G; Zhao, L; Zhao, M, 2016)	1.09
"The objective of this research is to develop and validate a sensitive and reproducible UPLC-MS/MS method to quantify irinotecan, its active metabolite SN-38 and SN-38 glucuronide (phase II metabolite of SN-38) simultaneously in different bio-matrices (plasma, urine, feces), tissues (liver and kidney) and to use the method to investigate its pharmacokinetic behavior in rats."	( Development and validation of an UPLC-MS/MS method for the quantification of irinotecan, SN-38 and SN-38 glucuronide in plasma, urine, feces, liver and kidney: Application to a pharmacokinetic study of irinotecan in rats. Basu, S; Gao, S; Hu, M; Yin, T; Zeng, M, 2016)	0.43
"In a cohort of 109 metastatic colorectal cancer patients treated with irinotecan (180 mg/m(2)) in combination with other drugs, associations were assessed between 21 selected single nucleotide polymorphisms of NR1I2 or NR1I3 and pharmacokinetic parameters or toxicity of irinotecan and its metabolites."	( Effect of Single Nucleotide Polymorphisms in the Xenobiotic-sensing Receptors NR1I2 and NR1I3 on the Pharmacokinetics and Toxicity of Irinotecan in Colorectal Cancer Patients. Boyer, JC; Del Rio, M; Evrard, A; Gassiot, M; Mbatchi, LC; Robert, J; Thomas, F; Tubiana, N; Ychou, M, 2016)	0.43
" The pharmacokinetic study in rats of these nanoparticles with borneol was carried out."	( Effects of borneol on the pharmacokinetics of 9-nitrocamptothecin encapsulated in PLGA nanoparticles with different size via oral administration. Han, L; Li, R; Qing, J; Qiu, M; Ru, G; Sheng, J; Wang, J, 2016)	0.68
" Unfortunately, such preclinical and clinical pharmacokinetic studies are rare."	( Pharmacokinetics of metronomic chemotherapy: a neglected but crucial aspect. Bocci, G; Kerbel, RS, 2016)	0.43
" This drug is a feasible candidate for therapeutic drug monitoring due to the presence of a wide inter-individual variability in the pharmacokinetic and pharmacodynamic parameters."	( Cross-validation of a mass spectrometric-based method for the therapeutic drug monitoring of irinotecan: implementation of matrix-assisted laser desorption/ionization mass spectrometry in pharmacokinetic measurements. Agostini, M; Calandra, E; Crotti, S; Giodini, L; Marangon, E; Nitti, D; Posocco, B; Toffoli, G; Traldi, P, 2016)	0.43
"The objective of this phase II study was to evaluate the potential of pharmacokinetic (PK) drug-drug interactions between ramucirumab and irinotecan or its metabolite, SN-38, when administered with folinic acid and 5-fluorouracil (FOLFIRI)."	( Lack of pharmacokinetic drug-drug interaction between ramucirumab and irinotecan in patients with advanced solid tumors. Asakiewicz, C; Braiteh, F; Chaudhary, A; Denlinger, CS; Gao, L; Lee, JJ; Lin, Y; LoRusso, P; Nasroulah, F; Shepard, DR; Wang, D, 2016)	0.43
"Circulating tumor cells (CTCs), which are captured from blood with anti-epithelial cell adhesion molecule (EpCAM) antibodies, have established prognostic value in specific epithelial cancers, but less is known about their utility for assessing patient response to molecularly targeted agents via measurement of pharmacodynamic (PD) endpoints."	( Promise and limits of the CellSearch platform for evaluating pharmacodynamics in circulating tumor cells. Balasubramanian, P; Chen, AP; Evrard, YA; Kinders, RJ; Kummar, S; Wang, L, 2016)	0.43
" Here, the pharmacokinetic interactions in mice between irinotecan, its active metabolite SN-38 and MBL-II-141 were characterized quantitatively in the blood and in the brain."	( Pharmacokinetic interactions in mice between irinotecan and MBL-II-141, an ABCG2 inhibitor. Di Pietro, A; Guitton, J; Hénin, E; Honorat, M; Payen, L; Tod, M, 2017)	0.46
"These results may help to anticipate the pharmacokinetic interactions between MBL-II-141 and other ABCG2 substrates."	( Pharmacokinetic interactions in mice between irinotecan and MBL-II-141, an ABCG2 inhibitor. Di Pietro, A; Guitton, J; Hénin, E; Honorat, M; Payen, L; Tod, M, 2017)	0.46
"This method was successfully used to quantify CPT-11, SN-38, and SN-38G and applied to a pharmacokinetic study."	( Determination of irinotecan, SN-38 and SN-38 glucuronide using HPLC/MS/MS: Application in a clinical pharmacokinetic and personalized medicine in colorectal cancer patients. Atasilp, C; Chansriwong, P; Prommas, S; Puangpetch, A; Rerkarmnuaychoke, B; Reungwetwattana, T; Sirachainan, E; Sirilerttrakul, S; Sukasem, C; Wongwaisayawan, S, 2018)	0.48
"To establish a physiologically-based pharmacokinetic (PBPK) model for analyzing the factors associated with side effects of irinotecan by using a computer-based virtual clinical study (VCS) because many controversial associations between various genetic polymorphisms and side effects of irinotecan have been reported."	( Virtual Clinical Studies to Examine the Probability Distribution of the AUC at Target Tissues Using Physiologically-Based Pharmacokinetic Modeling: Application to Analyses of the Effect of Genetic Polymorphism of Enzymes and Transporters on Irinotecan Ind Hosokawa, M; Sugiyama, Y; Tomaru, A; Toshimoto, K, 2017)	0.46
" IMMU-132 cleared with a half-life of approximately 11 to 14 hours, reflecting the release of SN-38 from the conjugate; IgG cleared more slowly (half-life, approximately 103-114 hours)."	( Sacituzumab govitecan (IMMU-132), an anti-Trop-2-SN-38 antibody-drug conjugate for the treatment of diverse epithelial cancers: Safety and pharmacokinetics. Bardia, A; Goldenberg, DM; Govindan, SV; Guarino, M; Isakoff, SJ; Maliakal, P; Mayer, IA; Messersmith, WA; Ocean, AJ; Picozzi, VJ; Sharkey, RM; Starodub, AN; Vahdat, LT; Wegener, WA, 2017)	0.46
"Sacituzumab govitecan has a predictable pharmacokinetic profile and manageable toxicity at doses of 8 and 10 mg/kg."	( Sacituzumab govitecan (IMMU-132), an anti-Trop-2-SN-38 antibody-drug conjugate for the treatment of diverse epithelial cancers: Safety and pharmacokinetics. Bardia, A; Goldenberg, DM; Govindan, SV; Guarino, M; Isakoff, SJ; Maliakal, P; Mayer, IA; Messersmith, WA; Ocean, AJ; Picozzi, VJ; Sharkey, RM; Starodub, AN; Vahdat, LT; Wegener, WA, 2017)	0.46
" Mainly metabolized by hepatic route, and excreted through biliary tract, this dug has been found to possess high variation in patients in its pharmacokinetic (PK) profile."	( Physiologically based pharmacokinetic modeling for predicting irinotecan exposure in human body. Ahmad, T; Ahmed, M; Czejka, M; Fan, Y; Khan, RA; Mansoor, N; Sharib, S; Yang, DH, 2017)	0.46
" Methods for understanding PK will help in conducting pharmacokinetic - pharmacodynamic (PK-PD) correlations and improving the quality and applicability of data obtained using zebrafish."	( Correlation of pharmacokinetics and brain penetration data of adult zebrafish with higher mammals including humans. Kulkarni, P; Medishetti, R; Nune, N; Oruganti, S; Rao, P; Saxena, U; Sripuram, V; Sriram, D; Yellanki, S; Yogeeswari, P, )	0.13
" The objective of this study was to develop a population pharmacokinetic (popPK) model of EP and four of its metabolites (irinotecan, SN38, SN38-glucuronide, and APC) and determine covariates affecting their pharmacokinetics."	( Integrated population pharmacokinetics of etirinotecan pegol and its four metabolites in cancer patients with solid tumors. Chia, YL; Eldon, MA; Gordi, T; Hoch, U; Sy, SKB, 2018)	0.48
"CZ48, a prodrug of camptothecin (CPT), has a broad spectrum of antitumor activity against various types of human tumors without severe toxicity in preclinical human tumor-xenografted mouse models, which facilitates further preclinical and clinical pharmacokinetic (PK) evaluations of CZ48."	( Ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) assay for simultaneous quantifications of CZ48, lactone-stabilized camptothecin, and camptothecin and their pharmacokinetic and biliary evaluations in rats. Chow, DS; Kim, YJ; Tu, Y, 2018)	1.01
" Here, we examined the pharmacokinetic (PK) profiles of DS-8201a and DXd in cynomolgus monkeys, a cross-reactive species."	( Comprehensive preclinical pharmacokinetic evaluations of trastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody-drug conjugate, in cynomolgus monkeys. Ando, O; Nagai, Y; Oitate, M; Shiozawa, H, 2019)	0.51
" The individualized dosing of CPT-11 is essential to ensure optimal pharmacotherapy in cancer patients, given the wide interindividual pharmacokinetic variability of this drug and its active metabolite SN-38."	( Population pharmacokinetic model of irinotecan and its metabolites in patients with metastatic colorectal cancer. Aldaz, A; Insausti, A; Oyaga-Iriarte, E; Sayar, O, 2019)	0.51
" Besides, in vivo pharmacokinetic studies further revealed that the availability of both CZ48 and its metabolite CPT were obviously enhanced after the incorporation of CZ48 into PLA microbubbles."	( Optimal construction and pharmacokinetic study of CZ48-loaded poly (lactic acid) microbubbles for controlled drug delivery. Guo, SL; Li, SY, 2019)	0.51
" Supported by several demographic data, blood markers and pharmacokinetic parameters resulting from a non-compartmental pharmacokinetic study of CPT-11 and its metabolites (SN-38 and SN-38-G), we use machine learning techniques to predict high degrees of different toxicities (leukopenia, neutropenia and diarrhea) in new patients."	( Prediction of irinotecan toxicity in metastatic colorectal cancer patients based on machine learning models with pharmacokinetic parameters. Aldaz, A; Insausti, A; Oyaga-Iriarte, E; Sayar, O, 2019)	0.51
" Pharmacokinetic (PK) studies were conducted in mice and the SBE-β-CD based formulation was compared with the Cremophor EL formulation."	( Pharmacokinetic modeling of the blood-stable camptothecin analog AR-67 in two different formulations. Adane, E; Leggas, M; Liu, X; Tang, F, 2019)	0.77
" In the current study, we aimed to investigate whether the synergistic effect is related to a potential pharmacokinetic interaction between sunitinib and irinotecan."	( The pharmacokinetic interaction between irinotecan and sunitinib. Jiang, L; Liu, Y; Luan, X; Wang, L; Wang, S; Wang, X; Wang, Z; Xia, Y; Zhang, Z, 2020)	0.56
" According to the pharmacokinetic parameters of mean residence time, half-life period and clearance rate, the 10-hydroxycamptothecin-tetrandrine liposome complexes prolongs the retention and circulation time of 10-hydroxycamptothecin in vivo, achieving a good sustained release effect."	( Pharmacokinetics of 10-hydroxycamptothecin-tetrandrine liposome complexes in rat by a simple and sensitive ultra-high performance liquid chromatography with tandem mass spectrometry. Mao, J; Ping, Y; Shuang, R; Wang, M; Zou, J, 2020)	1.05
" Using pharmacokinetic analysis, it is possible to directly evaluate enzyme activity and consider what kind of enzyme variation causes the increase in the AUC of SN-38."	( Effect of UGT1A1, CYP3A and CES Activities on the Pharmacokinetics of Irinotecan and its Metabolites in Patients with UGT1A1 Gene Polymorphisms. Ayukawa, H; Endo, S; Furuse, J; Furuta, T; Hirano, R; Kaneko, S; Kawai, K; Kobayashi, T; Minowa, Y; Nagashima, F; Naruge, D; Okano, N; Shibasaki, H; Yokokawa, A, 2021)	0.62
"The aim of the present study was to characterize the pharmacokinetics of irinotecan and its four main metabolites (SN-38, SN-38G, APC and NPC) in metastatic colorectal cancer patients treated with FOLFIRI and FOLFIRINOX regimens and to quantify and explain the inter-individual pharmacokinetic variability in this context."	( Population pharmacokinetic model of irinotecan and its four main metabolites in patients treated with FOLFIRI or FOLFIRINOX regimen. Barbolosi, D; Deyme, L; Evrard, A; Gattacceca, F; Mbatchi, LC; Tubiana-Mathieu, N; Ychou, M, 2021)	0.62
" First, fixed and random effects models were selected using statistical and graphical methods; second, the impact of covariates on pharmacokinetic parameters was evaluated to explain the inter-individual variability in pharmacokinetic parameters."	( Population pharmacokinetic model of irinotecan and its four main metabolites in patients treated with FOLFIRI or FOLFIRINOX regimen. Barbolosi, D; Deyme, L; Evrard, A; Gattacceca, F; Mbatchi, LC; Tubiana-Mathieu, N; Ychou, M, 2021)	0.62
" Moreover, a direct conversion of NPC into SN-38 had never been described before in a population pharmacokinetic model of irinotecan."	( Population pharmacokinetic model of irinotecan and its four main metabolites in patients treated with FOLFIRI or FOLFIRINOX regimen. Barbolosi, D; Deyme, L; Evrard, A; Gattacceca, F; Mbatchi, LC; Tubiana-Mathieu, N; Ychou, M, 2021)	0.62
" In current study, we established a new physiologically based pharmacokinetic (PBPK) model to predict the disposition kinetics of irinotecan."	( Development of a physiologically based pharmacokinetic model to predict irinotecan disposition during inflammation. Chityala, PK; Ghose, R; Li, L; Lin, Z; Tao, G, 2022)	0.72

Compound-Compound Interactions

The purpose of this study was to determine the maximum-tolerated dose and the dose-limiting toxicities of CPT-11. Two different anticancer drugs, camptothecin and chlorambucil, are successfully connected together by a disulfide linkage to get a novel drug-drug conjugated prodrug (G)

Excerpt	Reference	Relevance
"The purpose of this study was to determine the maximum-tolerated dose and the dose-limiting toxicities of CPT-11, a new derivative of camptothecin, in combination with a fixed dose of cisplatin in patients with non-small-cell lung cancer (NSCLC)."	( CPT-11 in combination with cisplatin for advanced non-small-cell lung cancer. Fukuoka, M; Kishimoto, S; Kudoh, S; Kusunoki, Y; Masuda, N; Matsui, K; Nakagawa, K; Negoro, S; Takada, M; Takifuji, N, 1992)	0.49
" The initial dose of CPT-11 was 30 mg/m2 given as a 90-minute intravenous (IV) infusion on days 1, 8, and 15 in combination with cisplatin (80 mg/m2 IV on day 1) given every 4 weeks."	( CPT-11 in combination with cisplatin for advanced non-small-cell lung cancer. Fukuoka, M; Kishimoto, S; Kudoh, S; Kusunoki, Y; Masuda, N; Matsui, K; Nakagawa, K; Negoro, S; Takada, M; Takifuji, N, 1992)	0.28
" In an attempt to establish whether the combination of CPT-11 with other standard anti-cancer agents would be of any benefit, we studied the effects of CPT-11 in combination with 11 other anti-cancer agents on a human T-cell leukemia cell line, MOLT-3, in culture."	( Effects of CPT-11 in combination with other anti-cancer agents in culture. Akutsu, M; Inoue, Y; Kano, Y; Miura, Y; Sakamoto, S; Suda, K; Suzuki, K; Yoshida, M, 1992)	0.28
"To investigate the effects of CPT-11 in combination with other anticancer agents, a human Burkitt's lymphoma cell line, Dauji, was incubated for 3 days in the presence of SN-38 (active substance of CPT-11) and the combined drug and cell growth inhibition was determined by MTT assay."	( [Effects of SN-38 in combination with other anticancer agents against Dauji cells]. Akutsu, M; Kano, Y; Miura, Y; Suzuki, K; Tsunoda, S, 1994)	0.29
" The first phase I trial of CPT-11 combined with cisplatin achieved an encouraging response rate of 54% in 27 patients with previously untreated NSCLC, and the recommended schedule for phase II studies was 60 mg/m2 of CPT-11 (days 1, 8, and 15) plus 80 mg/m2 of cisplatin (day 1) given at 4-week intervals."	( Clinical studies of irinotecan alone and in combination with cisplatin. Fukuoka, M; Masuda, N, 1994)	0.29
" Two combination phase I trials were undertaken to determine the maximum tolerated dose of CPT-11 in combination with cisplatin and vindesine in patients with advanced non-small cell lung cancer."	( Phase I clinical trial of irinotecan (CPT-11), 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothecin, and cisplatin in combination with fixed dose of vindesine in advanced non-small cell lung cancer. Arioka, H; Eguchi, K; Karato, A; Kunikane, H; Nishio, M; Ohe, Y; Oshita, F; Sasaki, Y; Shinkai, T; Tamura, T, 1994)	0.5
"Transcatheter arterial embolization (TAE) using hydroxycamptothecin, cantharidin and cisplatin which were mixed thoroughly with lipiodol, combined with large doses interferon and interleukin-2 as adoptive immunotherapy were carried out in the treatment of 48 patients with unresectable advanced stage primary hepatoma, evaluation of therapeutic effect showed that partial remission rate was 54."	( [Chinese material medica combined with cisplatin and lipiodol through transcatheter arterial embolization in the treatment of primary hepatoma]. Yu, ZJ, 1993)	0.53
"The cytotoxic effects of various antimetabolites (fluorouracil, methotrexate, or cytarabine), antimicrotubule agents (vincristine or paclitaxel [Taxol]), DNA alkylating agents (melphalan, bis[chloroethyl]nitrosourea [BCNU], or 4-hydroperoxycyclophosphamide [4HC]), and a DNA-platinating agent (cisplatin), alone and in combination with TPT, were measured in clonogenic (i."	( Cytotoxic effects of topotecan combined with various anticancer agents in human cancer cell lines. Buckwalter, CA; Donehower, RC; Grochow, LB; Kaufmann, SH; Peereboom, D; Rowinsky, EK; Svingen, PA, 1996)	0.29
"TPT cytotoxicity appears to be enhanced more by combination with certain DNA-damaging agents than by combination with antimetabolites or antimicrotubule agents."	( Cytotoxic effects of topotecan combined with various anticancer agents in human cancer cell lines. Buckwalter, CA; Donehower, RC; Grochow, LB; Kaufmann, SH; Peereboom, D; Rowinsky, EK; Svingen, PA, 1996)	0.29
" The in vivo antitumor activity of 131I-NCC-CO-411 monoclonal antibody against carcinoembryonic antigen in combination with CAM was assessed by a tumor growth rate in LS 174T tumor-bearing nude mice."	( Enhancement of the antitumor effect of gamma-ray irradiation in combination with camptothecin against human colorectal adenocarcinoma. Kojima, S; Oyamada, H; Ueno, Y; Wang, DS, 1996)	0.52
"Based on preclinical data that demonstrated synergy between alkylating agents and topoisomerase (topo) I poisons, we determined the maximum-tolerated dose (MTD) of topotecan, using a 5 day bolus schedule, that could be given in combination with a single, fixed dose of cyclophosphamide."	( Dose-escalation and pharmacodynamic study of topotecan in combination with cyclophosphamide in patients with refractory cancer. Anderson, S; Beidler, D; Belliveau, D; Burtness, BA; Cheng, YC; Fedele, J; Flynn, SD; Murren, JR; Pizzorno, G; Tocino, I; Zelterman, D, 1997)	0.3
"0 mg/ m2/d if it is administered with G-CSF."	( Dose-escalation and pharmacodynamic study of topotecan in combination with cyclophosphamide in patients with refractory cancer. Anderson, S; Beidler, D; Belliveau, D; Burtness, BA; Cheng, YC; Fedele, J; Flynn, SD; Murren, JR; Pizzorno, G; Tocino, I; Zelterman, D, 1997)	0.3
"A dose-escalation study of irinotecan hydrochloride (CPT-11) combined with fixed-dose cisplatin was conducted to determine the maximum-tolerated dose (MTD), dose-limiting toxicities, and objective response rate in patients with advanced gastric cancer."	( Phase I-II study of irinotecan hydrochloride combined with cisplatin in patients with advanced gastric cancer. Boku, N; Fujii, T; Fukuda, H; Kondo, H; Muro, K; Oda, Y; Ohtsu, A; Oka, M; Ono, H; Saito, D; Shimada, Y; Shirao, K; Watanabe, Y; Yamao, T; Yokoyama, T; Yoshida, S, 1997)	0.3
"To determine the optimal combination of commonly used anticancer agents with 7-ethyl-10-hydroxy-camptothecin (SN-38), an active metabolite of 7-ethyl-10-[4(1-piperidino)-1-piperidino] carbonyloxy camptothecin (CPT-11), for chemotherapy of lung cancer, we studied the effects of SN-38 in combination with six representative anticancer agents on the human small cell lung cancer (SCLC) cell line, NCl N417, and the non-small cell lung cancer (NSCLC) cell line, PC-9."	( Effect of CPT-11 in combination with other anticancer agents in lung cancer cells. Bai, F; Hara, N; Kawasaki, M; Mizuno, K; Nakanishi, Y; Pei, XH; Takayama, K; Tsuruta, N, 1997)	0.52
" We conducted a phase II study of CPT-11 combined with cisplatin to evaluate the efficacy and toxicity of this regimen in patients with previously untreated SCLC."	( Phase II study of irinotecan combined with cisplatin in patients with previously untreated small-cell lung cancer. West Japan Lung Cancer Group. Ariyoshi, Y; Fujiwara, Y; Fukuoka, M; Furuse, K; Kinoshita, A; Kudoh, S; Takada, Y; Yamamoto, H, 1998)	0.3
" CPT-11 60 mg/m2 was administered intravenously on days 1, 8, and 15 in combination with cisplatin 60 mg/m2 on day 1 every 28 days."	( Phase II study of irinotecan combined with cisplatin in patients with previously untreated small-cell lung cancer. West Japan Lung Cancer Group. Ariyoshi, Y; Fujiwara, Y; Fukuoka, M; Furuse, K; Kinoshita, A; Kudoh, S; Takada, Y; Yamamoto, H, 1998)	0.3
"CPT-11 (60 mg/m2 on days 1, 8 and 15) in combination with CDDP (80 mg/m2 on day 1) has shown promising antitumor activity for non-small-cell lung cancer (NSCLC), but dose-limiting toxicities (DLT) are leukopenia and diarrhea, with a wide variation among patients."	( Irinotecan (CPT-11) in combination with weekly administration of cisplatin (CDDP) for non-small-cell lung cancer. Hibino, S; Hino, M; Kabe, J; Kamimura, M; Kobayashi, K; Kudo, K; Kudoh, S; Shibuya, M; Shinbara, A; Takeda, Y, 1998)	0.3
"The value of weekly administration of CDDP in combination with CPT-11 was shown by (1) diarrhea not being dose-limiting, (2) mild nausea, (3) well-maintained AUC of free platinum, and (4) promising activity."	( Irinotecan (CPT-11) in combination with weekly administration of cisplatin (CDDP) for non-small-cell lung cancer. Hibino, S; Hino, M; Kabe, J; Kamimura, M; Kobayashi, K; Kudo, K; Kudoh, S; Shibuya, M; Shinbara, A; Takeda, Y, 1998)	0.3
"The efficacy and safety of irinotecan (CPT-11) combined with cisplatin (CDDP) were assessed in 24 previously untreated patients with primary non-small cell lung cancer."	( [Clinical evaluation of irinotecan combined with cisplatin by divided administration in patients with untreated primary non-small cell lung cancer]. Asano, T; Kawaji, K; Kobayashi, M; Mukai, J; Namikawa, O; Sano, T; Yamamoto, A, 1998)	0.3
" In this study, the potential application of MGI-114 in the treatment of colon cancer was further explored by evaluating the activity of MGI-114 in combination with irinotecan (CPT-11) and 5-fluorouracil (5FU)."	( Enhanced antitumor activity of 6-hydroxymethylacylfulvene in combination with irinotecan and 5-fluorouracil in the HT29 human colon tumor xenograft model. Britten, CD; Eckhardt, SG; Hilsenbeck, SG; MacDonald, JR; Mangold, G; Marty, J; Rowinsky, EK; Von Hoff, DD; Weitman, S, 1999)	0.3
"To determine the maximum-tolerated dose (MTD) and recommended dose of irinotecan (CPT-11) in combination with fluorouracil (5-FU) and leucovorin (LV), using a biweekly LV5FU2 regimen and increasing doses of CPT-11, and to assess the efficacy of this combination in pretreated patients with colorectal cancer (CRC)."	( Irinotecan combined with bolus fluorouracil, continuous infusion fluorouracil, and high-dose leucovorin every two weeks (LV5FU2 regimen): a clinical dose-finding and pharmacokinetic study in patients with pretreated metastatic colorectal cancer. Armand, JP; Bexon, A; Bonnay, M; Ducreux, M; Mahjoubi, M; Méry-Mignard, D; Rougier, P; Seitz, JF; Ychou, M, 1999)	0.3
" CPT-11 at 180 to 200 mg/m(2) in combination with LV5FU2 has been selected as the recommended dose for further studies."	( Irinotecan combined with bolus fluorouracil, continuous infusion fluorouracil, and high-dose leucovorin every two weeks (LV5FU2 regimen): a clinical dose-finding and pharmacokinetic study in patients with pretreated metastatic colorectal cancer. Armand, JP; Bexon, A; Bonnay, M; Ducreux, M; Mahjoubi, M; Méry-Mignard, D; Rougier, P; Seitz, JF; Ychou, M, 1999)	0.3
"For phase II studies, we recommend irinotecan 260 mg/m(2) combined with cisplatin 80 mg/m(2) once every 3 weeks for chemotherapy-naive patients in good physical condition, and irinotecan 200 mg/m(2) combined with cisplatin 80 mg/m(2) for other patients."	( Phase I study of 3-week schedule of irinotecan combined with cisplatin in patients with advanced solid tumors. de Boer-Dennert, MM; de Jonge, MJ; Jacques, C; Planting, AS; Sparreboom, A; ter Steeg, J; van der Burg, ME; Verweij, J, 2000)	0.31
" We conducted a Phase I study of CPT-11 combined with carboplatin in previously untreated solid cancers, especially advanced lung cancer."	( Phase I study of irinotecan combined with carboplatin in previously untreated solid cancers. Fukuda, M; Kawabata, S; Kinoshita, A; Kohno, S; Nakatomi, K; Noguchi, Y; Oka, M; Soda, H; Takatani, H; Terashi, K; Tsukamoto, K; Tsurutani, J, 1999)	0.3
" In order to promote the clinical response of chemotherapy for colorectal cancer using CPT-11, one of the most effective strategies is to use it in combination with other anticancer agents."	( In vitro augmentation of antitumor effect in combination with CPT-11 and CDDP for human colorectal cancer. Hotta, T; Ishimoto, K; Iwahashi, M; Matsuda, K; Tanaka, H; Tani, M; Tanimura, H; Tsunoda, T; Yamaue, H, 2000)	0.31
" The augmentation of the antitumor effectiveness of 7-ethyl-10-hydroxy-CPT (SN-38) was analyzed in combination with other anticancer agents."	( In vitro augmentation of antitumor effect in combination with CPT-11 and CDDP for human colorectal cancer. Hotta, T; Ishimoto, K; Iwahashi, M; Matsuda, K; Tanaka, H; Tani, M; Tanimura, H; Tsunoda, T; Yamaue, H, 2000)	0.31
"The percent inhibition of SN-38 in combination with cisplatin (CDDP) and mitomycin revealed a high anticancer effect compared with each anticancer agent alone for freshly isolated rectal cancer."	( In vitro augmentation of antitumor effect in combination with CPT-11 and CDDP for human colorectal cancer. Hotta, T; Ishimoto, K; Iwahashi, M; Matsuda, K; Tanaka, H; Tani, M; Tanimura, H; Tsunoda, T; Yamaue, H, 2000)	0.31
"Based upon the results of phase I study of irinotecan (CPT-11) combined with cisplatin (CDDP) on non-small cell lung cancer (NSCLC), a combination phase II study on NSCLC was carried out from Feb."	( [A phase II study of irinotecan combined with cisplatin in non-small cell lung cancer. CPT-11 Lung Cancer Study Group]. Fujita, A; Fukuoka, M; Katakami, N; Kurita, Y; Nagao, K; Nakano, M; Negoro, S; Niitani, H; Saito, R, 2000)	0.31
"Irinotecan combined with fluorouracil and calcium folinate was well-tolerated and increased response rate, time to progression, and survival, with a later deterioration in quality of life."	( Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial. Alakl, M; Awad, L; Carmichael, J; Cunningham, D; Douillard, JY; Gruia, G; Iveson, T; James, RD; Jandik, P; Karasek, P; Navarro, M; Roth, AD; Rougier, P, 2000)	0.31
"The results revealed synergistic cytotoxicity when vinflunine was combined with cisplatin, mitomycin C, doxorubicin or 5-fluorouracil."	( In vitro synergistic effects of vinflunine, a novel fluorinated vinca alkaloid, in combination with other anticancer drugs. Barret, JM; Etiévant, C; Hill, BT, 2000)	0.31
"Based on preclinical data demonstrating synergy between camptothecin analogues and taxanes, we determined the maximum tolerated dose (MTD) of irinotecan that could be given in combination with a fixed dose of paclitaxel of 75 mg/m2, when both drugs were delivered on a weekly schedule."	( Dose escalation and pharmacokinetic study of irinotecan in combination with paclitaxel in patients with advanced cancer. Burtness, BA; Cheng, Y; DiStasio, SA; Leffert, JJ; Li, X; McKeon, A; Murren, JR; Peccerillo, K; Pizzorno, G, 2000)	0.55
"The activity of temozolomide combined with irinotecan (CPT-11) was evaluated against eight independent xenografts (four neuroblastomas, three rhabdomyosarcomas, and one glioblastoma)."	( Antitumor activity of temozolomide combined with irinotecan is partly independent of O6-methylguanine-DNA methyltransferase and mismatch repair phenotypes in xenograft models. Brent, TP; Cheshire, PJ; Friedman, HS; Houghton, PJ; Kirstein, MN; Poquette, CA; Richmond, LB; Stewart, CF; Tan, M, 2000)	0.31
"To determine the dose-limiting toxicity of CPT-11 in combination with oxaliplatin, and the maximal tolerated dose (MTD) and the recommended dose (RD) of CPT-11 using an every two weeks schedule."	( Dose escalation of CPT-11 in combination with oxaliplatin using an every two weeks schedule: a phase I study in advanced gastrointestinal cancer patients. Cvitkovic, E; Di Palma, M; Goldwasser, F; Gross-Goupil, M; Marceau-Suissa, J; Misset, JL; Tigaud, JM; Wasserman, E; Yovine, A, 2000)	0.31
" On the basis of these studies, our group has begun to evaluate effects of RFS2000 (9-nitro-20(S)-camptothecin) (9-NC) in combination with a series of other antitumor agents."	( In vitro antitumor activity of 9-nitro-camptothecin as a single agent and in combination with other antitumor drugs. Bernacki, RJ; Brun, Y; Gambacorta, P; Greco, WR; Pera, P, 2000)	0.79
" The prevention of CPT-11-induced side effects by oral alkalization (OA) combined with control of defecation (CD) was estimated in a case-control study of lung cancer patients."	( Prevention of irinotecan (CPT-11)-induced diarrhea by oral alkalization combined with control of defecation in cancer patients. Akiyama, Y; Handa, S; Kobayashi, K; Kudo, K; Kudoh, S; Soma, T; Takeda, Y, 2001)	0.31
" Four cohorts of patients were recruited with MMC given at 8 mg/m2 for the first 3 levels together with irinotecan at 300 mg/m2, 325 mg/m2, and 350 mg/m2; the fourth dose level was given with MMC at 10 mg/m2 and irinotecan at 325 mg/m2."	( Phase I-II study of irinotecan in combination with mitomycin C in patients with advanced gastrointestinal cancer. Adam, R; Antoine, EC; Bassot, V; Benhammonda, A; Bismuth, H; Castaing, D; Gil-Delgado, MA; Grapin, JP; Guinet, F; Khayat, D, 2001)	0.31
" Preclinical and phase I trials have shown the additive or synergistic activity of temozolomide combined with carmustine against solid tumors, including malignant glioma, and the sequence-dependent effects of the combination."	( Temozolomide in combination with other cytotoxic agents. Prados, M, 2001)	0.31
"From December 1994 to July 1997, we conducted a dose escalation study of irinotecan combined with carboplatin in 17 patients with advanced non-small-cell lung cancer (NSCLC) to determine the maximum tolerated dose and the dose-limiting toxicities."	( Dose escalation study of irinotecan combined with carboplatin for advanced non-small-cell lung cancer. Fukuoka, M; Negoro, S; Nitta, T; Takeda, K; Takifuji, N; Terakawa, K; Yoshimura, N, 2001)	0.31
") UFT (250 mg/m(2)/day) for 21 days of a 28-day cycle combined with increasing intravenous (i."	( Phase I trial of weekly irinotecan combined with UFT as second-line treatment for advanced colorectal cancer. Alonso, V; Antón, A; Escudero, P; Herrero, A; Isla, MD; Martinez-Trufero, J; Mayordomo, JI; Sáenz, A; Tres, A; Zorrilla, M, 2001)	0.31
"Fifteen patients with isolated liver metastases of colorectal carcinoma were treated with regional administration of CPT-11 in combination with 5-fluorouracil/folinic acid (5-FU/FA)."	( Regional administration of irinotecan in combination with 5-fluorouracil and leucovorin in patients with colorectal cancer liver metastases--a pilot experience. Dvorák, J; Jandík, P; Malírová, E; Megancová, J; Melichar, B; Tousková, M; Voboril, Z, )	0.13
" A phase II study was conducted to assess the tolerance and efficacy of CPT-11 in combination with leucovorin-modulated bolus plus infusional 5-FU given according to the de Gramont regimen in chemonaive patients with ACC."	( Irinotecan (CPT-11) in combination with infusional 5-fluorouracil and leucovorin (de Gramont regimen) as first-line treatment in patients with advanced colorectal cancer: a multicenter phase II study. Androulakis, N; Georgoulias, V; Kakolyris, S; Kalbakis, K; Kandilis, K; Kouroussis, C; Mavroudis, D; Sarra, E; Souglakos, J; Vamvakas, L; Ziras, N, 2002)	0.31
" In this report, we have studied the in vivo activity of IMC-C225 combined with the topoisomerase I inhibitor irinotecan (CPT-11) using two models of human colorectal carcinoma in nude mice."	( Enhanced antitumor activity of anti-epidermal growth factor receptor monoclonal antibody IMC-C225 in combination with irinotecan (CPT-11) against human colorectal tumor xenografts. Bassi, R; Ellis, LM; Hicklin, DJ; Hooper, AT; Prewett, MC; Waksal, HW, 2002)	0.31
"To evaluate the efficacy and tolerance of irinotecan (CPT-11) in combination with oxaliplatin (L-OHP) plus fluorouracil (5-FU)/leucovorin (LV) (de Gramont regimen) as first-line treatment of metastatic colorectal cancer (MCC)."	( Triplet combination with irinotecan plus oxaliplatin plus continuous-infusion fluorouracil and leucovorin as first-line treatment in metastatic colorectal cancer: a multicenter phase II trial. Agelaki, S; Androulakis, N; Athanasiadis, N; Georgoulias, V; Kakolyris, S; Kalbakis, K; Kourousis, Ch; Mavroudis, D; Samonis, G; Souglakos, J; Tsetis, D; Vardakis, N, 2002)	0.31
" Thus, clinical and economic data demonstrate that irinotecan, either in combination with irinotecan plus 5-fluorouracil and folinic acid in the first line setting or as monotherapy in the second line setting, has a major role in the management of metastatic colorectal cancer."	( Clinical and economic benefits of irinotecan in combination with 5-fluorouracil and folinic acid as first line treatment of metastatic colorectal cancer. Cunningham, D; Falk, S; Jackson, D, 2002)	0.31
" Therefore, we evaluated the anti-proliferative potential of MTA combined with drugs known to exert therapeutic activity against colon cancer, including 5-fluorouracil, oxaliplatin, and SN38, the active metabolite of irinotecan."	( Pemetrexed disodium combined with oxaliplatin, SN38, or 5-fluorouracil, based on the quantitation of drug interactions in human HT29 colon cancer cells. Coudray, AM; De Gramont, A; Faivre, S; Gespach, C; Louvet, C; Raymond, E; Tournigand, C, 2002)	0.31
" The purpose of this report was to examine whether oral alkalization (OA) combined with control of defecation (CD) might prevent irinotecan-induced side effects."	( [A case-control study of prevention of irinotecan-induced diarrhea: the reducing side effects of irinotecan by oral alkalization combined with control of defecation]. Akiyama, Y; Handa, S; Kobayashi, K; Kudo, K; Kudoh, S; Soma, T; Takeda, Y, 2002)	0.31
" We have conducted a phase I trial combining these agents to find the optimal dose of irinotecan in combination with a fixed dose of cisplatin."	( Phase I study of weekly irinotecan combined with weekly cisplatin in patients with advanced solid tumors. Hara, N; Harada, T; Inoue, K; Izumi, M; Kimotsuki, K; Minami, T; Nakanishi, Y; Osaki, S; Takano, K; Takayama, K; Wataya, H, 2002)	0.31
"To determine the maximum tolerated dose (MTD) of raltitrexed when given with irinotecan and to evaluate the pharmacokinetics of these two agents when given in combination."	( Phase I and pharmacokinetic study of irinotecan in combination with raltitrexed. Adams, AL; Brady, D; Engstrom, PF; Gallo, JM; Kilpatrick, D; Lewis, NL; Litwin, S; Meropol, NJ; Scher, R; Szarka, CE; Weiner, LM, 2002)	0.31
" There have been many phase I and II clinical trials demonstrating promising results of single-agent irinotecan and combination with concurrent therapy."	( Irinotecan in combination with radiation therapy for small-cell and non-small-cell lung cancer. Choy, H; Wu, HG, 2002)	0.31
" We examined the response of three human colon tumors to TRAIL alone and in combination with chemotherapy, using SCID mice engrafted with intact patient surgical specimens."	( Effects of tumor necrosis factor-related apoptosis-inducing ligand alone and in combination with chemotherapeutic agents on patients' colon tumors grown in SCID mice. Hylander, BL; Naka, T; Repasky, EA; Rustum, YM; Sugamura, K; Widmer, MB, 2002)	0.31
"The anti-metastatic efficacy of MMI-166, which is a selective matrix metalloproteinase (MMP) inhibitor, in combination with CPT-11 was examined using two metastasis models of human gastrointestinal cancer cells."	( Augmented anti-metastatic efficacy of a selective matrix metalloproteinase inhibitor, MMI-166, in combination with CPT-11. Hojo, K; Maekawa, R; Maki, H; Sawada, TY; Tanaka, H; Yoshioka, T, 2002)	0.31
"This multicentre phase II study evaluated the efficacy and safety of irinotecan combined with the Nordic schedule of 5-fluorouracil (5-FU) and folinic acid (FA) as first-line therapy in patients with advanced colorectal cancer."	( Irinotecan combined with bolus 5-fluorouracil and folinic acid Nordic schedule as first-line therapy in advanced colorectal cancer. Boussard, B; Frödin, JE; Glimelius, B; Kjaer, M; Linné, T; Oulid-Aïssa, D; Pfeiffer, P; Pyrhönen, S; Ristamäki, R; Skovsgaard, T; Tveit, KM, 2002)	0.31
"Irinotecan combined with the bolus Nordic schedule of 5-FU/FA is active in advanced colorectal cancer with an easily managed safety profile which ensures good schedule compliance."	( Irinotecan combined with bolus 5-fluorouracil and folinic acid Nordic schedule as first-line therapy in advanced colorectal cancer. Boussard, B; Frödin, JE; Glimelius, B; Kjaer, M; Linné, T; Oulid-Aïssa, D; Pfeiffer, P; Pyrhönen, S; Ristamäki, R; Skovsgaard, T; Tveit, KM, 2002)	0.31
"Irinotecan (CPT-11) in combination with cisplatin (CDDP) has shown promising antitumor activity for advanced gastric cancer, but the optimal administration schedule of CPT-11 is still controversial."	( Pharmacokinetic study of two infusion schedules of irinotecan combined with cisplatin in patients with advanced gastric cancer. Fujitani, K; Hirao, M; Tsujinaka, T, 2003)	0.32
"Protracted infusional CPT-11 combined with CDDP is a practical regimen, and may be appropriate for a future phase II trial."	( Pharmacokinetic study of two infusion schedules of irinotecan combined with cisplatin in patients with advanced gastric cancer. Fujitani, K; Hirao, M; Tsujinaka, T, 2003)	0.32
" The MTD for irinotecan administered in combination with cisplatin (30 mg/m(2)) was 50 mg/m(2)."	( Phase I clinical and pharmacologic study of weekly cisplatin and irinotecan combined with amifostine for refractory solid tumors. Bernstein, ML; Blaney, SM; Dubowy, RL; Hershon, L; McLeod, WD; Souid, AK; Sullivan, J, 2003)	0.32
"Irinotecan hydrochloride (CPT-11) in combination with cisplatin has emerged as a new therapeutic option for the treatment of advanced gastric cancer."	( Activity and safety of a low dose, fractional administration of irinotecan hydrochloride (CPT-11) in combination with cisplatin for relapsed gastric cancer patients: a preliminary report. Aoki, F; Kaminishi, M; Mafune, K; Shimizu, N; Shimoyama, S; Tatsutomi, Y, 2003)	0.32
" The metronomic CPT-11 was combined with long-duration, low-temperature, fever-range whole body hyperthermia (FR-WBH)."	( The effect of whole-body hyperthermia combined with 'metronomic' chemotherapy on rat mammary adenocarcinoma metastases. Bull, JM; Rowe, RW; Strebel, FR; Sumiyoshi, K, )	0.13
" One cohort of five patients received ONYX-015 once a week for 6 weeks at a dose of 2 x 10(12) particles per infusion in combination with weekly infusions of irinotecan (CPT11, 125 mg per week) and 5-fluorouracil (5FU, 500 mg per week)."	( Pilot trial of intravenous infusion of a replication-selective adenovirus (ONYX-015) in combination with chemotherapy or IL-2 treatment in refractory cancer patients. Blackburn, A; Cunningham, C; Freeman, S; Gibson, B; Nemunaitis, J; Netto, G; Paulson, AS; Post, L; Randlev, B; Rich, D; Sands, B; Tong, A, 2003)	0.32
" The use of irinotecan together with raltitrexed is also being investigated, as is its combination with oxaliplatin."	( Irinotecan in metastatic colorectal cancer: dose intensification and combination with new agents, including biological response modifiers. Ducreux, M; Köhne, CH; Schwartz, GK; Vanhoefer, U, 2003)	0.32
"Three different therapeutic regimens of irinotecan (CPT-11) in combination with 5-fluorouracil (5-FU) and folinic acid (FA) were evaluated for efficacy and safety in the first-line therapy of advanced colorectal cancer."	( A randomized phase II trial of irinotecan in combination with infusional or two different bolus 5-fluorouracil and folinic acid regimens as first-line therapy for advanced colorectal cancer. Boussard, B; Bouzid, K; Khalfallah, S; Padrik, P; Piko, B; Plate, S; Pshevloutsky, EM; Purkalne, G; Serafy, M; Tujakowski, J, 2003)	0.32
" Future karenitecin clinical trials should include studies to monitor or evaluate the effects of these potential drug interactions on the overall toxicity of karenitecin when used in combination with other drugs."	( Evaluation of in vitro drug interactions with karenitecin, a novel, highly lipophilic camptothecin derivative in phase II clinical development. Hausheer, FH; Madden, T; Newman, RA; Smith, JA, 2003)	0.54
" irinotecan/5-FU/LV administered every 2 weeks, combined with HAI pirarubicin 60 mg/m(2) on day 1 every 4 weeks."	( Multimodal therapy with intravenous biweekly leucovorin, 5-fluorouracil and irinotecan combined with hepatic arterial infusion pirarubicin in non-resectable hepatic metastases from colorectal cancer (a European Association for Research in Oncology trial). Auroux, J; Aziza, T; Braud, AC; Bugat, R; Buyse, M; Cherqui, D; Dupuis, O; Fagniez, PL; Ganem, G; Guimbaud, R; Haddad, E; Kobeiter, H; Piedbois, P; Piolot, A; Tayar, C; Valleur, P; Zelek, L, 2003)	0.32
" We designed a biweekly administration regimen of TXT combined with CPT-11 for 4 weeks as one cycle in patients with inoperable or recurrent gastric cancer, and conducted a dose-escalation study."	( Biweekly administration regimen of docetaxel combined with CPT-11 in patients with inoperable or recurrent gastric cancer. Gamoh, M; Kanamaru, R; Mitachi, Y; Saitoh, S; Sakata, Y; Sekikawa, K; Terashima, M; Yoshioka, T, 2003)	0.32
" The pharmacologic features of this drug enable its combination with other antiblastic agents, such as vinorelbine, gemcitabine, paclitaxel and docetaxel."	( Antiblastic drug combinations with ifosfamide: an update. Badalamenti, G; Fulfaro, F; Gebbia, N; Russo, A; Valerio, MR, 2003)	0.32
"Although the precise molecular mechanism of interaction between brostallicin and the other tested cytotoxics has not yet been identified, a clear therapeutic gain is observed in preclinical models when brostallicin is combined with anticancer agents such as cDDP, DX, CPT-11, and Taxotere."	( Enhancement of in vivo antitumor activity of classical anticancer agents by combination with the new, glutathione-interacting DNA minor groove-binder, brostallicin. Broggini, M; Colombo, T; Geroni, C; Marchini, S; Sabatino, MA, 2003)	0.32
"The aim of the current randomized Phase II study was to investigate the efficacy and safety of capecitabine combined with irinotecan as first-line treatment in metastatic colorectal carcinoma (CRC)."	( Randomized multicenter Phase II trial of two different schedules of irinotecan combined with capecitabine as first-line treatment in metastatic colorectal carcinoma. Artale, S; Bajetta, E; Beretta, E; Biasco, G; Bonaglia, L; Bonetti, A; Buzzoni, R; Carreca, I; Cassata, A; Cortinovis, D; Di Bartolomeo, M; Ferrario, E; Frustaci, S; Iannelli, A; Lambiase, A; Mariani, L; Marini, G; Pinotti, G, 2004)	0.32
" The anti-tumor effects of the rAAV-endostatin vector combined with a topoisomerase inhibitor, etoposide, were evaluated in a mouse liver tumor model."	( Adeno-associated virus mediated endostatin gene therapy in combination with topoisomerase inhibitor effectively controls liver tumor in mouse model. Choi, SH; Hong, SY; Hyung, WJ; Jung, HC; Kim, KS; Lee, MH; Noh, SH; Roh, JK, 2004)	0.32
" Finally, the mice treated with rAAV-endostatin in combination with etoposide showed the longest survival among the experimental models."	( Adeno-associated virus mediated endostatin gene therapy in combination with topoisomerase inhibitor effectively controls liver tumor in mouse model. Choi, SH; Hong, SY; Hyung, WJ; Jung, HC; Kim, KS; Lee, MH; Noh, SH; Roh, JK, 2004)	0.32
"rAAV delivered endostatin gene therapy in combination with a topoisomerase inhibitor pretreatment is an effective modality for anticancer gene therapy."	( Adeno-associated virus mediated endostatin gene therapy in combination with topoisomerase inhibitor effectively controls liver tumor in mouse model. Choi, SH; Hong, SY; Hyung, WJ; Jung, HC; Kim, KS; Lee, MH; Noh, SH; Roh, JK, 2004)	0.32
"The aims of this study were to determine the maximum-tolerated dose (MTD), toxicity profile, and pharmacokinetics of irinotecan given with oral R115777 (tipifarnib), a farnesyl protein transferase inhibitor."	( Phase I and pharmacokinetic study of irinotecan in combination with R115777, a farnesyl protein transferase inhibitor. de Bruijn, P; de Heus, G; de Jonge, MJ; Eskens, FA; Kehrer, DF; Klaren, A; Mathijssen, RH; Palmer, PA; Planting, AS; Sparreboom, A; Verhaeghe, T; Verheij, C; Verweij, J; Xie, R; Zhang, S, 2004)	0.32
" The different drug combination schedules were tested in various concentrations by using equiactive concentrations of the two drugs."	( The schedule-dependent enhanced cytotoxic activity of 7-ethyl-10-hydroxy-camptothecin (SN-38) in combination with Gefitinib (Iressa, ZD1839). Azzariti, A; Paradiso, A; Porcelli, L; Xu, JM, 2004)	0.56
" We have examined the effect of this CDO alone and in combination with a range of common chemotherapeutic agents in colorectal cancer cell lines."	( The in vitro effects of CRE-decoy oligonucleotides in combination with conventional chemotherapy in colorectal cancer cell lines. Liu, WM; Propper, DJ; Scott, KA; Shahin, S, 2004)	0.32
"A 46-year-old Japanese female with advanced gastric cancer with positive peritoneal cytology and who was refractory to methotrexate plus 5-FU sequential chemotherapy received low-dose, fractional irinotecan hydrochloride (CPT-11) in combination with cisplatin."	( [Successful downstaging by a low-dose, fractional administration of irinotecan hydrochloride (CPT-11) in combination with cisplatin in peritoneal lavage cytology positive, 5-fluorouracil refractory advanced gastric cancer patients]. Hiki, N; Imamura, K; Kaminishi, M; Katayama, A; Mafune, K; Motoi, T; Oohashi, K; Shimizu, N; Shimoyama, S; Yamaguchi, H, 2004)	0.32
"This multicentre phase I/II study was designed to determine the maximum tolerated dose of irinotecan when combined with 5-fluorouracil and folinic acid according to the Mayo Clinic schedule and to evaluate the activity of this combination as first-line therapy in patients with advanced colorectal cancer."	( Phase I/II study of first-line irinotecan combined with 5-fluorouracil and folinic acid Mayo Clinic schedule in patients with advanced colorectal cancer. Boussard, B; Carmichael, J; Daniel, F; Davidson, N; Falk, S; Jacobs, C; Kuehr, T; Rapoport, BL; Ruff, P; Thaler, J, 2004)	0.32
"Diarrhoea was dose limiting at 300 mg/m2 irinotecan in combination with 5-fluorouracil and folinic acid, and this was determined to be the maximum tolerated dose."	( Phase I/II study of first-line irinotecan combined with 5-fluorouracil and folinic acid Mayo Clinic schedule in patients with advanced colorectal cancer. Boussard, B; Carmichael, J; Daniel, F; Davidson, N; Falk, S; Jacobs, C; Kuehr, T; Rapoport, BL; Ruff, P; Thaler, J, 2004)	0.32
"This regimen of irinotecan in combination with the Mayo Clinic schedule of bolus 5-fluorouracil/folinic acid every four weeks showed activity as first-line therapy in patients with advanced colorectal cancer."	( Phase I/II study of first-line irinotecan combined with 5-fluorouracil and folinic acid Mayo Clinic schedule in patients with advanced colorectal cancer. Boussard, B; Carmichael, J; Daniel, F; Davidson, N; Falk, S; Jacobs, C; Kuehr, T; Rapoport, BL; Ruff, P; Thaler, J, 2004)	0.32
"We evaluated the cytotoxic effect of ZD0473 administered alone or in combination with 5-Fluorouracil (5FU) or SN38 in a panel of sensitive and 5FU-resistant colorectal cell lines (HT29/HT29-5FUR and LoVo/LoVo-5FUR)."	( Antiproliferative effects of ZD0473 (AMD473) in combination with 5-fluorouracil or SN38 in human colorectal cancer cell lines. Abad, A; Martinez-Balibrea, E; Plasencia, C; Taron, M, 2004)	0.32
"CPT-11 combined with MMC can be effective against advanced or recurrent SCC of the uterine cervix."	( Phase II study of irinotecan combined with mitomycin-C for advanced or recurrent squamous cell carcinoma of the uterine cervix: the JGOG study. Fujii, T; Fushiki, H; Hasegawa, K; Izumi, R; Nishida, M; Nishimura, R; Takizawa, K; Tanaka, T; Umesaki, N; Yamamoto, K, 2004)	0.32
" The cytotoxic activity of irofulven is augmented when combined with agents that interact with DNA topoisomerase I; however, none of the reported studies have used the protracted dosing schedule found to be active clinically in treatment of childhood cancers."	( Enhanced antitumor activity of irofulven in combination with irinotecan in pediatric solid tumor xenograft models. Billups, C; Bjornsti, MA; Houghton, PJ; Liang, H; Peterson, JK; Woo, MH, 2005)	0.33
" At the same doses, irofulven in combination with irinotecan demonstrated superior antitumor activity, inducing complete responses in seven of the eight xenograft lines."	( Enhanced antitumor activity of irofulven in combination with irinotecan in pediatric solid tumor xenograft models. Billups, C; Bjornsti, MA; Houghton, PJ; Liang, H; Peterson, JK; Woo, MH, 2005)	0.33
"These studies show that the cytotoxic activity of irofulven is greater when combined with protracted administration of irinotecan."	( Enhanced antitumor activity of irofulven in combination with irinotecan in pediatric solid tumor xenograft models. Billups, C; Bjornsti, MA; Houghton, PJ; Liang, H; Peterson, JK; Woo, MH, 2005)	0.33
" Subsequently, vascular-targeted gene therapy was combined with chemotherapeutic agents."	( In vivo efficacy of HSV-TK transcriptionally targeted to the tumour vasculature is augmented by combination with cytotoxic chemotherapy. Harrington, KJ; Marshall, CJ; Mavria, G; Porter, CD, 2005)	0.33
" In colorectal tumours, combination with irinotecan, a cytotoxic drug used to treat colorectal cancer, significantly increased survival compared to drug alone."	( In vivo efficacy of HSV-TK transcriptionally targeted to the tumour vasculature is augmented by combination with cytotoxic chemotherapy. Harrington, KJ; Marshall, CJ; Mavria, G; Porter, CD, 2005)	0.33
"We show that the ppET1-targeted vector is efficacious for therapeutic gene expression in vivo, validating a strategy targeted to tumour vasculature, and demonstrate that vascular targeting combined with appropriate chemotherapy is more effective than either therapy alone."	( In vivo efficacy of HSV-TK transcriptionally targeted to the tumour vasculature is augmented by combination with cytotoxic chemotherapy. Harrington, KJ; Marshall, CJ; Mavria, G; Porter, CD, 2005)	0.33
"To establish the recommended dose (RD) of the thymidylate-synthase inhibitor ZD9331 administered with irinotecan (CPT-11) in patients with pretreated metastatic colorectal cancer, and to assess toxicity profile, pharmacokinetics (PK), and anti-tumor activity in a phase I/II open, multicenter, intrapatient chemotherapy dose escalating trial."	( A phase I-II, dose-escalating trial of ZD9331 in combination with irinotecan (CPT11) in previously pretreated metastatic colorectal cancer patients. André, T; de Gramont, A; Gamelin, E; Garcia, ML; Kalla, S; Lenaers, G; Louvet, C; Méry-Mignard, D; Saavedra, A, 2004)	0.32
"ZD9331 90 mg/m2 combined with CPT-11 180 mg/m2 may be a viable option for treatment of metastatic colorectal cancer, with possible escalation to 120 mg/m2 of ZD9331 according to safety evaluation."	( A phase I-II, dose-escalating trial of ZD9331 in combination with irinotecan (CPT11) in previously pretreated metastatic colorectal cancer patients. André, T; de Gramont, A; Gamelin, E; Garcia, ML; Kalla, S; Lenaers, G; Louvet, C; Méry-Mignard, D; Saavedra, A, 2004)	0.32
"5-Fluorouracil (5-FU) and capecitabine alone and in combination with irinotecan/oxaliplatin are clinically active in the treatment of colorectal and other solid tumors."	( Synergistic antitumor activity of capecitabine in combination with irinotecan. Cao, S; Durrani, FA; Rustum, YM, 2005)	0.33
"To assess the maximum tolerated dose, dose-limiting toxicity, pharmacokinetics, and preliminary antitumor activity of oral irinotecan given in combination with capecitabine to patients with advanced, refractory solid tumors."	( Phase I and pharmacokinetic study of oral irinotecan given once daily for 5 days every 3 weeks in combination with capecitabine in patients with solid tumors. Assadourian, S; deJonge, MJ; Dumez, H; Eskens, FA; Sanderink, GJ; Selleslach, J; Semiond, D; Soepenberg, O; Sparreboom, A; ter Steeg, J; van Oosterom, AT; Verweij, J, 2005)	0.33
" With irinotecan 60 mg/m2/d and capecitabine 2 x 800 mg/m2/d, grade 3 delayed diarrhea in combination with grade 2 nausea (despite maximal antiemetic support) and grade 3 anorexia and colitis, were the first-cycle dose-limiting toxicities in two of six patients, respectively."	( Phase I and pharmacokinetic study of oral irinotecan given once daily for 5 days every 3 weeks in combination with capecitabine in patients with solid tumors. Assadourian, S; deJonge, MJ; Dumez, H; Eskens, FA; Sanderink, GJ; Selleslach, J; Semiond, D; Soepenberg, O; Sparreboom, A; ter Steeg, J; van Oosterom, AT; Verweij, J, 2005)	0.33
"To establish the feasibility and efficacy of capecitabine in combination with weekly irinotecan (CAPIRI) with concurrent pelvic radiotherapy (RT) in patients with locally advanced rectal cancer."	( Phase I trial of capecitabine and weekly irinotecan in combination with radiotherapy for neoadjuvant therapy of rectal cancer. Gnad, U; Hehlmann, R; Hochhaus, A; Hofheinz, RD; Kraus-Tiefenbacher, U; Müldner, A; Post, S; von Gerstenberg-Helldorf, B; Wenz, F; Willeke, F, 2005)	0.33
" In the present study, the antitumour activity of XR5944 was investigated in combination with 5-fluorouracil (5-FU) or irinotecan in human colon carcinoma cell lines and xenografts."	( Antitumour activity of XR5944 in vitro and in vivo in combination with 5-fluorouracil and irinotecan in colon cancer cell lines. Brown, JL; Charlton, PA; Freathy, C; Harris, SM; Mistry, P, 2005)	0.33
"Dex combined with GS markedly decreased the occurrence ratio and lasting time of the symptoms such as nausea, vomiting, fever and pain, and protected the function of liver as compared with the placebo (P<0."	( [Ginsenosides combined with dexamethasone in preventing and treating postembolization syndrome following transcatheter arterial chemoembolization: a randomized, controlled and double-blinded prospective trial]. Chen, Z; Feng, YL; Li, B; Ling, CQ; Yu, CQ; Zhu, DZ, 2005)	0.33
"Dex combined with GS can effectively prevent and treat the postembolization syndrome following TACE."	( [Ginsenosides combined with dexamethasone in preventing and treating postembolization syndrome following transcatheter arterial chemoembolization: a randomized, controlled and double-blinded prospective trial]. Chen, Z; Feng, YL; Li, B; Ling, CQ; Yu, CQ; Zhu, DZ, 2005)	0.33
" This phase I pharmacokinetic and clinical study evaluated escalating CPT-11 doses administered every 3 weeks combined with a fixed dose of 5-FU CI over 14 days to find the maximum tolerated dose (MTD) of this combined chemotherapy."	( A phase I, dose-finding study of irinotecan (CPT-11) short i.v. infusion combined with fixed dose of 5-fluorouracil (5-FU) protracted i.v. infusion in adult patients with advanced solid tumours. Alfonso, R; Carcas, A; Cortés-Funes, H; Díaz-Rubio, E; Frías, J; Grávalos, C; Guerra, P; Paz-Ares, L; Pronk, L; Sastre, J, 2005)	0.33
" In step 3, the recommended dose of CPT-11 was divided and administered in a weekly schedule for 4 weeks combined with a fixed dose of 5-FU CI 250 mg/m(2), and then followed by 2-5 weeks rest."	( A phase I, dose-finding study of irinotecan (CPT-11) short i.v. infusion combined with fixed dose of 5-fluorouracil (5-FU) protracted i.v. infusion in adult patients with advanced solid tumours. Alfonso, R; Carcas, A; Cortés-Funes, H; Díaz-Rubio, E; Frías, J; Grávalos, C; Guerra, P; Paz-Ares, L; Pronk, L; Sastre, J, 2005)	0.33
"To obtain data on drug-drug interactions with irinotecan and oxaliplatin, a literature search of PubMed and EMBASE was conducted using the search terms irinotecan, oxaliplatin, and interactions (English-language studies only published between 1980 and August 2004)."	( Classification and occurrence of clinically significant drug interactions with irinotecan and oxaliplatin in patients with metastatic colorectal cancer. Brouwers, JR; Coenen, JL; de Graaf, JC; Idzinga, FS; Jansman, FG; Sleijfer, DT; Smit, WM, 2005)	0.33
" This study was performed to determine the efficacy and safety of irinotecan (CPT-11) in combination with fluorouracil (FU) administered as a 48-hour continuous infusion twice a month in elderly patients."	( Irinotecan in combination with fluorouracil in a 48-hour continuous infusion as first-line chemotherapy for elderly patients with metastatic colorectal cancer: a Spanish Cooperative Group for the Treatment of Digestive Tumors study. Abad, A; Antón, A; Aranda, E; Carrato, A; Díaz-Rubio, E; Gil, S; Maestu, I; Marcuello, E; Masutti, B; Maurel, J; Navarro, M; Sastre, J; Valladares, M; Vicent, JM, 2005)	0.33
"Twice a month continuous-infusion CPT-11 combined with FU is a valid therapeutic alternative for elderly patients in good general condition."	( Irinotecan in combination with fluorouracil in a 48-hour continuous infusion as first-line chemotherapy for elderly patients with metastatic colorectal cancer: a Spanish Cooperative Group for the Treatment of Digestive Tumors study. Abad, A; Antón, A; Aranda, E; Carrato, A; Díaz-Rubio, E; Gil, S; Maestu, I; Marcuello, E; Masutti, B; Maurel, J; Navarro, M; Sastre, J; Valladares, M; Vicent, JM, 2005)	0.33
" Results showed a reduced sensitivity of melanoma cells to gimatecan following Bcl-2 transfection and inversely, increased cell sensitivity to gimatecan in combination with oblimersen."	( Enhanced antitumour efficacy of gimatecan in combination with Bcl-2 antisense oligonucleotide in human melanoma xenografts. Balsari, A; Carenini, N; De Cesare, M; Del Bufalo, D; Perego, P; Pratesi, G; Righetti, SC; Rivoltini, L; Zunino, F; Zupi, G, 2005)	0.33
"To explore the efficacy and safety of CPT-11 combined with fluoropyrimidine in treatment for advanced or metastatic colorectal carcinoma."	( [Irinotecan combined with fluoropyrimidine in treatment for advanced/metastatic colorectal carcinoma]. Wu, WQ; Yu, BM, 2005)	0.33
" CPT-11 combined with capecitabine are not only more effective, but also its occurrence of side effect is lowered, and are especially high effective for lung metastasis."	( [Irinotecan combined with fluoropyrimidine in treatment for advanced/metastatic colorectal carcinoma]. Wu, WQ; Yu, BM, 2005)	0.33
"The aim of this study was to determine in patients with previously untreated advanced colorectal cancer the maximum tolerated dose (MTD) and safety profile of irinotecan in combination with capecitabine, to identify a recommended dose and to determine the response rate and time to disease progression."	( A phase I/II and pharmacokinetic study of irinotecan in combination with capecitabine as first-line therapy for advanced colorectal cancer. Bakker, JM; Falk, S; Groenewegen, G; Kerr, DJ; Maughan, T; Nortier, JW; Punt, CJ; Rea, DW; Richel, DJ; Semiond, D; Smit, JM; Steven, N; Ten Bokkel Huinink, WW, 2005)	0.33
"Patients with solid tumors received one of three escalating dose levels of daily celecoxib in combination with docetaxel and irinotecan administered on days 1 and 8 of an every 21-day cycle."	( A phase I trial of celecoxib in combination with docetaxel and irinotecan in patients with advanced cancer. Adjei, AA; Croghan, GC; Dy, GK; Furth, A; Hanson, LJ; Mandrekar, S; Okuno, SH; Peethambaram, PP, 2005)	0.33
" In this study, we investigated the anticancer activity of BGC9331 either alone or combined with 5-fluorouracil (5-FU), MTA (multi-target antifolate), oxali-platin and SN-38, the active metabolite of the topoisomerase I inhibitor CPT-11."	( Increased anticancer activity of the thymidylate synthase inhibitor BGC9331 combined with the topoisomerase I inhibitor SN-38 in human colorectal and breast cancer cells: induction of apoptosis and ROCK cleavage through caspase-3-dependent and -independen André, T; Coudray, AM; De Gramont, A; Faivre, S; Gespach, C; Kornprobst, M; Larsen, AK; Louvet, C; Raymond, E; Tournigand, C, 2005)	0.33
" Due to the difference of concentration between batches containing irinotecan or topotecan, HPLC and HPTLC both combined with fluorescence detection were investigated."	( Fluorescence detection combined with either HPLC or HPTLC for pharmaceutical quality control in a hospital chemotherapy production unit: application to camptothecin derivatives. Bourget, P; Gravel, E; Mercier, L; Paci, A, 2005)	0.53
" This new oncolytic virus (MGH2) displays increased antitumor efficacy against human glioma cells both in vitro and in vivo when combined with cyclophosphamide and CPT-11."	( Brain tumor oncolysis with replication-conditional herpes simplex virus type 1 expressing the prodrug-activating genes, CYP2B1 and secreted human intestinal carboxylesterase, in combination with cyclophosphamide and irinotecan. Chiocca, EA; Danks, MK; Finkelstein, DM; Hyatt, JL; Leroy, S; Potter, PM; Saeki, Y; Terada, K; Tyminski, E, 2005)	0.33
" Treatment with triple therapy using octreotide, galanin and serotonin appear to be comparable to 5-FU/LV in combination with irinotecan and oxaliplatin."	( Comparison between triple therapy with octreotide, galanin and serotonin vs. irinotecan or oxaliplatin in combination with 5-fluorouracil/leukovorin in human colon cancer. El-Salhy, M; Hilding, L; Royson, H; Tjomsland, V, 2005)	0.33
"Irinotecan (CPT-11) in combination with 5-fluorouracil/folinic acid is used successfully for first-line treatment of metastatic colorectal cancer."	( Pharmacokinetics and metabolism of irinotecan combined with capecitabine in patients with advanced colorectal cancer. Czejka, M; Hauer, K; Ostermann, E; Schueller, J, )	0.13
"A dose-escalation study of irinotecan (CPT-11) combined with S-1, a novel oral fluoropyrimidine, was performed to determine the maximum-tolerated dose (MTD), recommended dose (RD) and dose-limiting toxicities (DLTs) in advanced gastric cancer."	( Phase I study of S-1 combined with irinotecan (CPT-11) in patients with advanced gastric cancer (OGSG 0002). Fujitani, K; Furukawa, H; Gotoh, M; Iishi, H; Katsu, K; Kawabe, S; Narahara, H; Taguchi, T; Takiuchi, H; Tatsuta, M; Tsujinaka, T, 2005)	0.33
"The efficacy of oxaliplatin combined with capecitabine (XELOX) as second-line therapy in patients with advanced colorectal cancer (ACRC) resistant to irinotecan is not well established."	( Short-time infusion of oxaliplatin in combination with capecitabine (XELOX30) as second-line therapy in patients with advanced colorectal cancer after failure to irinotecan and 5-fluorouracil. Baltesgard, L; Ehrsson, H; Fokstuen, T; Glimelius, B; Mortensen, JP; Pfeiffer, P; Qvortrup, C; Starkhammar, H; Sørbye, H; Tveit, KM; Wallin, I; Øgreid, D, 2006)	0.33
" Bevacizumab is currently approved for the first-line treatment of metastatic CRC and is currently being tested in combination with standard therapies for a range of indications."	( Bevacizumab combined with standard fluoropyrimidine-based chemotherapy regimens to treat colorectal cancer. Hurwitz, H; Kabbinavar, F, 2005)	0.33
" The patient was treated with TS-1 combined with CPT-11."	( [A case of an increase in resectability with preoperative chemotherapy TS-1 combined with CPT-11 for unresectable rectal cancer in downstaging]. Doi, M; Egawa, T; Hayashi, S; Kitano, M; Nagashima, A; Yoshii, H, 2005)	0.33
"The maximum tolerated dose for this combination with granulocyte-colony-stimulating factor support was identified as imatinib at a dose of 300 mg/day with irinotecan (at a dose of 65 mg/m(2)) and cisplatin (at a dose of 30 mg/m(2)) given on Days 1 and 8, every 21 days."	( Phase I studies of imatinib mesylate combined with cisplatin and irinotecan in patients with small cell lung carcinoma. Glisson, BS; Johnson, FM; Krug, LM; Patel, J; Peeples, B; Prieto, VG; Shoaf, S; Tamboli, P; Tran, HT, 2006)	0.33
"Irinotecan, when combined with cisplatin, is an effective treatment for advanced non-small cell lung cancer (NSCLC)."	( Phase I study of cisplatin and irinotecan combined with concurrent hyperfractionated accelerated thoracic radiotherapy for locally advanced non-small cell lung carcinoma. Asaka-Amano, Y; Itoh, H; Kasahara, Y; Kuriyama, T; Kurosu, K; Takiguchi, Y; Tanabe, N; Tatsumi, K; Uno, T; Uruma, R, 2005)	0.33
" The protocol consisted of escalating doses of irinotecan on days 1 and 15, and daily low-dose cisplatin (6 mg/m(2) daily for a total dose of 120 mg/m(2)) combined with concurrent hyperfractionated accelerated thoracic irradiation (1."	( Phase I study of cisplatin and irinotecan combined with concurrent hyperfractionated accelerated thoracic radiotherapy for locally advanced non-small cell lung carcinoma. Asaka-Amano, Y; Itoh, H; Kasahara, Y; Kuriyama, T; Kurosu, K; Takiguchi, Y; Tanabe, N; Tatsumi, K; Uno, T; Uruma, R, 2005)	0.33
" Furthermore, the efficacy of immunotherapy combined with either 5-fluorouracil or irinotecan was similar to that of immunotherapy alone."	( Immunotherapy with dendritic cells and CpG oligonucleotides can be combined with chemotherapy without loss of efficacy in a mouse model of colon cancer. Beck, S; Bourquin, C; Endres, S; Hartmann, G; Schreiber, S, 2006)	0.33
" This study investigated activated/phosphorylated EGFR (pEGFR) in 23 patients with EGFR-positive metastatic colorectal cancer refractory to irinotecan and treated with cetuximab, alone or in combination with irinotecan."	( Correlation between the response to cetuximab alone or in combination with irinotecan and the activated/phosphorylated epidermal growth factor receptor in metastatic colorectal cancer. Barette, M; Bleiberg, H; Cardoso, F; Galdon, MG; Gallez, J; Hendlisz, A; Larsimont, D; Nagy, N; Paesmans, M; Personeni, N; Van Laethem, JL, 2005)	0.33
"We designed and conducted an NCI-sponsored trial to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of semaxanib given twice weekly in combination with weekly irinotecan in patients with advanced colorectal cancer who had failed at least one prior treatment."	( A Phase I study of escalating doses of the tyrosine kinase inhibitor semaxanib (SU5416) in combination with irinotecan in patients with advanced colorectal carcinoma. Abbruzzese, JL; Bogaard, K; Hoff, PM; Waldrum, S; Wolff, RA, 2006)	0.33
" After 33 months, a high dose of CDDP was administered twice in combination with TS-1, because elevation of serum CEA levels and paraortic lymphnode swelling were observed for the first time."	( [A case of gastric cancer with peritoneal dissemination who achieved five-year survival by successive treatments with TS-1 alone and in combination with other drugs]. Aiko, S; Ishizuka, T; Kumano, I; Maehara, T; Sakano, T; Sugiura, Y; Yoshizumi, Y, 2006)	0.33
"A dose-escalation study of irinotecan (CPT-11) combined with S-1, an oral dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine, was performed to determine the maximum-tolerated dose (MTD), recommended dose (RD), dose-limiting toxicities (DLTs), and objective response rate (RR) in advanced gastric cancer (AGC)."	( Phase I/II study of S-1 combined with irinotecan for metastatic advanced gastric cancer. Ichikawa, W; Inokuchi, M; Kawano, T; Kojima, K; Nihei, Z; Sugihara, K; Yamada, H; Yamashita, T, 2006)	0.33
"Twice weekly SU5416 can be administered with bolus IFL without unexpected toxicities or altering the pharmacokinetic behavior of the administered drugs."	( Phase I/pilot study of SU5416 (semaxinib) in combination with irinotecan/bolus 5-FU/LV (IFL) in patients with metastatic colorectal cancer. Berlin, JD; Cropp, GF; Donnelly, E; Fleischer, AC; Hande, KR; Hannah, AL; Lockhart, AC; Rothenberg, ML; Schaaf, LJ; Schumaker, RD, 2006)	0.33
"To establish a safe and practical chemotherapeutic regimen using CPT-11 in combination with 5-FU plus leucovorin (5-FU/LV) for patients with metastatic colorectal cancer in an outpatient setting, a phase I clinical trial was conducted."	( A phase I trial of CPT-11 in combination with 5-fluorouracil plus leucovorin chemotherapy for patients with metastatic colorectal cancer. Emi, M; Kawabuchi, Y; Minami, K; Yamaguchi, Y, )	0.13
"These results suggest that our treatment regimen using CPT-11 in combination with 5-FU/LV is a safe regimen in an outpatient setting and effective for patients with metastatic colorectal cancer."	( A phase I trial of CPT-11 in combination with 5-fluorouracil plus leucovorin chemotherapy for patients with metastatic colorectal cancer. Emi, M; Kawabuchi, Y; Minami, K; Yamaguchi, Y, )	0.13
"No significant alterations in the plasma concentrations and pharmacokinetics of irinotecan and its metabolites were observed after combination with cetuximab."	( In vivo disposition of irinotecan (CPT-11) and its metabolites in combination with the monoclonal antibody cetuximab. Czejka, M; Ettlinger, DE; Farkouh, A; Mitterhauser, M; Ostermann, E; Schueller, J; Wadsak, W, )	0.13
" A third pharmacokinetic study was to determine the appropriate dose of intraperitoneal oxaliplatin combined with intraperitoneal irinotecan: the recommended dosage was 360 mg/m2 for each of the chemotherapy agents."	( Heated intra-operative intraperitoneal oxaliplatin alone and in combination with intraperitoneal irinotecan: Pharmacologic studies. Bonnay, M; Elias, D; Pocard, M; Raynard, B, 2006)	0.33
"To determine the efficacy and toxicity of irinotecan combined with carboplatin, we conducted a phase II trial."	( Phase II study of irinotecan combined with carboplatin in previously untreated small-cell lung cancer. Fukuda, M; Kinoshita, A; Kohno, S; Kuba, M; Nagashima, S; Nakamura, Y; Oka, M; Soda, H; Takatani, H; Tsurutani, J, 2006)	0.33
"Recent clinical studies have demonstrated a reduction of irinotecan (CPT-11) gastrointestinal toxicities when the CPT-11 is administered in combination with thalidomide in patients with diagnosis of colorectal cancer."	( Irinotecan in combination with thalidomide in patients with advanced solid tumors: a clinical study with pharmacodynamic and pharmacokinetic evaluation. Allegrini, G; Amatori, F; Bocci, G; Cerri, E; Cupini, S; Danesi, R; Del Tacca, M; Di Paolo, A; Falcone, A; Marcucci, L; Masi, G, 2006)	0.33
" Pharmacokinetic data suggested a decreased metabolism of irinotecan into SN-38 and SN-38-glucuronide when it was administered with thalidomide."	( Irinotecan in combination with thalidomide in patients with advanced solid tumors: a clinical study with pharmacodynamic and pharmacokinetic evaluation. Allegrini, G; Amatori, F; Bocci, G; Cerri, E; Cupini, S; Danesi, R; Del Tacca, M; Di Paolo, A; Falcone, A; Marcucci, L; Masi, G, 2006)	0.33
" It is possible that lamivudine combined with chemotherapy may have had a therapeutic effect on ATL in this case."	( [Development of acute type, CD 8 positive adult T-cell leukemia in a carrier of hepatitis B virus--possible therapeutic effect of lamivudine combined with chemotherapy]. Hasegawa, H; Miyagi, T; Nagasaki, A; Nakachi, S; Shinzato, O; Taira, N; Takasu, N; Tomoyose, T, 2006)	0.33
"To evaluate the efficacy of Avastin in combination with irinotecan for metastatic colorectal cancer."	( [Efficacy of Avastin in combination with irinotecan for metastatic colorectal cancer]. Chen, JZ; Liao, WJ; Luo, RC; Zheng, H, 2006)	0.33
"A combination phase I study was conducted in a cohort of lung cancer patients to determine the maximum tolerated dose (MTD) and toxicities of irinotecan (CPT-11), a topoisomerase I inhibitor, in combination with amrubicin (AMR), a topoisomerase II inhibitor, and to observe their antitumor activities."	( A phase I study of irinotecan in combination with amrubicin for advanced lung cancer patients. Fukuoka, M; Kaneda, H; Kurata, T; Nakagawa, K; Tamura, K; Uejima, H, )	0.13
" Because of its wide spectrum of actions, it is reasonable to consider the combination with other anticancer drugs in clinical application."	( Cytotoxic effects of histone deacetylase inhibitor FK228 (depsipeptide, formally named FR901228) in combination with conventional anti-leukemia/lymphoma agents against human leukemia/lymphoma cell lines. Akutsu, M; Furukawa, Y; Izumi, T; Kano, Y; Kobayashi, H; Mano, H; Tsunoda, S, 2007)	0.34
"Patients with untreated advanced colorectal cancer were enrolled to this single arm phase II multi-center cooperative group trial of bevacizumab combined with IFL."	( A phase II study of high-dose bevacizumab in combination with irinotecan, 5-fluorouracil, leucovorin, as initial therapy for advanced colorectal cancer: results from the Eastern Cooperative Oncology Group study E2200. Benson, AB; Catalano, PJ; Giantonio, BJ; Levy, DE; Meropol, NJ; O'dwyer, PJ, 2006)	0.33
" We designed a new regimen to evaluate the efficacy and feasibility of weekly low dose CPT-11 combined with 5-FU/l-LV therapy based on an RPMI regimen against advanced and recurrent colorectal cancer."	( [Evaluation of weekly low-dose CPT-11 combined with 5-FU/l-LV therapy for advanced and recurrent colorectal cancer--preliminary study]. Deguchi, Y; Kaneko, I; Kii, E; Murata, T; Sonoda, K; Tsubono, M; Yasuda, K, 2006)	0.33
" Hyperthermia has been shown to enhance the cytotoxic effect of some anticancer drugs and has been combined with intraperitoneal chemotherapy for the treatment of colorectal peritoneal carcinomatosis."	( In vitro thermochemotherapy of colon cancer cell lines with irinotecan alone and combined with mitomycin C. Benhamed, M; Chipponi, J; Gilly, FN; Glehen, O; Kwiatkowski, F; Le Page, S; Mohamed, F; Paulin, C; Pezet, D, )	0.13
" After that his general condition recovered, and two cycles of neoadjuvant chemotherapy (NAC) by irinotecan combined with 5-fluorouracil and l-leucovorin (IFL) therapy were performed on an outpatient basis."	( [A case of advanced rectal carcinoma with multiple lung metastases responding to irinotecan combined with 5-fluorouracil and l-leucovorin (IFL) as neoadjuvant chemotherapy (NAC)]. Fukada, T; Hasegawa, A; Hashimoto, R; Hayashi, T; Kametaka, H; Kawano, H; Koyama, T; Seike, K; Tanaka, H; Yasuno, K, 2006)	0.33
"Irinotecan at 180 mg/m2 combined with an infusional 5-fluorouracil/leucovorin (5-FU/LV) regimen (FOLFIRI) is a standard first line therapy for metastatic colorectal cancer (mCRC)."	( Multicentre phase II study using increasing doses of irinotecan combined with a simplified LV5FU2 regimen in metastatic colorectal cancer. Bressole, F; Chalbos, P; Debrigode, C; Desseigne, F; Duffour, J; Gourgou, S; Mineur, L; Pinguet, F; Poujol, S; Ychou, M, 2007)	0.34
"Patients received FOLFIRI every 2 weeks for up to six cycles, comprising a 5-FU/LV regimen combined with irinotecan at 180 mg/m2 (cycle 1), increasing to 220 mg/m2 (cycle 2) and 260 mg/m2 (cycle 3 and subsequent cycles) dependent on toxicity."	( Multicentre phase II study using increasing doses of irinotecan combined with a simplified LV5FU2 regimen in metastatic colorectal cancer. Bressole, F; Chalbos, P; Debrigode, C; Desseigne, F; Duffour, J; Gourgou, S; Mineur, L; Pinguet, F; Poujol, S; Ychou, M, 2007)	0.34
" Antineoplastic activity of LY293111 has been identified in preclinical models both alone and in combination with chemotherapy agents including irinotecan."	( A phase I study of oral LY293111 given daily in combination with irinotecan in patients with solid tumours. Baetz, T; Brail, LH; de Alwis, DP; Doppler, K; Eisenhauer, E; Fisher, B; Khan, AZ; MacLean, M; Moore, M; Siu, L; Walsh, W; Weitzman, A, 2007)	0.34
"Dose limiting toxicity (DLT) of grade 3 diarrhea was seen in two patients with doses of irinotecan 300 mg/m(2) IV every 21-days in combination with LY293111 300 mg BID."	( A phase I study of oral LY293111 given daily in combination with irinotecan in patients with solid tumours. Baetz, T; Brail, LH; de Alwis, DP; Doppler, K; Eisenhauer, E; Fisher, B; Khan, AZ; MacLean, M; Moore, M; Siu, L; Walsh, W; Weitzman, A, 2007)	0.34
"The recommended phase II dose of LY293111 is 600 mg orally BID in combination with irinotecan 250 mg/m(2) IV every 21-days."	( A phase I study of oral LY293111 given daily in combination with irinotecan in patients with solid tumours. Baetz, T; Brail, LH; de Alwis, DP; Doppler, K; Eisenhauer, E; Fisher, B; Khan, AZ; MacLean, M; Moore, M; Siu, L; Walsh, W; Weitzman, A, 2007)	0.34
"The purpose of this phase II study was to evaluate the efficacy and safety of cetuximab combined with FOLFIRI as a first-line treatment of advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma."	( Phase II study of cetuximab in combination with FOLFIRI in patients with untreated advanced gastric or gastroesophageal junction adenocarcinoma (FOLCETUX study). Berardi, R; Cascinu, S; Ceccarelli, C; Di Fabio, F; Funaioli, C; Giannetta, L; Giaquinta, S; Longobardi, C; Martoni, AA; Mutri, V; Piana, E; Pinto, C; Rojas Llimpe, FL; Siena, S, 2007)	0.34
" This phase I/II dose-finding study evaluated gefitinib in combination with a 5-fluorouracil (5-FU)/folinic acid (FA)/irinotecan (FOLFIRI-AIO) regimen in patients with metastatic colorectal cancer."	( Gefitinib in combination with 5-fluorouracil (5-FU)/folinic acid and irinotecan in patients with 5-FU/oxaliplatin- refractory colorectal cancer: a phase I/II study of the Arbeitsgemeinschaft für Internistische Onkologie (AIO). Arnold, D; Hochhaus, A; Hofheinz, RD; Kubicka, S; Wollert, J, 2006)	0.33
" Only the initial 1 course was administered with 5-FU (500 mg/body) as an inpatient, and further courses were performed as an outpatient with no severe adverse events."	( A case report--The marked response to gemcitabine combined with irinotecan and low-dose cisplatin chemotherapy for advanced gastric cancer with multiple liver metastases. Fujiwara, T; Gochi, A; Kagawa, S; Tanaka, N; Teraishi, F; Uno, F, 2006)	0.33
" This was the first case of esophageal small cell carcinoma treated by EMR combined with chemoradiotherapy."	( [Superficial small cell carcinoma of esophagus treated by endoscopic mucosal resection combined with chemoradiotherapy--a case report]. Hashimoto, T; Izumi, Y; Kato, T; Kawada, K; Miura, A; Momma, K; Oota, M, 2007)	0.34
"To assess the optimal regimen and its mechanism of ZD1839 in combination with SN38, the active metabolite of irinotecan (CPT-11), in the colon cancer cell lines HT-29 and LoVo."	( [Experimental study of effect of epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 in combination with irinotecan]. Azzariti, A; Han, Y; Li, YM; Li, ZQ; Paradiso, A; Wang, Y; Xu, JM; Yang, WW; Yuan, SJ; Zhao, CH, 2006)	0.33
"This randomised phase II study evaluates the safety and efficacy profile of uracil/tegafur/leucovorin combined with irinotecan (TEGAFIRI) or with oxaliplatin (TEGAFOX)."	( Uracil/ftorafur/leucovorin combined with irinotecan (TEGAFIRI) or oxaliplatin (TEGAFOX) as first-line treatment for metastatic colorectal cancer patients: results of randomised phase II study. Aitini, E; Bajetta, E; Barone, C; Buzzoni, R; Di Bartolomeo, M; Ferrario, E; Iop, A; Isa, L; Jacobelli, S; Lo Vullo, S; Mariani, L; Pinotti, G; Recaldin, E; Zilembo, N, 2007)	0.34
"To estimate the antitumor activity and toxicity of irinotecan alone and in combination with vincristine when administered as window therapy and in combination with standard chemotherapy in pediatric patients with newly diagnosed metastatic rhabdomyosarcoma."	( Two consecutive phase II window trials of irinotecan alone or in combination with vincristine for the treatment of metastatic rhabdomyosarcoma: the Children's Oncology Group. Breitfeld, P; Crews, KR; Donaldson, SS; Houghton, P; Lyden, E; Meyer, WH; Pappo, AS; Parham, D; Wiener, E, 2007)	0.34
"We sought to evaluate the efficacy and safety data of a combination regimen using weekly irinotecan in combination with capecitabine and concurrent radiotherapy (CapIri-RT) as neoadjuvant treatment in rectal cancer in a phase-II trial."	( A phase II study of capecitabine and irinotecan in combination with concurrent pelvic radiotherapy (CapIri-RT) as neoadjuvant treatment of locally advanced rectal cancer. Grobholz, R; Hochhaus, A; Hofheinz, RD; Horisberger, K; Kähler, G; Kraus-Tiefenbacher, U; Leitner, A; Post, S; Wenz, F; Willeke, F; Willer, A, 2007)	0.34
"The objective of this study was to determine the maximum tolerated dose and dose-limiting toxicity (DLT) of carboplatin in combination with gemcitabine and irinotecan in patients with solid tumors."	( Phase I study of carboplatin in combination with gemcitabine and irinotecan in patients with solid tumors: preliminary evidence of activity in small cell and neuroendocrine carcinomas. Antonia, S; Chiappori, A; de Lima Lopes, G; Haura, E; Langevin, M; Lush, R; Rocha-Lima, CM; Simon, G; Sullivan, D, 2007)	0.34
"Carboplatin in combination with gemcitabine and irinotecan was feasible."	( Phase I study of carboplatin in combination with gemcitabine and irinotecan in patients with solid tumors: preliminary evidence of activity in small cell and neuroendocrine carcinomas. Antonia, S; Chiappori, A; de Lima Lopes, G; Haura, E; Langevin, M; Lush, R; Rocha-Lima, CM; Simon, G; Sullivan, D, 2007)	0.34
"We conducted a randomised phase II study to compare irinotecan monotherapy with irinotecan in combination with infusional 5-fluorouracil/folinic acid (5-FU/FA) regarding efficacy and safety of these regimens in second-line therapy after failed fluoropyrimidine therapy in patients with metastatic colorectal cancer (mCRC)."	( A randomised phase II study of irinotecan in combination with 5-FU/FA compared with irinotecan alone as second-line treatment of patients with metastatic colorectal carcinoma. Arnold, D; Graeven, U; Heuer, T; Nusch, A; Porschen, R; Reinacher-Schick, A; Schmiegel, W, 2007)	0.34
"Our study confirms that irinotecan alone or in combination with infusional 5-FU/FA is an effective and safe regimen for CRC patients who failed first-line therapies."	( A randomised phase II study of irinotecan in combination with 5-FU/FA compared with irinotecan alone as second-line treatment of patients with metastatic colorectal carcinoma. Arnold, D; Graeven, U; Heuer, T; Nusch, A; Porschen, R; Reinacher-Schick, A; Schmiegel, W, 2007)	0.34
"The effects of the anticancer drug irinotecan combined with ethanolic extract of propolis (EEP), a water-soluble derivate of propolis (WSDP), quercetin and naringin on the growth of Ehrlich ascites tumor (EAT) and the life span of tumor-bearing Swiss albino mice were studied."	( Enhanced antitumor activity of irinotecan combined with propolis and its polyphenolic compounds on Ehrlich ascites tumor in mice. Basic, I; Benkovic, V; Bevanda, M; Brozovic, G; Dikic, D; Horvat Knezevic, A; Knezevic, F; Orsolic, N, 2007)	0.34
"APC and SN-38 exposure decreased when administered in combination with UCN-01."	( Phase I and pharmacokinetic study of UCN-01 in combination with irinotecan in patients with solid tumors. Baker, SD; Carducci, MA; Dancey, J; Donehower, RC; Hidalgo, M; Jimeno, A; Laheru, DA; Messersmith, WA; Purcell, T; Rudek, MA, 2008)	0.35
"We evaluated whether the expression of measles virus fusogenic membrane glycoproteins H and F (MV-FMG), encoded by a herpes simplex virus type 1 (HSV-1) amplicon vector, can serve with or without viral oncolysis (G47Delta) and facultative irinotecan chemotherapy, alone or in combination with the monoclonal epidermal growth factor receptor (EGFR) inhibitory antibody cetuximab, as a platform for inducing tumor-specific immune responses against colon cancer."	( Local and distant immune-mediated control of colon cancer growth with fusogenic membrane glycoproteins in combination with viral oncolysis. Bayer, W; Hoffmann, D; Wildner, O, 2007)	0.34
"To evaluate the lethal effect of adenovirus-mediated HSV-TK-ganciclovir (GCV) gene therapy in combination with hydroxycamptothecin (HCPT) on hunman bladder carcinoma cell line T-24 cells."	( [Lethal effect of adenovirus-mediated HSV-TK gene in combination with hydroxycamptothecin on human bladder cancer in vitro]. Huang, H; Liang, ZK; Tan, WL; Zhu, WH, 2007)	0.78
" GCV alone and GCV in combination with HCPT both resulted in significantly decreased survival rate of human bladder carcinoma cells (P=0."	( [Lethal effect of adenovirus-mediated HSV-TK gene in combination with hydroxycamptothecin on human bladder cancer in vitro]. Huang, H; Liang, ZK; Tan, WL; Zhu, WH, 2007)	0.57
"HSV-TK/GCV in combination with HCPT can enhance the lethal effect of suicide gene therapy against human bladder carcinoma cells and effectively induce apoptosis of the cells."	( [Lethal effect of adenovirus-mediated HSV-TK gene in combination with hydroxycamptothecin on human bladder cancer in vitro]. Huang, H; Liang, ZK; Tan, WL; Zhu, WH, 2007)	0.57
" Resection of liver metastases from SBA combined with neoadjuvant and adjuvant chemotherapy can result in extended disease-free survival and should undergo further investigation."	( Resection of small bowel adenocarcinoma liver metastasis combined with neoadjuvant and adjuvant chemotherapy results in extended disease-free period--a case report. Eigenbrod, T; Klebl, F; Kullmann, F, 2006)	0.33
"This study determined the optimally tolerated regimen (OTR) of oral lapatinib administered in combination with infusional 5-fluorouracil (5-FU), leucovorin and irinotecan (FOLFIRI) and assessed the safety, tolerability and pharmacokinetics of the combination."	( A phase I and pharmacokinetic study of lapatinib in combination with infusional 5-fluorouracil, leucovorin and irinotecan. Flaherty, KT; Fleming, RA; Kerr, DJ; Koch, KM; Middleton, MR; Midgley, RS; O'Dwyer, PJ; Pratap, SE; Smith, DA; Stevenson, JP; Versola, M; Ward, C, 2007)	0.34
" This study was designed to determine the maximum tolerated dose (MTD), toxicity profile, and dose-limiting toxicity of belotecan in combination with cisplatin in patients with previously untreated extensive-stage disease small cell lung cancer (SCLC)."	( A phase I and pharmacologic study of belotecan in combination with cisplatin in patients with previously untreated extensive-stage disease small cell lung cancer. Bae, KS; Hong, JS; Kang, YK; Kim, SW; Lee, DH; Lee, JS; Suh, C, 2007)	0.34
"50 mg/m2/d on days 1 to 4 in combination with 60 mg/m2 cisplatin on day 1 every 3 weeks."	( A phase I and pharmacologic study of belotecan in combination with cisplatin in patients with previously untreated extensive-stage disease small cell lung cancer. Bae, KS; Hong, JS; Kang, YK; Kim, SW; Lee, DH; Lee, JS; Suh, C, 2007)	0.34
"This in vivo study was designed to determine the optimal doses and schedules of vandetanib, a dual epidermal growth factor receptor (EGFR)-vascular endothelial growth factor receptor tyrosine kinase inhibitor, in combination with irinotecan in a murine xenograft model of human colon cancer."	( Investigation of two dosing schedules of vandetanib (ZD6474), an inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling, in combination with irinotecan in a human colon cancer xenograft model. Ciardiello, F; Eckhardt, SG; Gustafson, DL; Henthorn, TK; Lockerbie, O; Long, M; Merz, A; Morrow, M; Serkova, NJ; Troiani, T, 2007)	0.34
"The greatest antitumor efficacy was observed in the groups receiving the highest dose of vandetanib given continuously (concurrent schedule), alone or in combination with irinotecan."	( Investigation of two dosing schedules of vandetanib (ZD6474), an inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling, in combination with irinotecan in a human colon cancer xenograft model. Ciardiello, F; Eckhardt, SG; Gustafson, DL; Henthorn, TK; Lockerbie, O; Long, M; Merz, A; Morrow, M; Serkova, NJ; Troiani, T, 2007)	0.34
"These data suggest that higher, sustained concentrations of vandetanib (versus intermittent), alone and in combination with irinotecan, result in optimal antitumor efficacy in this model and may have implications for the design of future clinical studies with this drug."	( Investigation of two dosing schedules of vandetanib (ZD6474), an inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling, in combination with irinotecan in a human colon cancer xenograft model. Ciardiello, F; Eckhardt, SG; Gustafson, DL; Henthorn, TK; Lockerbie, O; Long, M; Merz, A; Morrow, M; Serkova, NJ; Troiani, T, 2007)	0.34
"We conducted a phase I study to determine the recommended dose of selenomethionine (SLM) in combination with irinotecan that consistently results in a protective plasma selenium (Se) concentrations > 15 microM after 1 week of SLM loading."	( A Phase I and pharmacokinetic study of selenomethionine in combination with a fixed dose of irinotecan in solid tumors. Badmaev, V; Brady, W; Creaven, PJ; Fakih, MG; Pendyala, L; Prey, JD; Ross, ME; Rustum, YM; Smith, PF, 2008)	0.35
"Selenomethionine can be escalated safely to 7,200 mcg BID x 1 week followed by 7,200 mcg QD in combination with a standard dose of irinotecan."	( A Phase I and pharmacokinetic study of selenomethionine in combination with a fixed dose of irinotecan in solid tumors. Badmaev, V; Brady, W; Creaven, PJ; Fakih, MG; Pendyala, L; Prey, JD; Ross, ME; Rustum, YM; Smith, PF, 2008)	0.35
"To determine the recommended dose (RD) of EKB-569, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in combination with FOLFIRI chemotherapy in patients with metastatic colorectal cancer (mCRC)."	( Phase I pharmacokinetic/pharmacodynamic study of EKB-569, an irreversible inhibitor of the epidermal growth factor receptor tyrosine kinase, in combination with irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI) in first-line treatment of patients with Abbas, R; Andreu, J; Baselga, J; Casado, E; Cortes-Funes, H; Folprecht, G; Köhne, CH; Lejeune, C; Marimón, I; Paz-Ares, L; Quinn, S; Rojo, F; Salazar, R; Tabernero, J; Ubbelohde, U; Zacharchuk, C, 2008)	0.35
"The RD of EKB-569 is 25 mg/day when combined with FOLFIRI and results in complete EGFR inhibition."	( Phase I pharmacokinetic/pharmacodynamic study of EKB-569, an irreversible inhibitor of the epidermal growth factor receptor tyrosine kinase, in combination with irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI) in first-line treatment of patients with Abbas, R; Andreu, J; Baselga, J; Casado, E; Cortes-Funes, H; Folprecht, G; Köhne, CH; Lejeune, C; Marimón, I; Paz-Ares, L; Quinn, S; Rojo, F; Salazar, R; Tabernero, J; Ubbelohde, U; Zacharchuk, C, 2008)	0.35
" This study was conducted to investigate the advantages of NK012 over irinotecan hydrochloride (CPT-11) administered in combination with 5-fluorouracil (5FU)."	( Synergistic antitumor activity of the novel SN-38-incorporating polymeric micelles, NK012, combined with 5-fluorouracil in a mouse model of colorectal cancer, as compared with that of irinotecan plus 5-fluorouracil. Hamaguchi, T; Kano, Y; Kato, K; Koizumi, F; Matsumura, Y; Nakajima, TE; Shimada, Y; Shirao, K; Yamada, Y; Yasunaga, M, 2008)	0.35
" The patient was treated with S-1 combined with CPT-11."	( [An elderly patient with recurrent rectal cancer successfully responded to S-1 combined with CPT-11]. Doi, M; Egawa, T; Hayashi, S; Ito, Y; Kitano, M; Nagashima, A; Sekine, K; Shimizu, M; Yoshii, H, 2007)	0.34
"Oxaliplatin in combination with capecitabine prolongs survival in patients with metastatic colorectal cancer (mCRC)."	( Chronomodulated capecitabine in combination with short-time oxaliplatin: a Nordic phase II study of second-line therapy in patients with metastatic colorectal cancer after failure to irinotecan and 5-flourouracil. Balteskard, L; Berglund, A; Fokstuen, T; Ogreid, D; Pfeiffer, P; Ploen, J; Qvortrup, C; Starkhammar, H; Sørbye, H; Tveit, K; Yilmaz, M, 2008)	0.35
"To evaluate the efficacy and safety of irinotecan combined with UFT for untreated and pretreated metastatic colorectal cancer."	( Phase I/II study of 24-hour infusion of irinotecan combined with oral UFT for metastatic colorectal cancer. Ishikawa, K; Maeda, Y; Makuuchi, H; Murayama, C; Sadahiro, S; Suzuki, T; Yasuda, S, 2008)	0.35
"A 24-hour infusion of irinotecan combined with UFT is feasible and active for metastatic colorectal cancer."	( Phase I/II study of 24-hour infusion of irinotecan combined with oral UFT for metastatic colorectal cancer. Ishikawa, K; Maeda, Y; Makuuchi, H; Murayama, C; Sadahiro, S; Suzuki, T; Yasuda, S, 2008)	0.35
" Pharmacokinetic data suggested no drug-drug interaction."	( Safety of repeated administrations of ixabepilone given as a 3-hour infusion every other week in combination with irinotecan in patients with advanced malignancies. Boige, V; Cohen, M; Delbaldo, C; Faivre, S; Namouni, F; Pautier, P; Peck, R; Raymond, E; Soria, JC, 2008)	0.35
" We conducted a trial involving a 3-week schedule of irinotecan combined with cisplatin (IP) to validate the efficacy and toxicity of this regimen in patients with previously untreated extensive-stage SCLC (ES-SCLC)."	( Phase II study of a 3-week schedule of irinotecan combined with cisplatin in previously untreated extensive-stage small-cell lung cancer. Jung, SS; Kim, JO; Kim, SY; Lee, JE; Park, HS, 2007)	0.34
" Irinotecan 60 mg/m(2) was administered intravenously on days 1 and 8 in combination with cisplatin 60 mg/m(2) on day 1 every 21 days."	( Phase II study of a 3-week schedule of irinotecan combined with cisplatin in previously untreated extensive-stage small-cell lung cancer. Jung, SS; Kim, JO; Kim, SY; Lee, JE; Park, HS, 2007)	0.34
"Irinotecan toxicity is more likely in patients with Gilbert's syndrome carrying the UGT1A1*28 allele combined with reduced function UGT1A7 N129K/R131K and UGT1A7-57T/G SNP."	( Gilbert's Syndrome and irinotecan toxicity: combination with UDP-glucuronosyltransferase 1A7 variants increases risk. Erichsen, TJ; Heinemann, V; Lankisch, TO; Manns, MP; Schulz, C; Strassburg, CP; Zwingers, T, 2008)	0.35
"This study was designed to evaluate the in vitro cytotoxicity and in vivo efficacy of TRA-8, a mouse monoclonal antibody that binds to the DR5 death receptor for tumor necrosis factor-related apoptosis-inducing ligand (also called Apo2L), alone and in combination with CPT-11, against human colon cancer cells and xenografts."	( Treatment of human colon cancer xenografts with TRA-8 anti-death receptor 5 antibody alone or in combination with CPT-11. Buchsbaum, DJ; Kim, H; LoBuglio, AF; Nan, L; Oliver, PG; Wang, W; Zhou, T; Zinn, KR, 2008)	0.35
"DR5 expression was assessed on human colon cancer cell lines using flow cytometry, and cellular cytotoxicity after TRA-8 treatment, alone and in combination with SN-38, was determined by measuring cellular ATP levels."	( Treatment of human colon cancer xenografts with TRA-8 anti-death receptor 5 antibody alone or in combination with CPT-11. Buchsbaum, DJ; Kim, H; LoBuglio, AF; Nan, L; Oliver, PG; Wang, W; Zhou, T; Zinn, KR, 2008)	0.35
" Metronomic CPT-11 alone and combined with semaxinib significantly inhibits tumour growth in the absence of toxicity, which was accompanied by decreases in microvessel density and increases in TSP-1 gene expression in tumour tissues."	( Antiangiogenic and anticolorectal cancer effects of metronomic irinotecan chemotherapy alone and in combination with semaxinib. Allegrini, G; Bocci, G; Danesi, R; Del Tacca, M; Di Paolo, A; Falcone, A; Fanelli, G; Fioravanti, A; Kerbel, RS; Naccarato, AG; Orlandi, P; Viacava, P, 2008)	0.35
"Gefitinib at a dose of 250 mg daily in combination with weekly 5-fluorouracil at 2,000 mg/m(2) or gefitinib at a dose of 500 mg daily with 5-fluorouracil at 1,600 mg/m(2) plus oxaliplatin has an acceptable safety profile."	( Gefitinib in combination with oxaliplatin and 5-fluorouracil in irinotecan-refractory patients with colorectal cancer: a phase I study of the Arbeits gemeinschaft Internistische Onkologie (AIO). Bokemeyer, C; Hartmann, JT; Höhler, T; Holtmann, M; Kröning, H; Pintoffl, JP, 2008)	0.35
"We conducted a dose escalation study of Am in combination with CPT to determine the qualitative and quantitative toxicities and efficacy against extensive (ED) SCLC."	( Dose escalation study of amrubicin in combination with fixed-dose irinotecan in patients with extensive small-cell lung cancer. Oshita, F; Saito, H; Yamada, K, 2008)	0.35
" We then examined the antitumor effect of IAB-1 in combination with anticancer drugs against RCC."	( Significant antitumor activity of cationic multilamellar liposomes containing human interferon-beta gene in combination with 5-fluorouracil against human renal cell carcinoma. Abe, K; Fujiwara, J; Hayashi, I; Ishida, H; Kawauchi, A; Miki, T; Mizuno, M; Mizutani, Y; Nakanishi, H; Okada, K; Toiyama, D; Yamamoto, K; Yoshida, J, 2008)	0.35
" We evaluated TM in combination with irinotecan, 5-fluorouracil, and leucovorin (IFL)."	( A pilot trial of the anti-angiogenic copper lowering agent tetrathiomolybdate in combination with irinotecan, 5-flurouracil, and leucovorin for metastatic colorectal cancer. Brewer, GJ; Gartner, EM; Griffith, KA; Henja, GF; Merajver, SD; Pan, Q; Zalupski, MM, 2009)	0.35
" The FOLFIRI regimen consisted of irinotecan (180 mg/m(2); day 1) combined with leucovorin (200 mg/m(2)), followed by 5-fluorouracil (400 mg/m(2)) as a bolus and 600 mg/m(2) as a 22-h infusion on days 1 and 2 every 2 weeks."	( Irinotecan combined with 5-fluorouracil and leucovorin as second-line chemotherapy for metastatic or relapsed gastric cancer. Bang, YJ; Im, SA; Kim, DY; Kim, JH; Kim, TY; Lee, JS; Lee, KW; Lim, JH; Oh, DY; Seo, MD; Yi, HG, 2008)	0.35
" We treated the patient with S-1 combined with CPT-11."	( [Three cases with liver metastasis from gastric or colon cancer successfully treated with S-1 combined with CPT- 11]. Ishii, Y; Mado, K; Manmoto, J; Masuda, H; Mazaki, T; Okame, H; Suzuki, K; Takayama, T, 2008)	0.35
" The aim of this study was to determine the maximum tolerated dose of capecitabine, in substitution of 5-fluorouracil, combined with oxaliplatin and irinotecan and to evaluate the pharmacokinetics of the drugs."	( A dose finding and pharmacokinetic study of capecitabine in combination with oxaliplatin and irinotecan in metastatic colorectal cancer. Antonuzzo, A; Bocci, G; Bursi, S; Chiara, S; Del Tacca, M; Di Paolo, A; Falcone, A; Fornaro, L; Loupakis, F; Masi, G; Pfanner, E; Vasile, E, 2009)	0.35
"To evaluate the safety and efficacy of preoperative radiotherapy (RT) in combination with cetuximab, capecitabine, and irinotecan in patients with locally advanced rectal cancer."	( Cetuximab in combination with capecitabine, irinotecan, and radiotherapy for patients with locally advanced rectal cancer: results of a Phase II MARGIT trial. Barreto-Miranda, M; Dinter, D; Erben, P; Hochhaus, A; Hofheinz, RD; Horisberger, K; Kähler, G; Kienle, P; Mai, S; Post, S; Ströbel, P; Treschl, A; Wenz, F; Willeke, F; Woernle, C, 2009)	0.35
"Patients with rectal cancer (clinical stage T3/4 or N+) were scheduled to receive cetuximab (400 mg/m(2) Day 1, 250 mg/m(2) Days 8, 15, 22, 29) in combination with weekly irinotecan 40 mg/m(2) and capecitabine 500 mg/m(2) twice daily (Days 1-38)."	( Cetuximab in combination with capecitabine, irinotecan, and radiotherapy for patients with locally advanced rectal cancer: results of a Phase II MARGIT trial. Barreto-Miranda, M; Dinter, D; Erben, P; Hochhaus, A; Hofheinz, RD; Horisberger, K; Kähler, G; Kienle, P; Mai, S; Post, S; Ströbel, P; Treschl, A; Wenz, F; Willeke, F; Woernle, C, 2009)	0.35
"A total of 342 patients received irinotecan-based chemotherapy as second-line chemotherapy: FOLFIRI-3 [n = 109, irinotecan 100 mg/m(2) days 1 and 3 combined with leucovorin (LV) 400 mg/m(2) day 1 and 46-h continuous 5-fluorouracil (5-FU) 2000 mg/m(2)], FOLFIRI-1 (n = 112, irinotecan 180 mg/m(2) day 1 combined with LV 400 mg/m(2) day 1, 5-FU bolus 400 mg/m(2) and 46-h continuous 5-FU 2400 mg/m(2)) and other various irinotecan-based regimens (n = 121)."	( Efficacy of FOLFIRI-3 (irinotecan D1,D3 combined with LV5-FU) or other irinotecan-based regimens in oxaliplatin-pretreated metastatic colorectal cancer in the GERCOR OPTIMOX1 study. André, T; Bengrine-Lefevre, L; Bidard, FC; Cervantes, A; de Gramont, A; Figer, A; Lledo, G; Louvet, C; Mabro, M; Maindrault-Goebel, F; Tournigand, C, 2009)	0.35
" To determine the feasibility of S-1 combined with weekly irinotecan for patients with advanced NSCLC, we performed a phase I study to determine the maximum tolerated dose (MTD) and the recommended dose (RD) of irinotecan."	( Phase I study of daily S-1 combined with weekly irinotecan in patients with advanced non-small cell lung cancer. Honda, Y; Ishida, T; Ishimoto, O; Munakata, M; Sugawara, S, 2009)	0.35
" This phase I/II trial was performed to evaluate the efficacy and safety of continuous infusion of irinotecan combined with UFT plus leucovorin (LV) for metastatic colorectal cancer."	( Phase I/II study of twenty-four-hour infusion of irinotecan in combination with oral UFT plus leucovorin for metastatic colorectal cancer. Ishikawa, K; Maeda, Y; Makuuchi, H; Murayama, C; Sadahiro, S; Suzuki, T; Tanaka, A, 2009)	0.35
"A 24-hour infusion of irinotecan combined with UFT/LV is feasible and active for metastatic colorectal cancer."	( Phase I/II study of twenty-four-hour infusion of irinotecan in combination with oral UFT plus leucovorin for metastatic colorectal cancer. Ishikawa, K; Maeda, Y; Makuuchi, H; Murayama, C; Sadahiro, S; Suzuki, T; Tanaka, A, 2009)	0.35
"This study was designed to investigate the efficacy and safety of the epidermal growth factor receptor (EGFR) inhibitor cetuximab combined with irinotecan, folinic acid (FA) and two different doses of infusional 5-fluorouracil (5-FU) in the first-line treatment of EGFR-detectable metastatic colorectal cancer."	( Cetuximab in combination with irinotecan/5-fluorouracil/folinic acid (FOLFIRI) in the initial treatment of metastatic colorectal cancer: a multicentre two-part phase I/II study. Brezault, C; Cals, L; Husseini, F; Loos, AH; Nippgen, J; Peeters, M; Raoul, JL; Rougier, P; Van Laethem, JL, 2009)	0.35
"To investigate the advantages of treatment with the SN-38-incorporating polymeric micelles NK012 over CPT-11 in combination with cisplatin [cis-dichlorodiammineplatinum (II) (CDDP)] in mice bearing a small cell lung cancer xenograft in terms of antitumor activity and toxicity, particularly intestinal toxicity."	( Antitumor activity of NK012 combined with cisplatin against small cell lung cancer and intestinal mucosal changes in tumor-bearing mouse after treatment. Goto, K; Kenmotsu, H; Koga, Y; Kuroda, J; Matsumura, Y; Nagano, T; Nishimura, Y; Nishiwaki, Y; Sugino, T; Yasunaga, M, 2009)	0.35
"The chemotherapy of bevacizumab combined with irinotecan, fluorouracil and leucovorin results in better efficacy in patients with progressive metastatic colorectal cancer."	( [Clinical research of bevacizumab in combination with irinotecan, fluorouracil and leucovorin for advanced metastatic colorectal cancer]. Chen, B; Chen, JZ; Cui, F; Luo, RC; Wan, C; Zheng, H, 2009)	0.35
"Bevacizumab (Avastin) significantly improves overall survival (OS) and progression-free survival (PFS) when combined with first-line irinotecan (IFL) plus bolus 5-fluorouracil (5-FU) and leucovorin (LV) in patients with metastatic colorectal cancer (CRC)."	( Phase IV study of bevacizumab in combination with infusional fluorouracil, leucovorin and irinotecan (FOLFIRI) in first-line metastatic colorectal cancer. Ackland, S; Chiara, S; Clarke, S; Gapski, J; Langer, B; Mainwaring, P; Perez-Carrión, R; Sobrero, A; Young, S, 2009)	0.35
"1 months and is comparable to that observed in published phase III and community-based trials using first-line bevacizumab plus FOLFIRI, and to phase III trials using bevacizumab in combination with bolus 5-FU/LV plus IFL."	( Phase IV study of bevacizumab in combination with infusional fluorouracil, leucovorin and irinotecan (FOLFIRI) in first-line metastatic colorectal cancer. Ackland, S; Chiara, S; Clarke, S; Gapski, J; Langer, B; Mainwaring, P; Perez-Carrión, R; Sobrero, A; Young, S, 2009)	0.35
"Bevacizumab combined with first-line FOLFIRI is an effective and well-tolerated therapy option for patients with metastatic CRC."	( Phase IV study of bevacizumab in combination with infusional fluorouracil, leucovorin and irinotecan (FOLFIRI) in first-line metastatic colorectal cancer. Ackland, S; Chiara, S; Clarke, S; Gapski, J; Langer, B; Mainwaring, P; Perez-Carrión, R; Sobrero, A; Young, S, 2009)	0.35
"Lung cancer tissue and normal lung tissue obtained from 8 patients who underwent operation were cultured and treated with Apo2L/TRAIL alone and in combination with cisplatin and the topoisomerase I inhibitor camptothecin for different periods."	( Cytotoxic effects of camptothecin and cisplatin combined with tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) in a model of primary culture of non-small cell lung cancer. Frese, S; Frese-Schaper, M; Gugger, M; Schmid, RA; Schüller, A, 2009)	0.86
"To determine the efficacy and tolerability of capecitabine combined with oxaliplatin (CAPOX) or irinotecan (CAPIRI) as first-line treatment in patients with advanced/metastatic colorectal cancer aged > or =70 years."	( Capecitabine in combination with oxaliplatin or irinotecan in elderly patients with advanced colorectal cancer: results of a randomized phase II study. Bordonaro, R; Caputo, G; Cordio, S; Manzione, L; Novello, G; Reggiardo, G; Rosati, G, 2010)	0.36
"We evaluated the efficacy of bevacizumab, alone and in combination with irinotecan, in patients with recurrent glioblastoma in a phase II, multicenter, open-label, noncomparative trial."	( Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. Abrey, LE; Cloughesy, T; Friedman, HS; Huang, J; Jensen, R; Mikkelsen, T; Nicholas, MK; Paleologos, N; Prados, MD; Schiff, D; Vredenburgh, J; Wen, PY; Yung, WK; Zheng, M, 2009)	0.35
"One hundred sixty-seven patients were randomly assigned to receive bevacizumab 10 mg/kg alone or in combination with irinotecan 340 mg/m(2) or 125 mg/m(2) (with or without concomitant enzyme-inducing antiepileptic drugs, respectively) once every 2 weeks."	( Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. Abrey, LE; Cloughesy, T; Friedman, HS; Huang, J; Jensen, R; Mikkelsen, T; Nicholas, MK; Paleologos, N; Prados, MD; Schiff, D; Vredenburgh, J; Wen, PY; Yung, WK; Zheng, M, 2009)	0.35
"Bevacizumab, alone or in combination with irinotecan, was well tolerated and active in recurrent glioblastoma."	( Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. Abrey, LE; Cloughesy, T; Friedman, HS; Huang, J; Jensen, R; Mikkelsen, T; Nicholas, MK; Paleologos, N; Prados, MD; Schiff, D; Vredenburgh, J; Wen, PY; Yung, WK; Zheng, M, 2009)	0.35
"To evaluate the outcomes of patients with unresectable massive primary liver cancer (PLC) receiving three-dimensional conformal radiotherapy (3-DCRT) combined with transcatheter arterial chemoembolization (TACE)."	( [Three-dimensional conformal radiotherapy combined with transcatheter arterial chemoembolization for massive primary liver cancer]. Chen, LH; Guan, J; Li, QS; Sun, HW; Wei, CJ; Zheng, XK, 2009)	0.35
"From January 2001 to December 2004, 84 patients with unresectable massive PLC (tumor size> or =10 cm) received 3-DCRT combined with TACE, including 49 cases in UICC/AJCC T(3) stage and 35 cases in T(4) stages."	( [Three-dimensional conformal radiotherapy combined with transcatheter arterial chemoembolization for massive primary liver cancer]. Chen, LH; Guan, J; Li, QS; Sun, HW; Wei, CJ; Zheng, XK, 2009)	0.35
"3-DCRT combined with TACE has definite therapeutic effect on advanced massive PLC, and Child-Pugh grade is an independent prognostic factor in such cases."	( [Three-dimensional conformal radiotherapy combined with transcatheter arterial chemoembolization for massive primary liver cancer]. Chen, LH; Guan, J; Li, QS; Sun, HW; Wei, CJ; Zheng, XK, 2009)	0.35
" We explored the efficacy and toxicity of gemcitabine administered at a fixed dose rate or in combination with cisplatin, docetaxel, or irinotecan in a multi-institutional, randomized, phase II study."	( Randomized phase II study of gemcitabine administered at a fixed dose rate or in combination with cisplatin, docetaxel, or irinotecan in patients with metastatic pancreatic cancer: CALGB 89904. Cusnir, M; Enzinger, PC; Goldberg, RM; Gorsch, SM; Hollis, DR; Kindler, HL; Kulke, MH; Mayer, RJ; Niedzwiecki, D; Tempero, MA, 2009)	0.35
" The recommended phase II dose of flavopiridol was 45 mg/m in combination with irinotecan and gemcitabine every 2 weeks."	( A phase I study of flavopiridol in combination with gemcitabine and irinotecan in patients with metastatic cancer. Chyi Lee, F; Fekrazad, HM; Rabinowitz, I; Royce, M; Smith, HO; Verschraegen, CF, 2010)	0.36
"The every 2 week dosing is well tolerated with a phase II recommended dose of 45 mg/m of flavopiridol in combination with irinotecan (80 mg/m) and gemcitabine (800 mg/m)."	( A phase I study of flavopiridol in combination with gemcitabine and irinotecan in patients with metastatic cancer. Chyi Lee, F; Fekrazad, HM; Rabinowitz, I; Royce, M; Smith, HO; Verschraegen, CF, 2010)	0.36
" Selected cardiac glycosides were tested in combination with four clinically relevant cytotoxic drugs (5-fluorouracil, oxaliplatin, cisplatin, irinotecan)."	( Cytotoxic effects of cardiac glycosides in colon cancer cells, alone and in combination with standard chemotherapeutic drugs. Bohlin, L; Felth, J; Fryknäs, M; Gullbo, J; Lindskog, M; Rickardson, L; Rosén, J; Wickström, M, 2009)	0.35
"Studies showed that cetuximab combined with chemotherapy was effective on advanced colorectal cancer (ACRC) in recent years, however, few reports based on large case cohort are available in China."	( [Efficacy of cetuximab combined with chemotherapy on advanced colorectal cancer: a report of 53 cases]. Chen, XX; Guo, GF; Hu, PL; Jiang, WQ; Liu, MZ; Qiu, HJ; Xia, LP; Zhang, B; Zhou, FF, 2009)	0.35
"Clinical data of 53 patients with ACRC, treated with cetuximab combined with chemotherapy in Sun Yat-sen Cancer Center from March 2005 to April 2008, were analyzed for short-term efficacy and safety."	( [Efficacy of cetuximab combined with chemotherapy on advanced colorectal cancer: a report of 53 cases]. Chen, XX; Guo, GF; Hu, PL; Jiang, WQ; Liu, MZ; Qiu, HJ; Xia, LP; Zhang, B; Zhou, FF, 2009)	0.35
"Cetuximab combined with chemotherapy can achieve relatively high disease control rate for ACRC patients, with less adverse events."	( [Efficacy of cetuximab combined with chemotherapy on advanced colorectal cancer: a report of 53 cases]. Chen, XX; Guo, GF; Hu, PL; Jiang, WQ; Liu, MZ; Qiu, HJ; Xia, LP; Zhang, B; Zhou, FF, 2009)	0.35
" Under hypoxic conditions, the expression of HIF-1alpha and VEGF increased as time accumulated, Bevacizumab combined with SN-38 almost completely inhibited the expression of HIF-1alpha and VEGF."	( [Combination with SN-38 on human colon cancer LoVo cells]. Song, ST; Wang, Y; Xu, JM; Xu, QZ; Zhou, PK, 2009)	0.35
"We studied the safety and tolerability of telatinib, an orally available, small-molecule tyrosine kinase inhibitor of the vascular endothelial growth factor receptor (VEGFR-2/VEGFR-3), platelet-derived growth factor receptor beta, and c-Kit in combination with capecitabine and irinotecan."	( Phase I evaluation of telatinib, a vascular endothelial growth factor receptor tyrosine kinase inhibitor, in combination with irinotecan and capecitabine in patients with advanced solid tumors. Brendel, E; Laferriere, N; Langenberg, MH; Mergui-Roelvink, M; Roodhart, JM; Schellens, JH; van der Sar, J; Verheul, HM; Voest, EE; Witteveen, PO, 2010)	0.36
"Continuous administration of 900 mg telatinib twice daily can be safely combined with irinotecan (180 mg/m(2)) and capecitabine (1,000 mg/m(2) twice daily, day 1-14) and is the recommended schedule for further phase II studies."	( Phase I evaluation of telatinib, a vascular endothelial growth factor receptor tyrosine kinase inhibitor, in combination with irinotecan and capecitabine in patients with advanced solid tumors. Brendel, E; Laferriere, N; Langenberg, MH; Mergui-Roelvink, M; Roodhart, JM; Schellens, JH; van der Sar, J; Verheul, HM; Voest, EE; Witteveen, PO, 2010)	0.36
" To evaluate further the potential therapeutic impact of metronomic chemotherapy for ovarian cancer, we developed a preclinical model of advanced human ovarian cancer and tested various low-dose metronomic chemotherapy regimens alone or in concurrent combination with an antiangiogenic drug, pazopanib."	( Potent preclinical impact of metronomic low-dose oral topotecan combined with the antiangiogenic drug pazopanib for the treatment of ovarian cancer. Cruz-Munoz, W; Hashimoto, K; Kerbel, RS; Kumar, R; Man, S; Tang, T; Xu, P, 2010)	0.36
"To evaluate the short-term efficacy and toxicity of endostar in combination with XELIRI as the second-line treatment for advanced colorectal cancer."	( [Short-term therapeutic effect and safety of endostar combined with XELIRI regimen in the treatment of advanced colorectal cancer]. Liao, WJ; Luo, RC; Shen, P; Shi, M; Wu, Wy, 2010)	0.36
"Endostar combined with XELIRI is effective and safe as the second-line treatment for advanced colorectal cancer, and further clinical investigation is warranted."	( [Short-term therapeutic effect and safety of endostar combined with XELIRI regimen in the treatment of advanced colorectal cancer]. Liao, WJ; Luo, RC; Shen, P; Shi, M; Wu, Wy, 2010)	0.36
" In the current study, the authors examined the antitumor effect of NK012 in combination with Bv against human lung cancer."	( The antitumor activity of NK012, an SN-38-incorporating micelle, in combination with bevacizumab against lung cancer xenografts. Goto, K; Kenmotsu, H; Koga, Y; Kuroda, J; Matsumura, Y; Nagano, T; Nishiwaki, Y; Takahashi, A; Yasunaga, M, 2010)	0.36
"Nude mice bearing lung adenocarcinoma (PC-14 or A549 xenografts) were administered NK012 at SN-38-equivalent doses of 5 mg/kg or 30 mg/kg in combination with or without Bv at 5 mg/kg."	( The antitumor activity of NK012, an SN-38-incorporating micelle, in combination with bevacizumab against lung cancer xenografts. Goto, K; Kenmotsu, H; Koga, Y; Kuroda, J; Matsumura, Y; Nagano, T; Nishiwaki, Y; Takahashi, A; Yasunaga, M, 2010)	0.36
"In this study, significant antitumor activity was noted with NK012 in combination with Bv against lung cancer cells."	( The antitumor activity of NK012, an SN-38-incorporating micelle, in combination with bevacizumab against lung cancer xenografts. Goto, K; Kenmotsu, H; Koga, Y; Kuroda, J; Matsumura, Y; Nagano, T; Nishiwaki, Y; Takahashi, A; Yasunaga, M, 2010)	0.36
" Irinotecan showed genotoxic activity in combination with the new platinum(II) derivatives in cancer cells."	( Genotoxic effects of irinotecan combined with the novel platinum(II) complexes in human cancer cells. Kalinowska-Lis, U; Kontek, R; Marciniak, B; Matlawska-Wasowska, K, 2010)	0.36
"This trial aimed to define a recommended safe dose (RSD) of weekly paclitaxel and irinotecan combined with carboplatin in patients with advanced cancer."	( Phase I trial of weekly irinotecan and paclitaxel combined with carboplatin in patients with advanced cancer: a Hellenic Cooperative Oncology Group Study. Briasoulis, E; Fountzilas, G; Golfinopoulos, V; Karina, M; Papakostas, P; Pavlidis, N, 2010)	0.36
"Generally, there was little difference in CPT-11 pharmacokinetics when combined with CTX in the 11 enrolled patients."	( Pharmacokinetics of irinotecan in combination with biweekly cetuximab in patients with advanced colorectal cancer. Czejka, M; Farkouh, A; Gruenberger, B; Kiss, A; Schueller, J, 2010)	0.36
" We investigated the safety and pharmacokinetics of sunitinib in combination with irinotecan in patients with advanced, refractory solid tumours."	( A phase I, dose-finding study of sunitinib in combination with irinotecan in patients with advanced solid tumours. Armand, JP; Boven, E; Brega, NM; Countouriotis, AM; Hartog, V; Massard, C; Ruiz-Garcia, A; Soria, JC; Tillier, C, 2010)	0.36
" Paired observations of pharmacokinetic parameter values of sunitinib and irinotecan alone vs the combination did not reveal significant drug-drug interactions."	( A phase I, dose-finding study of sunitinib in combination with irinotecan in patients with advanced solid tumours. Armand, JP; Boven, E; Brega, NM; Countouriotis, AM; Hartog, V; Massard, C; Ruiz-Garcia, A; Soria, JC; Tillier, C, 2010)	0.36
"Capecitabine is an oral fluoropyrimidine that is shown to have similar efficacy to 5-fluorouracil (5-FU) when used both alone and in combination with oxaliplatin in the treatment of colorectal cancer (CRC)."	( Differences in efficacy and safety between capecitabine and infusional 5-fluorouracil when combined with irinotecan for the treatment of metastatic colorectal cancer. Aliberti, C; Chiriatti, A; Fiorentini, G; Licitra, S; Montagnani, F, 2010)	0.36
" Hazard ratios for progression and death were combined with an inverse variance method based on logarithmic conversion."	( Differences in efficacy and safety between capecitabine and infusional 5-fluorouracil when combined with irinotecan for the treatment of metastatic colorectal cancer. Aliberti, C; Chiriatti, A; Fiorentini, G; Licitra, S; Montagnani, F, 2010)	0.36
"Superiority of camptothecin regimens over etoposide-both combined with platinum analogs-in extensive disease small cell lung cancer has been a matter of debate with contradictory findings in randomized trials."	( Camptothecins compared with etoposide in combination with platinum analog in extensive stage small cell lung cancer: systematic review with meta-analysis. dos Santos, LV; Lima, CS; Lima, JP; Sasse, AD; Sasse, EC, 2010)	2.16
" The aim of this study was to evaluate the efficacy and safety of this regimen in combination with bevacizumab (BV), as first-line treatment for mCRC."	( Bevacizumab in combination with biweekly capecitabine and irinotecan, as first-line treatment for patients with metastatic colorectal cancer. Alvarez-Suarez, S; García-Alfonso, P; Jerez-Gilarranz, Y; Khosravi, P; Martin, M; Muñoz-Martin, AJ; Riesco-Martinez, M, 2010)	0.36
"Bevacizumab combined with biweekly XELIRI is a highly active first-line regimen for mCRC treatment, showing encouraging PFS, ORR and OS with a good tolerability."	( Bevacizumab in combination with biweekly capecitabine and irinotecan, as first-line treatment for patients with metastatic colorectal cancer. Alvarez-Suarez, S; García-Alfonso, P; Jerez-Gilarranz, Y; Khosravi, P; Martin, M; Muñoz-Martin, AJ; Riesco-Martinez, M, 2010)	0.36
" We investigated the anti-tumor effects of CG2 (an HDACI) in combination with irinotecan, 5-FU, or oxaliplatin."	( Effects of the HDAC inhibitor CG2 in combination with irinotecan, 5-fluorouracil, or oxaliplatin on HCT116 colon cancer cells and xenografts. Cho, DH; Hong, YS; Jin, DH; Jung, KA; Kim, JC; Kim, SM; Kim, TW; Lee, JS; Na, YS; Ro, S; Ryu, MH; Yang, SJ, 2010)	0.36
" We conducted this study to investigate its efficacy and safety when combined with chemotherapy in patients with advanced solid tumors."	( Efficacy and safety of endostar combined with chemotherapy in patients with advanced solid tumors. Huang, XE; Jiang, Y; Li, Y; Xiang, J; Yan, PW, 2010)	0.36
"5 mg/m2 /day as an intravenous infusion for more than 7 days, in combination with chemotherapy."	( Efficacy and safety of endostar combined with chemotherapy in patients with advanced solid tumors. Huang, XE; Jiang, Y; Li, Y; Xiang, J; Yan, PW, 2010)	0.36
"Our study revealed that toxicity of Endostar combined with chemotherapy in the treatment of solid tumors was tolerable with moderate efficacy."	( Efficacy and safety of endostar combined with chemotherapy in patients with advanced solid tumors. Huang, XE; Jiang, Y; Li, Y; Xiang, J; Yan, PW, 2010)	0.36
"To study the efficacy and safety of cetuximab combined with chemotherapy for patients with advanced colorectal cancer (ACRC) and unclear K-ras status."	( [Efficacy of cetuximab combined with chemotherapy for patients with advanced colorectal cancer and unclear K-ras status]. Guo, GF; Jiang, WQ; Qiu, HJ; Wang, F; Xia, LP; Xu, RH; Zhang, B; Zhou, FF, 2010)	0.36
"Clinical data of 102 ACRC patients, treated by cetuximab combined with chemotherapy in Sun Yat-sen Cancer Center from March 2005 to December 2008, were collected."	( [Efficacy of cetuximab combined with chemotherapy for patients with advanced colorectal cancer and unclear K-ras status]. Guo, GF; Jiang, WQ; Qiu, HJ; Wang, F; Xia, LP; Xu, RH; Zhang, B; Zhou, FF, 2010)	0.36
"Patients with advanced colorectal cancer and unclear K-ras treated by cetuximab combined with chemotherapy have good ORR and OS, and the regimen is safe with less adverse events for them."	( [Efficacy of cetuximab combined with chemotherapy for patients with advanced colorectal cancer and unclear K-ras status]. Guo, GF; Jiang, WQ; Qiu, HJ; Wang, F; Xia, LP; Xu, RH; Zhang, B; Zhou, FF, 2010)	0.36
"To compare clinical efficacy and toxicity of irinotecan combined with 5-fluorouracil and leucovorin with those of oxaliplatin combined with 5-fluorouracil and leucovorin as first-line therapy for advanced colorectal cancer."	( Irinotecan or oxaliplatin combined with 5-fluorouracil and leucovorin as first-line therapy for advanced colorectal cancer: a meta-analysis. Hou, SH; Li, YP; Liang, XB; Wang, LC; Yang, J; Zhang, X, 2010)	0.36
"Literature search was performed by keywords "irinotecan", "oxaliplatin" and "colorectal cancer" on all randomized controlled trails reported on irinotecan versus oxaliplatin combined with 5-fluorouracil and leucovorin as first-line therapy for advanced colorectal cancer in MEDLINE, OVID, Springer, Cochrane Controlled Trials Register (CCTR) and CBMdisc (Chinese Biology and Medicine disc) before January 2010."	( Irinotecan or oxaliplatin combined with 5-fluorouracil and leucovorin as first-line therapy for advanced colorectal cancer: a meta-analysis. Hou, SH; Li, YP; Liang, XB; Wang, LC; Yang, J; Zhang, X, 2010)	0.36
"Both irinotecan and oxaliplatin combined with 5-fluorouracil and leucovorin were effective in the first-line therapy of advanced colorectal cancer."	( Irinotecan or oxaliplatin combined with 5-fluorouracil and leucovorin as first-line therapy for advanced colorectal cancer: a meta-analysis. Hou, SH; Li, YP; Liang, XB; Wang, LC; Yang, J; Zhang, X, 2010)	0.36
"We conducted a Phase I clinical trial to evaluate the safety, tolerability, and pharmacokinetics (PK) of CKD-732 [6-O-(4-dimethylaminoethoxy) cinnamoyl fumagillol hemioxalate] in combination with capecitabine and oxaliplatin (XELOX) in nine metastatic colorectal cancer patients who had progressed on irinotecan-based chemotherapy."	( A Phase Ib pharmacokinetic study of the anti-angiogenic agent CKD-732 used in combination with capecitabine and oxaliplatin (XELOX) in metastatic colorectal cancer patients who progressed on irinotecan-based chemotherapy. Ahn, JB; Chung, HC; Hong, YS; Kim, C; Kim, DH; Kim, HR; Kim, TW; Lee, YJ; Park, KS; Rha, SY; Roh, JK; Shin, SJ, 2012)	0.38
" The maximum tolerated dose was 10 mg/m(2)/d, and the clinically recommended dose was 5 mg/m(2)/d for CKD-732 in combination with XELOX."	( A Phase Ib pharmacokinetic study of the anti-angiogenic agent CKD-732 used in combination with capecitabine and oxaliplatin (XELOX) in metastatic colorectal cancer patients who progressed on irinotecan-based chemotherapy. Ahn, JB; Chung, HC; Hong, YS; Kim, C; Kim, DH; Kim, HR; Kim, TW; Lee, YJ; Park, KS; Rha, SY; Roh, JK; Shin, SJ, 2012)	0.38
"The Phase II recommended dose of CKD-732 was determined to be 5 mg/m(2)/d, and this dose was safely combined with a conventional dose of capecitabine and oxaliplatin in this patient population."	( A Phase Ib pharmacokinetic study of the anti-angiogenic agent CKD-732 used in combination with capecitabine and oxaliplatin (XELOX) in metastatic colorectal cancer patients who progressed on irinotecan-based chemotherapy. Ahn, JB; Chung, HC; Hong, YS; Kim, C; Kim, DH; Kim, HR; Kim, TW; Lee, YJ; Park, KS; Rha, SY; Roh, JK; Shin, SJ, 2012)	0.38
" We examined the efficacy of metronomic irinotecan combined with low-intensity ultrasound (US) in human uterine sarcoma and evaluated its antiangiogenesis mechanism by measuring the circulating endothelial progenitor cells (CEP), a surrogate marker of angiogenesis."	( Metronomic irinotecan chemotherapy combined with ultrasound irradiation for a human uterine sarcoma xenograft. Choijamts, B; Emoto, M; Kawarabayashi, T; Miyamoto, S; Naganuma, Y; Nakajima, K; Tachibana, K, 2011)	0.37
" Neither were there significant differences in the absolute nadir and percentage decrease of WBC and ANC, nor on the incidence and severity of neutropenia, febrile neutropenia, diarrhoea, nausea and vomiting when irinotecan was combined with omeprazole."	( Effect of omeprazole on the pharmacokinetics and toxicities of irinotecan in cancer patients: a prospective cross-over drug-drug interaction study. de Bruijn, P; de Jong, FA; Konings, IR; Lam, MH; Loos, WJ; Mathijssen, RH; van der Bol, JM; van Meerten, E; Verweij, J; Wiemer, EA, 2011)	0.37
"Interstitial lung disease in patients with colorectal cancer during chemotherapy combined with bevacizumab is rare."	( Interstitial lung disease during chemotherapy combined with oxaliplatin and/or bevacizumab in advanced colorectal cancer patients. Furushima, K; Ishihara, T; Katou, Y; Tanai, C; Tanaka, Y; Usui, K, 2011)	0.37
"The MTD of sunitinib combined with FOLFIRI in chemotherapy-naive mCRC was 37."	( A phase I study of sunitinib in combination with FOLFIRI in patients with untreated metastatic colorectal cancer. Aranda, E; Carrato, A; Chau, I; Countouriotis, AM; Cunningham, D; Guillen-Ponce, C; Iveson, TJ; Ramos, FJ; Ruiz-Garcia, A; Saunders, MP; Starling, N; Tabernero, J; Tursi, JM; Vázquez-Mazón, F; Wei, G, 2012)	0.38
"To demonstrate the antiproliferative and pro-apoptotic activity of the novel pyrazolopyrimidine derivative multiple tyrosine kinase inhibitor CLM3, alone and in combination with SN-38 (the active metabolite of irinotecan), on endothelial and tumor cells and to show its mechanism of action."	( Antiproliferative and proapoptotic activity of CLM3, a novel multiple tyrosine kinase inhibitor, alone and in combination with SN-38 on endothelial and cancer cells. Antonelli, A; Berti, P; Bocci, G; Canu, B; Cosconati, S; Da Settimo, F; Danesi, R; Di Desidero, T; Fioravanti, A; Frati, R; La Motta, C; Miccoli, P; Mugnaini, L; Orlandi, P; Sartini, S, 2011)	0.37
"Proliferation and apoptotic assays were performed on microvascular endothelial (HMVEC-d) and lung (A549) and thyroid cancer (8305C, TT) cell lines exposed to CLM3 and to the simultaneous combination with SN38 for 72h."	( Antiproliferative and proapoptotic activity of CLM3, a novel multiple tyrosine kinase inhibitor, alone and in combination with SN-38 on endothelial and cancer cells. Antonelli, A; Berti, P; Bocci, G; Canu, B; Cosconati, S; Da Settimo, F; Danesi, R; Di Desidero, T; Fioravanti, A; Frati, R; La Motta, C; Miccoli, P; Mugnaini, L; Orlandi, P; Sartini, S, 2011)	0.37
"The pyrazolopyrimidine derivative CLM3 demonstrated a highly significant and promising antiproliferative and proapoptotic activity, alone and in combination with SN-38, for activated endothelial and cancer cells."	( Antiproliferative and proapoptotic activity of CLM3, a novel multiple tyrosine kinase inhibitor, alone and in combination with SN-38 on endothelial and cancer cells. Antonelli, A; Berti, P; Bocci, G; Canu, B; Cosconati, S; Da Settimo, F; Danesi, R; Di Desidero, T; Fioravanti, A; Frati, R; La Motta, C; Miccoli, P; Mugnaini, L; Orlandi, P; Sartini, S, 2011)	0.37
" This phase II study was designed to evaluate the toxicity and efficacy of belotecan combined with carboplatin in patients with recurrent epithelial ovarian cancer (EOC)."	( Phase II study of belotecan, a camptothecin analogue, in combination with carboplatin for the treatment of recurrent ovarian cancer. Bae, DS; Choi, CH; Kim, BG; Kim, MK; Kim, TJ; Lee, JH; Lee, JW; Lee, YY; Park, HS; Song, TJ, 2011)	0.66
"The newly developed topoisomerase I inhibitor belotecan (CKD-602) combined with carboplatin is a well-tolerated regimen with activity in recurrent EOC."	( Phase II study of belotecan, a camptothecin analogue, in combination with carboplatin for the treatment of recurrent ovarian cancer. Bae, DS; Choi, CH; Kim, BG; Kim, MK; Kim, TJ; Lee, JH; Lee, JW; Lee, YY; Park, HS; Song, TJ, 2011)	0.66
" Treatment regimen: irinotecan (80 mg/m²) as 1-h infusion followed by 5-FU (2000 mg/m²) combined with FA (500 mg/m²) as 24-h infusion (d1, 8, 15, 22, 29, 36, qd 57)."	( Palliative first-line therapy with weekly high-dose 5-fluorouracil and sodium folinic acid as a 24-hour infusion (AIO regimen) combined with weekly irinotecan in patients with metastatic adenocarcinoma of the stomach or esophagogastric junction followed b Albrecht, H; Boxberger, F; Busse, D; Golcher, H; Hahn, EG; Hohenberger, W; Janka, R; Konturek, PC; Koucky, K; Männlein, G; Neurath, MF; Ostermeier, N; Reulbach, U; Schildberg, C; Siebler, J; Wein, A; Wolff, K, 2011)	0.37
"Patients with metastatic colorectal cancer who had progressed on therapy with 5-FU, oxaliplatin and irinotecan in the first and second line setting and on the combination of irinotecan and cetuximab in third line setting independent of their KRAS mutation status, were treated with irinotecan and cetuximab combined with bevacizumab in a dosage of 5 mg/kg."	( Bevacizumab in combination with cetuximab and irinotecan after failure of cetuximab and irinotecan in patients with metastatic colorectal cancer. Bjerregaard, JK; Fromm, AL; Hoegdall, E; Jensen, BV; Jørgensen, TL; Larsen, FO; Nielsen, D; Pfeiffer, P; Qvortrup, C; Skougaard, K; Vistisen, K, 2011)	0.37
" Three courses of chemotherapy combined with irinotecan hydrochloride (CPT-11) and cisplatin (CDDP)(CPT-P) remarkably reduced the volume of the primary tumor and disseminated foci."	( [Successful optimal debulking surgery following chemotherapy combined with irinotecan hydrochloride and cisplatin for advanced clear cell carcinoma of the ovary]. Futagami, M; Hakamada, K; Hirakawa, H; Mizunuma, H; Yokoyama, Y, 2011)	0.37
"To observe and compare the response rate and toxicity of irinotecan or oxaliplatin combined with capecitabine in the treatment of advanced gastric cancer."	( [Comparison between the effects of irinotecan or oxaliplatin combined with capecitabine in the treatment of advanced gastric cancer]. Chen, DY; Qi, Q; Zhao, WY, 2011)	0.37
"The therapeutic effects of irinotecan or oxaliplatin combined with capecitabine in the treatment of advanced gastric cancer are good and comparable, and their toxicities are tolerable."	( [Comparison between the effects of irinotecan or oxaliplatin combined with capecitabine in the treatment of advanced gastric cancer]. Chen, DY; Qi, Q; Zhao, WY, 2011)	0.37
"To test the hypothesis that co-delivery of synergistic drug combinations in the same liposome provides a better anti-tumor effect than the drugs administered in separate liposomes, fluoroorotic acid (FOA) alone and in combination with irinotecan (IRN) were encapsulated in liposomes and evaluated for their anti-tumor activity in the C26 colon carcinoma mouse model."	( Anti-tumor activity of liposome encapsulated fluoroorotic acid as a single agent and in combination with liposome irinotecan. Jerger, K; Kieler-Ferguson, HM; Riviere, K; Szoka, FC, 2011)	0.37
"The most commonly used schedules are 5-FU in combination with CDDP with or without epirubicin (ECF) or docetaxel (TCF) in treatment of MGA patients (pts), independently of HER status."	( Efficacy of irinotecan in combination with 5-fluorouracil (FOLFIRI) for metastatic gastric or gastroesophageal junction adenocarcinomas (MGA) treatment. Abbas, F; Adenis, A; Afchain, P; Aparicio, T; Bécouarn, Y; Bouché, O; Desseigne, F; Dorval, E; Edeline, J; Guimbaud, R; Kramar, A; Mitry, E; Romano, O; Samalin, E; Thézenas, S; Ychou, M, 2011)	0.37
" To the best of our knowledge, cases of EGC combined with metachronous osteosclerotic multiple bone and bone marrow metastases that respond to chemoradiotherapy are very rare."	( Early gastric cancer combined with multiple metachronous osteosclerotic bone and bone marrow metastases that responded to chemoradiotherapy. Chiba, F; Kiyozaki, H; Konishi, F; Saito, M; Shuto, C; Takata, O; Yamada, S; Yoshida, T, 2011)	0.37
"To retrospectively evaluate the efficacy and tolerability of mitomycin-C (MMC) in combination with fluoropyrimidines as salvage 3rd -or 4th-line therapy in metastatic colorectal cancer (MCRC) patients."	( Mitomycin-C in combination with fluoropyrimidines in the treatment of metastatic colorectal cancer after oxaliplatin and irinotecan failure. Alkis, N; Benekli, M; Demirci, U; Gumus, M; Isikdogan, A; Kaplan, MA; Koca, D; Ozdemir, NY; Sevinc, A; Uncu, D; Unek, T; Yetisyigit, T; Yilmaz, U, )	0.13
"MMC in combination with fluoropyrimidines is safe and active in heavily-pretreated MCRC patients."	( Mitomycin-C in combination with fluoropyrimidines in the treatment of metastatic colorectal cancer after oxaliplatin and irinotecan failure. Alkis, N; Benekli, M; Demirci, U; Gumus, M; Isikdogan, A; Kaplan, MA; Koca, D; Ozdemir, NY; Sevinc, A; Uncu, D; Unek, T; Yetisyigit, T; Yilmaz, U, )	0.13
"To evaluate the safety and efficacy of trsatuzumab (Herceptin) combined with FOLFIRI regimen (irinotecan plus 5-FU/LV) in the treatment of HER2-positive advanced gastric cancer."	( [Efficacy of trsatuzumab (Herceptin) combined with FOLFIRI regimen in the treatment of HER2-positive advanced gastric cancer]. Chen, QQ; Gao, XP; Li, W; Pan, SY; Sun, J, 2011)	0.37
"Trsatuzumab combined with FOLFIRI regimen is effective, safe and well tolerated for treatment of HER2-positive advanced gastric cancer."	( [Efficacy of trsatuzumab (Herceptin) combined with FOLFIRI regimen in the treatment of HER2-positive advanced gastric cancer]. Chen, QQ; Gao, XP; Li, W; Pan, SY; Sun, J, 2011)	0.37
" Vorinostat was combined with bevacizumab and CPT-11 and was escalated using a standard 3 + 3 design."	( Phase I trial of vorinostat combined with bevacizumab and CPT-11 in recurrent glioblastoma. Brem, S; Chinnaiyan, P; Chowdhary, S; Kahali, S; Murtagh, R; Pan, E; Potthast, L; Prabhu, A; Rojiani, A; Sarcar, B; Tsai, YY; Yu, HM, 2012)	0.38
" Dbait has already been shown to be effective in combination with radiotherapy."	( Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer. Berger, F; Biau, J; Bousquet, G; Devun, F; Dutreix, M; Herbette, A; Robine, S; Roulin, C; Sun, JS, 2012)	0.38
"We assessed DNA repair efficiency over time, in vitro, in human colon adenocarcinoma HT-29 (wild-type KRAS) and HCT-116 (mutated KRAS) cell lines treated with Dbait in combination with 5-fluorouracil and/or camptothecin."	( Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer. Berger, F; Biau, J; Bousquet, G; Devun, F; Dutreix, M; Herbette, A; Robine, S; Roulin, C; Sun, JS, 2012)	0.57
" Possible further antitumor efficacy of lower-dose and longer-term CPT-11 combined with simultaneous low-dose celecoxib was investigated for chemosensitive TNB9 and multi-drug resistant TS-N-2nu neuroblastoma xenografts."	( Enhanced antitumor effect of lower-dose and longer-term CPT-11 treatment in combination with low-dose celecoxib against neuroblastoma xenografts. Fukushima, T; Kaneko, M; Kaneko, S, 2013)	0.39
"Our findings demonstrate that lower-dose and longer-term CPT-11 treatment in combination with simultaneous low-dose celecoxib enhances antitumor activity and can successfully eradicate most of the neuroblastoma xenografts."	( Enhanced antitumor effect of lower-dose and longer-term CPT-11 treatment in combination with low-dose celecoxib against neuroblastoma xenografts. Fukushima, T; Kaneko, M; Kaneko, S, 2013)	0.39
"The efficacy of bevacizumab combined with infusional 5-fluorouracil/leucovorin (5-FU/LV) plus irinotecan (FOLFIRI) as the second-line treatment for metastatic colorectal cancer (mCRC) has not been fully clarified, although bevacizumab combined with infusional 5-FU/LV plus oxaliplatin (FOLFOX) in the second-line setting has demonstrated a survival benefit."	( Bevacizumab in combination with irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI) in patients with metastatic colorectal cancer who were previously treated with oxaliplatin-containing regimens: a multicenter observational cohort study (TCTG 2nd-BV stud Baba, E; Bando, H; Boku, N; Esaki, T; Fukunaga, M; Hyodo, I; Kato, S; Katsumata, K; Miyake, Y; Moriwaki, T; Ozeki, M; Satoh, T; Takashima, A; Yamashita, K; Yamazaki, K; Yoshida, S, 2012)	0.38
" Paclitaxel and campthothecin demonstrated the most prominent cytotoxic effect in combination with carbon ion radiotherapy."	( In vitro evaluation of photon and carbon ion radiotherapy in combination with chemotherapy in glioblastoma cells. Brons, S; Combs, SE; Debus, J; Haberer, T; Habermehl, D; Rieken, S; Weber, KJ; Winter, M; Zipp, L, 2012)	0.38
" We investigated the antitumor effect and mechanism of synergism when indisulam was administered in combination with CPT-11."	( Therapeutic potential and molecular mechanism of a novel sulfonamide anticancer drug, indisulam (E7070) in combination with CPT-11 for cancer treatment. Asada, M; Kusano, K; Owa, T; Ozawa, Y; Yokoi, A; Yoshimatsu, K, 2012)	0.38
"Cetuximab combined with irinotecan when administered biweekly is safe and effective for treatment of pretreated elderly patients with mCRC."	( Anti-EGFR (cetuximab) combined with irinotecan for treatment of elderly patients with metastatic colorectal cancer (mCRC). Abdel-Aziz, H; Abdelwahab, S; Azmy, A; Mahmoud, A; Salim, H, 2012)	0.38
" Firstly, viability, apoptosis and caspase assays were performed during incubation with either the inhibitors alone or combined with different cytotoxic agents."	( Selective PI3K inhibition by BKM120 and BEZ235 alone or in combination with chemotherapy in wild-type and mutated human gastrointestinal cancer cell lines. Bachmann, E; Galle, PR; Khillimberger, K; Linnig, M; Moehler, M; Mueller, A; Schimanski, CC, 2012)	0.38
" Furthermore, BEZ235 caused synergistic induction of apoptosis when combined with irinotecan in colon cancer cell lines."	( Selective PI3K inhibition by BKM120 and BEZ235 alone or in combination with chemotherapy in wild-type and mutated human gastrointestinal cancer cell lines. Bachmann, E; Galle, PR; Khillimberger, K; Linnig, M; Moehler, M; Mueller, A; Schimanski, CC, 2012)	0.38
"Leucovorin Sodium (LV/Na) has a high solubility, and is stable when given with continuous infusion of 5-FU."	( A phase II randomized study of combined infusional leucovorin sodium and 5- FU versus the leucovorin calcium followed by 5-FU both in combination with irinotecan or oxaliplatin in patients with metastatic colorectal cancer. Bleiberg, H; D'Haens, G; Deleu, I; Efira, A; Humblet, Y; Paesmans, M; Peeters, M; Rezaei Kalantari, H; Vandebroek, A; Vergauwe, P, 2012)	0.38
"Fifty seven patients with mCRC and no previous chemotherapy for metastatic disease were randomized to receive LV/Na or LV/Ca with irinotecan or oxaliplatine combined with infusional 5-FU."	( A phase II randomized study of combined infusional leucovorin sodium and 5- FU versus the leucovorin calcium followed by 5-FU both in combination with irinotecan or oxaliplatin in patients with metastatic colorectal cancer. Bleiberg, H; D'Haens, G; Deleu, I; Efira, A; Humblet, Y; Paesmans, M; Peeters, M; Rezaei Kalantari, H; Vandebroek, A; Vergauwe, P, 2012)	0.38
"The efficacy and tolerability of bevacizumab every 2 or 4 weeks using the same dosage in combination with biweekly FOLFIRI were retrospectively evaluated in metastatic colorectal cancer (mCRC) patients in the first-line and second-line therapy."	( Bevacizumab every 4 weeks is as effective as every 2 weeks in combination with biweekly FOLFIRI in metastatic colorectal cancer. Alkis, N; Benekli, M; Berk, V; Buyukberber, S; Ciltas, A; Coskun, U; Dane, F; Dikilitas, M; Dogu, GG; Durnali, AG; Kaplan, MA; Karaca, H; Ozkan, M; Sevinc, A; Yetisyigit, T; Yildiz, R, 2012)	0.38
" The patients had received biweekly FOLFIRI in combination with bevacizumab 5 mg/kg every 2 weeks or every 4 weeks schedule for various reasons in individual patients."	( Bevacizumab every 4 weeks is as effective as every 2 weeks in combination with biweekly FOLFIRI in metastatic colorectal cancer. Alkis, N; Benekli, M; Berk, V; Buyukberber, S; Ciltas, A; Coskun, U; Dane, F; Dikilitas, M; Dogu, GG; Durnali, AG; Kaplan, MA; Karaca, H; Ozkan, M; Sevinc, A; Yetisyigit, T; Yildiz, R, 2012)	0.38
"Bevacizumab 5 mg/kg every 2 weeks or every 4 weeks in combination with biweekly FOLFIRI had similar efficacy and tolerability in mCRC."	( Bevacizumab every 4 weeks is as effective as every 2 weeks in combination with biweekly FOLFIRI in metastatic colorectal cancer. Alkis, N; Benekli, M; Berk, V; Buyukberber, S; Ciltas, A; Coskun, U; Dane, F; Dikilitas, M; Dogu, GG; Durnali, AG; Kaplan, MA; Karaca, H; Ozkan, M; Sevinc, A; Yetisyigit, T; Yildiz, R, 2012)	0.38
" Recently, fluorouracil/leucovorin combined with irinotecan and oxaliplatin (FOLFIRINOX) demonstrated their superiority in first-line therapy."	( Influcence of localization of primary tumor on effectiveness of 5-fluorouracil/leucovorin combined with irinotecan and oxaliplatin (FOLFIRINOX) in patients with metastatic pancreatic adenocarcinoma: a retrospective study. Chauffert, B; Gentil, J; Ghiringhelli, F; Lorgis, V, 2012)	0.38
" The present study evaluated the synergetic toxicity of DATR in combination with traditional chemotherapeutics, including irinotecan, polyene paclitaxel and oxaliplatin in rats."	( Synergetic toxicity of DATR, a recombinant soluble human TRAIL mutant, in combination with traditional chemotherapeutics in rats. Chu, Z; Huang, M; Lu, G; Mao, Y; Yuan, B; Zhang, X; Zou, Y, 2012)	0.38
" Thus, a meta-analysis was conducted to assess the efficacy and safety of bevacizumab compared to bevacizumab combined with irinotecan for the treatment of recurrent GBM."	( A meta-analysis of bevacizumab alone and in combination with irinotecan in the treatment of patients with recurrent glioblastoma multiforme. Huang, S; Wang, Z; Zhang, G, 2012)	0.38
" In the USA, the approval of cetuximab has been recently expanded to include the first-line treatment of patients with KRAS mutation-negative (wild-type), EGFR-expressing, metastatic colorectal cancer (mCRC) when used in combination with FOLFIRI (irinotecan, fluorouracil, leucovorin [folinic acid])."	( Cetuximab: a guide to its use in combination with FOLFIRI in the first-line treatment of metastatic colorectal cancer in the USA. Lyseng-Williamson, KA, 2012)	0.38
" Thus, we investigated the effect of JMR-132 in combination with S-phase-specific cytotoxic agents, 5-FU, irinotecan and cisplatin on the in vitro and in vivo growth of HT-29, HCT-116 and HCT-15 human colon cancer cell lines."	( GHRH antagonist when combined with cytotoxic agents induces S-phase arrest and additive growth inhibition of human colon cancer. Block, NL; Buchholz, S; Datz, C; Hohla, F; Krishan, A; Rick, FG; Schally, AV; Seitz, S; Stadlmayr, A; Szalontay, L, 2012)	0.38
"This prospective observational study assessed the efficacy of bevacizumab in combination with chemotherapy as preoperative treatment to downsize tumours for radical resection in patients with unresectable metastatic colorectal cancer (mCRC)."	( Preoperative treatment with bevacizumab in combination with chemotherapy in patients with unresectable metastatic colorectal carcinoma. Albiol, M; Alsina, M; Codina-Barreras, A; Figueras, J; Guardeño, R; Hernandez-Yagüe, X; Lopez-Ben, S; Queralt, B; Soriano, J, 2013)	0.39
" Preoperative treatment consisted of bevacizumab (5 mg/kg) combined with oxaliplatin- or irinotecan-based chemotherapy, which was followed by surgery in patients showing clinical benefit."	( Preoperative treatment with bevacizumab in combination with chemotherapy in patients with unresectable metastatic colorectal carcinoma. Albiol, M; Alsina, M; Codina-Barreras, A; Figueras, J; Guardeño, R; Hernandez-Yagüe, X; Lopez-Ben, S; Queralt, B; Soriano, J, 2013)	0.39
"We retrospectively assessed the safety and efficacy of BEV alone or combined with irinotecan in 39 patients with recurrent grade II/III gliomas."	( Bevacizumab alone or in combination with irinotecan in recurrent WHO grade II and grade III gliomas. Happold, C; Hundsberger, T; Seystahl, K; Weller, M; Wick, A; Wick, W; Wiestler, B, 2013)	0.39
"Both BEV monotherapy and its combination with irinotecan were well tolerated."	( Bevacizumab alone or in combination with irinotecan in recurrent WHO grade II and grade III gliomas. Happold, C; Hundsberger, T; Seystahl, K; Weller, M; Wick, A; Wick, W; Wiestler, B, 2013)	0.39
"The aims of this study were to establish the maximum tolerated dose (MTD) of oxaliplatin in combination with fixed doses of gemcitabine, irinotecan, and 5-fluorouracil/leucovorin (G-FLIE) in solid tumors, including advanced pancreatic cancer, and to evaluate the toxicity of the regimen."	( Phase I study of oxaliplatin in combination with gemcitabine, irinotecan, and 5-fluorouracil/leucovorin (G-FLIE) in patients with metastatic solid tumors including adenocarcinoma of the pancreas. Chalasani, SB; Chung, MS; Grossbard, ML; Kozuch, PS; Malamud, S; Mirzoyev, T; Olszewski, AJ, 2013)	0.39
" The aim of the study was to determine the maximum tolerated dose (MTD) and recommended dose (RD) of BV combined with irinotecan plus S-1, and to observe the safety and efficacy of this regimen as second-line chemotherapy in patients with advanced colorectal cancer."	( Phase I study of bevacizumab combined with irinotecan and S-1 as second-line chemotherapy in patients with advanced colorectal cancer. Akashi, K; Arita, S; Baba, E; Esaki, T; Kishimoto, J; Kumagai, H; Kusaba, H; Mitsugi, K; Uchino, K, 2013)	0.39
" UCN-01, a non-selective Chk1 inhibitor, combined with irinotecan demonstrated activity in advanced TNBC in our Phase I study."	( A phase II study of UCN-01 in combination with irinotecan in patients with metastatic triple negative breast cancer. Bernard, PS; Brenin, CM; Cai, SR; Craig Lockhart, A; Creekmore, AN; Dancey, J; Doyle, LA; Ebbert, M; Ellis, MJ; Fracasso, PM; Guo, Z; Ma, CX; Mwandoro, T; Naughton, MJ; Petroni, GR; Picus, J; Piwnica-Worms, H; Pluard, TJ; Reed, J; Ryan, CE; Watson, M; Yarde, ER, 2013)	0.39
" Patients were treated with cetuximab combined with either CAPIRI or CAPOX."	( Early tumor shrinkage in patients with metastatic colorectal cancer receiving first-line treatment with cetuximab combined with either CAPIRI or CAPOX: an analysis of the German AIO KRK 0104 trial. Giessen, C; Haas, M; Heinemann, V; Laubender, RP; Mansmann, U; Modest, DP; Schulz, C; Stintzing, S, 2013)	0.39
" The multitargeted kinase inhibitor, regorafenib, was combined with chemotherapy as first- or second-line treatment of mCRC to assess safety and pharmacokinetics (primary objectives) and tumor response (secondary objective)."	( Regorafenib in combination with FOLFOX or FOLFIRI as first- or second-line treatment of colorectal cancer: results of a multicenter, phase Ib study. Boix, O; Ehrenberg, R; Fischer, R; Folprecht, G; Hacker, UT; Hamann, S; Köhne, CH; Kornacker, M; Krauss, J; Kuhlmann, J; Lettieri, J; Mross, KB; Schultheis, B; Strumberg, D, 2013)	0.39
"Regorafenib had acceptable tolerability in combination with chemotherapy, with increased exposure of irinotecan and SN-38 but no significant effect on 5-fluorouracil or oxaliplatin pharmacokinetics."	( Regorafenib in combination with FOLFOX or FOLFIRI as first- or second-line treatment of colorectal cancer: results of a multicenter, phase Ib study. Boix, O; Ehrenberg, R; Fischer, R; Folprecht, G; Hacker, UT; Hamann, S; Köhne, CH; Kornacker, M; Krauss, J; Kuhlmann, J; Lettieri, J; Mross, KB; Schultheis, B; Strumberg, D, 2013)	0.39
"The aim of this study was to investigate the efficacy and safety of belotecan in combination with cisplatin in patients with previously non-treated extensive stage small cell lung cancer."	( Phase II study of camtobell inj. (belotecan) in combination with cisplatin in patients with previously untreated, extensive stage small cell lung cancer. Chang, J; Cho, BC; Jung, JY; Kim, D; Kim, EY; Kim, GM; Kim, HR; Kim, HS; Kim, JH; Kim, SH; Kim, SK; Kim, YS; Lee, JH; Lim, S; Lim, SM; Park, JS; Park, MS, 2013)	0.39
" We evaluated the efficacy and safety of conatumumab (an agonistic monoclonal antibody against human death receptor 5) and ganitumab (a monoclonal antibody against the type 1 insulin-like growth factor receptor) combined with standard FOLFIRI chemotherapy as a second-line treatment in patients with mutant KRAS mCRC."	( A randomized, placebo-controlled phase 2 study of ganitumab or conatumumab in combination with FOLFIRI for second-line treatment of mutant KRAS metastatic colorectal cancer. Choo, SP; Chuah, BYS; Cohn, AL; Cottrell, S; Dubey, S; Galimi, F; Hei, YJ; Kopp, MV; Loberg, R; Maurel, J; McCaffery, I; Mitchell, EP; Nowara, E; Pan, Y; Sakaeva, DD; Sastre, J; Suzuki, S; Tabernero, J, 2013)	0.39
" Patients with histologically proven gastrointestinal neuroendocrine carcinoma who were treated with irinotecan combined with 5-fluorouracil and leucovorin in a first-line setting were eligible for analysis."	( First-line irinotecan combined with 5-fluorouracil and leucovorin for high-grade metastatic gastrointestinal neuroendocrine carcinoma. Du, Z; Li, Q; Wang, Y; Wen, F; Zhou, Y, )	0.13
"The results demonstrated that irinotecan combined with 5-fluorouracil and leucovorin is an active regimen with acceptable toxicity for patients with metastatic high-grade gastointestinal neuroendocrine carcinoma that merits further investigation in prospective trials."	( First-line irinotecan combined with 5-fluorouracil and leucovorin for high-grade metastatic gastrointestinal neuroendocrine carcinoma. Du, Z; Li, Q; Wang, Y; Wen, F; Zhou, Y, )	0.13
"Poly(ADP-ribose) polymerase inhibitors (PARPi) are currently evaluated in clinical trials in combination with topoisomerase I (Top1) inhibitors against a variety of cancers, including colon carcinoma."	( Influence of MLH1 on colon cancer sensitivity to poly(ADP-ribose) polymerase inhibitor combined with irinotecan. Campolo, F; Dolci, S; Dorio, AS; Graziani, G; Lacal, PM; Leonetti, C; Muzi, A; Porru, M; Praz, F; Tentori, L; Vernole, P, 2013)	0.39
" CPT-11 treatment alone or combined with blocking monoclonal antibodies (mAb) against co-stimulatory molecules (LFA-1 and CD154) was evaluated in the prevention of heart transplant rejection in alloantigen-primed mice."	( Irinotecan combined with co-stimulatory molecule blockade prolongs survival of cardiac allografts in alloantigen-primed mice. Chen, J; Chen, Z; Cheng, P; He, Z; Liu, Z; Qi, Z; Yang, R; Zhang, S, 2013)	0.39
" This pilot study demonstrates the utility of using yeast for screening large matrices of drug combinations, and it provides a means to prioritize drug combination tests in human cells."	( A high-throughput yeast assay identifies synergistic drug combinations. Brown, GW; Giaever, G; Lee, AY; Nislow, C; Torres, NP, 2013)	0.39
"The safety, tolerability, and pharmacokinetic (PK) interactions of MK-0646 in combination with cetuximab and irinotecan were investigated in Japanese patients with advanced colorectal cancer."	( Phase 1 pharmacokinetic study of MK-0646 (dalotuzumab), an anti-insulin-like growth factor-1 receptor monoclonal antibody, in combination with cetuximab and irinotecan in Japanese patients with advanced colorectal cancer. Doi, T; Feng, HP; Fuse, N; Muro, K; Noguchi, K; Ohtsu, A; Shimamoto, T; Takahari, D; Ura, T; Yoshino, T, 2013)	0.39
" Therefore we evaluate the efficacy and safety of irinotecan in combination with nedaplatin/cisplatin against refractory or relapsed small cell lung cancer."	( [A retrospective study of the efficacy and toxicity of irinotecan in combination with nedaplatin versus irinotecan in combination with cisplatin as salvage treatment in refractory or relapsed small cell lung cancer]. Hao, X; Hu, X; Li, J; Shi, Y; Wang, H; Wang, Y; Xu, J; Yu, S; Zhang, X, 2013)	0.39
"The antiangiogenic agent aflibercept (ziv-aflibercept in the United States) in combination with 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) significantly improved survival in a phase III study of patients with metastatic colorectal cancer (mCRC) previously treated with an oxaliplatin-based regimen."	( Aflibercept versus placebo in combination with fluorouracil, leucovorin and irinotecan in the treatment of previously treated metastatic colorectal cancer: prespecified subgroup analyses from the VELOUR trial. Allegra, CJ; Chevalier, S; Ferry, DR; Lakomý, R; McKendrick, JJ; Moiseyenko, VM; Prausová, J; Ruff, P; Soussan-Lazard, K; Tabernero, J; Van Cutsem, E; van Hazel, GA, 2014)	0.4
"The benefits of aflibercept in combination with FOLFIRI in patients with mCRC previously treated with oxaliplatin were maintained across the specified patient subgroups, including in patients with or without prior bevacizumab treatment."	( Aflibercept versus placebo in combination with fluorouracil, leucovorin and irinotecan in the treatment of previously treated metastatic colorectal cancer: prespecified subgroup analyses from the VELOUR trial. Allegra, CJ; Chevalier, S; Ferry, DR; Lakomý, R; McKendrick, JJ; Moiseyenko, VM; Prausová, J; Ruff, P; Soussan-Lazard, K; Tabernero, J; Van Cutsem, E; van Hazel, GA, 2014)	0.4
" In addition three other human tumour cell lines (A549: lung, LN-229: glioblastoma, PANC-1: pancreas) were tested for the combination with camptothecin."	( Comparison of the effects of photon versus carbon ion irradiation when combined with chemotherapy in vitro. Brons, S; Combs, SE; Debus, J; Haberer, T; Schlaich, F; Weber, KJ, 2013)	0.59
" In combination with chemotherapy additive toxicity was the prevailing effect."	( Comparison of the effects of photon versus carbon ion irradiation when combined with chemotherapy in vitro. Brons, S; Combs, SE; Debus, J; Haberer, T; Schlaich, F; Weber, KJ, 2013)	0.39
"This phase I study evaluated the safety of SU5416, a potent and selective inhibitor of the vascular endothelial growth factor (VEGF) receptor tyrosine kinase Flk-1, in combination with weekly cisplatin and irinotecan in patients with advanced solid tumors."	( A phase I dose escalation and pharmacodynamic study of SU5416 (semaxanib) combined with weekly cisplatin and irinotecan in patients with advanced solid tumors. Bekaii-Saab, T; Clinton, SK; Grever, MR; Kraut, EH; Martin, LK; Monk, P; Serna, D, 2013)	0.39
"SU5416 at 65 mg/m² twice weekly combined with cisplatin and irinotecan weekly for 4 of 6 weeks is well tolerated but without evidence of clinical activity."	( A phase I dose escalation and pharmacodynamic study of SU5416 (semaxanib) combined with weekly cisplatin and irinotecan in patients with advanced solid tumors. Bekaii-Saab, T; Clinton, SK; Grever, MR; Kraut, EH; Martin, LK; Monk, P; Serna, D, 2013)	0.39
"To determine the maximum tolerated dose of irinotecan administered every 2 weeks, in combination with a fixed and continuous administration of temozolomide, in patients with glioblastoma at first relapse."	( A phase I study of irinotecan in combination with metronomic temozolomide in patients with recurrent glioblastoma. Balañá, C; Gallego, O; García, JL; Iglesias, L; Pérez, P; Reynés, G, 2014)	0.4
" Here, we evaluate the safety and pharmacokinetics of efatutazone combined with FOLFIRI (5-fluorouracil, levo-leucovorin, and irinotecan) as second-line chemotherapy in Japanese patients with mCRC."	( Phase 1 study of efatutazone, a novel oral peroxisome proliferator-activated receptor gamma agonist, in combination with FOLFIRI as second-line therapy in patients with metastatic colorectal cancer. Hyodo, I; Komatsu, Y; Machida, N; Ohtsu, A; Onuma, H; Sasaki, T; Yachi, Y; Yamazaki, K; Yoshino, T; Yuki, S, 2014)	0.4
"50 mg (the recommended dose [RD] of efatutazone monotherapy) twice daily in combination with FOLFIRI in a 3-9 patient cohort."	( Phase 1 study of efatutazone, a novel oral peroxisome proliferator-activated receptor gamma agonist, in combination with FOLFIRI as second-line therapy in patients with metastatic colorectal cancer. Hyodo, I; Komatsu, Y; Machida, N; Ohtsu, A; Onuma, H; Sasaki, T; Yachi, Y; Yamazaki, K; Yoshino, T; Yuki, S, 2014)	0.4
"Efatutazone combined with FOLFIRI demonstrates an acceptable safety profile and evidence of disease stabilization in Japanese patients with mCRC."	( Phase 1 study of efatutazone, a novel oral peroxisome proliferator-activated receptor gamma agonist, in combination with FOLFIRI as second-line therapy in patients with metastatic colorectal cancer. Hyodo, I; Komatsu, Y; Machida, N; Ohtsu, A; Onuma, H; Sasaki, T; Yachi, Y; Yamazaki, K; Yoshino, T; Yuki, S, 2014)	0.4
", in a week-on/week-off schedule, combined with FOLFIRI or FOLFOX."	( Intermittent dosing of axitinib combined with chemotherapy is supported by (18)FLT-PET in gastrointestinal tumours. Bendell, JC; Burris, HA; Hoh, CK; Infante, JR; Kim, S; Reid, TR; Rosbrook, B; Tarazi, J, 2014)	0.4
"Axitinib administered in a week-on/week-off schedule combined with FOLFIRI or FOLFOX is supported by (18)FLT-PET data and was well tolerated in patients with gastrointestinal tumours."	( Intermittent dosing of axitinib combined with chemotherapy is supported by (18)FLT-PET in gastrointestinal tumours. Bendell, JC; Burris, HA; Hoh, CK; Infante, JR; Kim, S; Reid, TR; Rosbrook, B; Tarazi, J, 2014)	0.4
"To investigate the efficacy of treatment with siRNA targeting Bcl-2 in combination with HCPT against H₂₂ hepatoma transplanted in mice."	( [Efficacy of treatment with siRNA targeting Bcl-2 in combination with HCPT against transplanted H₂₂ hepatoma in mice]. Hu, HH; Song, HX, 2013)	0.39
" Then, the Bcl-2 siRNA was transfected into H₂₂ hepatoma transplanted in mice in combination with HCPT for treatment."	( [Efficacy of treatment with siRNA targeting Bcl-2 in combination with HCPT against transplanted H₂₂ hepatoma in mice]. Hu, HH; Song, HX, 2013)	0.39
"31)mm³ in the group of siRNA in combination with HCPT, which was significant smaller than that of the groups of HCPT [(880."	( [Efficacy of treatment with siRNA targeting Bcl-2 in combination with HCPT against transplanted H₂₂ hepatoma in mice]. Hu, HH; Song, HX, 2013)	0.39
"Bcl-2 siRNA in combination with HCPT has good synergetic antitumor efficacy in H₂₂ hepatoma-bearing mice."	( [Efficacy of treatment with siRNA targeting Bcl-2 in combination with HCPT against transplanted H₂₂ hepatoma in mice]. Hu, HH; Song, HX, 2013)	0.39
"We conclude that bortezomib is not effective for the treatment of advanced adenocarcinoma of the GEJ or stomach, whether used alone or in combination with irinotecan, in an unselected patient population."	( Phase II trial of bortezomib alone or in combination with irinotecan in patients with adenocarcinoma of the gastroesophageal junction or stomach. Besanceney-Webler, C; Chen, EX; Cheng, J; Christos, P; Dilts, KT; Holloway, S; Keresztes, R; Lane, ME; Lin, J; Matulich, D; Ocean, AJ; Papetti, M; Schnoll-Sussman, F; Shah, MA; Sparano, JA; Ward, M; Wright, JJ; Xiang, J; Yantiss, RK, 2014)	0.4
"To evaluate the efficacy and safety of trastuzumab combined with chemotherapy in the treatment for HER-2-positive chemo-refractory advanced gastric or gastro-esophageal junction adenocarcinoma."	( [Trastuzumab combined with chemotherapy in patients with HER2-positive chemo-refractory advanced gastric or gastro-esophageal junction adenocarcinoma]. Cao, Y; Gong, J; Li, J; Li, Y; Lu, M; Lu, Z; Shen, L; Wang, X; Wu, Y; Zhang, X; Zhou, J, 2014)	0.4
"A dose escalation study of biweekly irinotecan (CPT-11) combined with capecitabine was performed to determine the maximum tolerated dose (MTD) and recommended dose (RD) for metastatic breast cancer (MBC) previously treated with anthracyclines and taxanes."	( A phase I study of capecitabine combined with CPT-11 in metastatic breast cancer pretreated with anthracyclines and taxanes. Inaba, T; Ishida, K; Kashiwaba, M; Kawagishi, R; Komatsu, H; Matsui, Y; Sugai, T; Uesugi, N; Wakabayashi, G, 2014)	0.4
" The aim of the present study was to explore whether CFZ alone or in combination with CPT-11 is effective in CRC treatment."	( Enhanced anti-colorectal cancer effects of carfilzomib combined with CPT-11 via downregulation of nuclear factor-κB in vitro and in vivo. Chen, Q; Chen, S; Huang, C; Li, J; Liao, J; Liu, F; Su, G; Tang, W; Ye, Y, 2014)	0.4
"To estimate the incremental cost per life-year gained (LYG) of aflibercept in combination with FOLFIRI as second-line treatment in metastatic colorectal cancer (mCRC) patients previously treated with oxaliplatin."	( [Cost-effectiveness analysis of aflibercept in combination with FOLFIRI in the treatment of patients with metastatic colorectal cancer]. Abad, A; Echave, M; Frías, C; Giménez, E; Joulain, F; Lamas, MJ; Naoshy, S; Oyagüez, I; Pericay, C; Rubio, M, 2014)	0.4
" In the cost-effectiveness analysis Euros 38,931/LYG was obtained with aflibercept in combination with FOLFIRI versus FOLFIRI."	( [Cost-effectiveness analysis of aflibercept in combination with FOLFIRI in the treatment of patients with metastatic colorectal cancer]. Abad, A; Echave, M; Frías, C; Giménez, E; Joulain, F; Lamas, MJ; Naoshy, S; Oyagüez, I; Pericay, C; Rubio, M, 2014)	0.4
"Aflibercept in combination with FOLFIRI increased overall survival versus FOLFIRI, so it is an effective strategy in the treatment of patients with mCRC."	( [Cost-effectiveness analysis of aflibercept in combination with FOLFIRI in the treatment of patients with metastatic colorectal cancer]. Abad, A; Echave, M; Frías, C; Giménez, E; Joulain, F; Lamas, MJ; Naoshy, S; Oyagüez, I; Pericay, C; Rubio, M, 2014)	0.4
" This study aimed to evaluate the maximum tolerated regimen (MTR), safety, and pharmacokinetics of pazopanib in combination with irinotecan and cetuximab in adult patients with relapsed or refractory metastatic colorectal cancer (mCRC)."	( A phase I open-label study of the safety, tolerability, and pharmacokinetics of pazopanib in combination with irinotecan and cetuximab for relapsed or refractory metastatic colorectal cancer. Bennouna, J; Botbyl, J; de Labareyre, C; Delord, JP; Deslandres, M; Ruiz-Soto, R; Senellart, H; Suttle, AB; Wixon, C, 2015)	0.42
"This was a Phase I, 3 + 3 design, open-label, dose-escalation study (NCT0050943; VEG108925) conducted in sequential cohorts to determine the MTR of pazopanib and irinotecan administered with cetuximab."	( A phase I open-label study of the safety, tolerability, and pharmacokinetics of pazopanib in combination with irinotecan and cetuximab for relapsed or refractory metastatic colorectal cancer. Bennouna, J; Botbyl, J; de Labareyre, C; Delord, JP; Deslandres, M; Ruiz-Soto, R; Senellart, H; Suttle, AB; Wixon, C, 2015)	0.42
"The MTR was determined to be 400 mg pazopanib per day orally in combination with 150 mg/m(2) irinotecan biweekly and 250 mg/m(2) cetuximab weekly by infusion."	( A phase I open-label study of the safety, tolerability, and pharmacokinetics of pazopanib in combination with irinotecan and cetuximab for relapsed or refractory metastatic colorectal cancer. Bennouna, J; Botbyl, J; de Labareyre, C; Delord, JP; Deslandres, M; Ruiz-Soto, R; Senellart, H; Suttle, AB; Wixon, C, 2015)	0.42
" This trial was designed to assess the tolerability of different doses of abituzumab in combination with cetuximab and irinotecan (phase I) and explore the efficacy and tolerability of the combination versus that of cetuximab and irinotecan in patients with metastatic CRC (mCRC) (phase II part)."	( Abituzumab combined with cetuximab plus irinotecan versus cetuximab plus irinotecan alone for patients with KRAS wild-type metastatic colorectal cancer: the randomised phase I/II POSEIDON trial. Bokemeyer, C; Bruns, R; Csőszi, T; Élez, E; Höhler, T; Kocáková, I; Martens, UM; Melichar, B; Orlova, R; Quaratino, S; Rivera, F; Smakal, M; Straub, J; Tabernero, J; Tjulandin, S; Topuzov, E; Van Cutsem, E, 2015)	0.42
" The trial comprised an initial safety run-in using abituzumab doses up to 1000 mg combined with a standard of care (SoC: cetuximab plus irinotecan) and a phase II part in which patients were randomised 1 : 1 : 1 to receive abituzumab 500 mg (arm A) or 1000 mg (arm B) every 2 weeks combined with SoC, or SoC alone (arm C)."	( Abituzumab combined with cetuximab plus irinotecan versus cetuximab plus irinotecan alone for patients with KRAS wild-type metastatic colorectal cancer: the randomised phase I/II POSEIDON trial. Bokemeyer, C; Bruns, R; Csőszi, T; Élez, E; Höhler, T; Kocáková, I; Martens, UM; Melichar, B; Orlova, R; Quaratino, S; Rivera, F; Smakal, M; Straub, J; Tabernero, J; Tjulandin, S; Topuzov, E; Van Cutsem, E, 2015)	0.42
"Phase I showed that abituzumab doses up to 1000 mg were well tolerated in combination with SoC."	( Abituzumab combined with cetuximab plus irinotecan versus cetuximab plus irinotecan alone for patients with KRAS wild-type metastatic colorectal cancer: the randomised phase I/II POSEIDON trial. Bokemeyer, C; Bruns, R; Csőszi, T; Élez, E; Höhler, T; Kocáková, I; Martens, UM; Melichar, B; Orlova, R; Quaratino, S; Rivera, F; Smakal, M; Straub, J; Tabernero, J; Tjulandin, S; Topuzov, E; Van Cutsem, E, 2015)	0.42
" The tolerability of abituzumab combined with cetuximab and irinotecan was acceptable."	( Abituzumab combined with cetuximab plus irinotecan versus cetuximab plus irinotecan alone for patients with KRAS wild-type metastatic colorectal cancer: the randomised phase I/II POSEIDON trial. Bokemeyer, C; Bruns, R; Csőszi, T; Élez, E; Höhler, T; Kocáková, I; Martens, UM; Melichar, B; Orlova, R; Quaratino, S; Rivera, F; Smakal, M; Straub, J; Tabernero, J; Tjulandin, S; Topuzov, E; Van Cutsem, E, 2015)	0.42
"The National Institute for Health and Care Excellence (NICE) invited the manufacturer of aflibercept (Sanofi) to submit clinical and cost-effectiveness evidence for aflibercept in combination with irinotecan and fluorouracil-based therapy [irinotecan/5-fluorouracil/folinic acid (FOLFIRI)] for the treatment of metastatic colorectal cancer which has progressed following prior oxaliplatin-based chemotherapy, as part of the Institute's Single Technology Appraisal process."	( The Clinical and Cost Effectiveness of Aflibercept in Combination with Irinotecan and Fluorouracil-Based Therapy (FOLFIRI) for the Treatment of Metastatic Colorectal Cancer Which has Progressed Following Prior Oxaliplatin-Based Chemotherapy: a Critique of Duarte, A; Duffy, S; Rodriguez-Lopez, R; Simmonds, M; Spackman, E; Wade, R; Woolacott, N, 2015)	0.42
"These findings suggest the potential roles of HM781-36B as the treatment for EGFR-overexpressing colon cancer, singly or in combination with chemotherapeutic agents."	( Antitumor Activity of HM781-36B, alone or in Combination with Chemotherapeutic Agents, in Colorectal Cancer Cells. Kang, MH; Kim, JH; Kim, JW; Lee, HS; Lee, JS; Lee, KW; Moon, SU; Sung, JH, 2016)	0.43
"The purpose of this study is to compare the efficacy of a single administration of dexamethasone (DEX) on day 1 against DEX administration on days 1-3 in combination with palonosetron (PALO), a second-generation 5-HT3 receptor antagonist, for chemotherapy-induced nausea and vomiting (CINV) in non-anthracycline and cyclophosphamide (AC) moderately-emetogenic chemotherapy (MEC)."	( Open-label, randomized, comparative, phase III study on effects of reducing steroid use in combination with Palonosetron. Eto, K; Fukushima, H; Furuhata, T; Isobe, H; Iwanaga, I; Kawamoto, Y; Komatsu, Y; Kudo, M; Masuko, H; Minami, S; Miyagishima, T; Nakajima, J; Nakamura, M; Oba, K; Ohsaki, Y; Okita, K; Sasaki, K; Shibuya, H; Takahashi, Y; Tateyama, M; Yokoyama, R; Yuki, S, 2015)	0.42
" We assessed the efficacy and safety of ramucirumab versus placebo in combination with second-line FOLFIRI (leucovorin, fluorouracil, and irinotecan) for metastatic colorectal cancer in patients with disease progression during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine."	( Ramucirumab versus placebo in combination with second-line FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): a randomised, double-blin Bodoky, G; Chang, SC; Ciuleanu, TE; Clingan, PR; Cohn, AL; Garcia-Alfonso, P; Garcia-Carbonero, R; Grothey, A; Kim, TW; Lonardi, S; Nasroulah, F; Obermannova, R; Portnoy, DC; Prausová, J; Simms, L; Tabernero, J; Van Cutsem, E; Yamazaki, K; Yoshino, T, 2015)	0.42
"To explore the clinical efficacy and toxic and side effects of recombinant human endostatin (rh- endostatin/endostar) combined with chemotherapy in the treatment of advanced gastric cancer."	( Clinical observation on recombinant human endostatin combined with chemotherapy for advanced gastrointestinal cancer. Gao, SR; Li, LM; Wang, AR; Wang, GM; Xia, HP; Xu, HY, 2015)	0.42
"Preliminary observations show that endostar (once every other day) combined with chemotherapy is effective in the treatment of advanced gastrointestinal cancer, with low toxic effects, good tolerance, deserving further study."	( Clinical observation on recombinant human endostatin combined with chemotherapy for advanced gastrointestinal cancer. Gao, SR; Li, LM; Wang, AR; Wang, GM; Xia, HP; Xu, HY, 2015)	0.42
" This novel siRNA based drug was studied, in combination with chemotherapy, as targeted therapy for Locally Advanced Pancreatic Cancer (LAPC)."	( RNAi therapy targeting KRAS in combination with chemotherapy for locally advanced pancreatic cancer patients. Dancour, A; David, EB; Domb, A; Eliakim, R; Gabai, RM; Galun, E; Golan, T; Goldes, Y; Goldin, E; Harari, G; Hen, N; Hubert, A; Khvalevsky, EZ; Kopleman, Y; Lahav, M; Raskin, S; Segal, A; Shemi, A, 2015)	0.42
"We conducted a phase I dose escalation study to evaluate the feasibility, maximum tolerated dose (MTD), and recommended dose (RD) of weekly irinotecan combined with fixed-dose carboplatin for patients with untreated small-cell lung cancer (SCLC)."	( Weekly irinotecan combined with carboplatin for patients with small-cell lung cancer: A phase I study. Inoue, A; Ishimoto, O; Maemondo, M; Nukiwa, T; Sugawara, S, 2015)	0.42
" The remission rate, control rate and time to disease progression were compared among patients receiving cetuximab combined with different chemotherapy regimens in different periods."	( [Clinical efficacy observation of cetuximab combined with chemotherapy in the treatment of metastatic colorectal carcinoma]. Bai, L; Han, C; Jiao, S; Li, J; Su, D; Wang, Y; Zhang, T, 2015)	0.42
"Cetuximab in combination with oxaliplatin-based chemotherapy is recommended as the first-line application in the treatment of metastatic colorectal carcinoma patients, because it is helpful to improve the rate of disease control."	( [Clinical efficacy observation of cetuximab combined with chemotherapy in the treatment of metastatic colorectal carcinoma]. Bai, L; Han, C; Jiao, S; Li, J; Su, D; Wang, Y; Zhang, T, 2015)	0.42
"5mg/kg every alternate week (arm B), or placebo (arm C) in combination with cetuximab and irinotecan."	( A Randomized Phase II/III Study of Dalotuzumab in Combination With Cetuximab and Irinotecan in Chemorefractory, KRAS Wild-Type, Metastatic Colorectal Cancer. Ayers, M; Clarke, SJ; Cunningham, D; Ferry, D; Frödin, JE; Guren, TK; Hawkes, E; Kim, SY; Kim, TW; Kim, TY; Loboda, A; Mauro, DJ; Nebozhyn, M; Park, YS; Peckitt, C; Roh, JK; Schmoll, HJ; Sclafani, F; Tabernero, J; Watkins, DJ, 2015)	0.42
"The oral Bcl-2 inhibitor navitoclax demonstrated activity in solid and hematologic malignancies as monotherapy and in combination with other cytotoxic agents in preclinical and early clinical studies."	( Safety, efficacy, and pharmacokinetics of navitoclax (ABT-263) in combination with irinotecan: results of an open-label, phase 1 study. Arzt, J; Busman, TA; Holen, KD; Lian, G; LoRusso, P; Rosen, LS; Rudersdorf, NS; Tolcher, AW; Vanderwal, CA; Waring, JF; Yang, J, 2015)	0.42
"In this multicenter, open-label, phase 1 dose escalation study, adults with advanced solid tumors received navitoclax (starting dose 150 mg/day) in combination with 1 of 2 irinotecan schedules during a 21-day cycle: a once-every-3-week regimen (Q3W 180, 250, or 350 mg/m(2)) or a once-weekly regimen (QW 75 or 100 mg/m(2))."	( Safety, efficacy, and pharmacokinetics of navitoclax (ABT-263) in combination with irinotecan: results of an open-label, phase 1 study. Arzt, J; Busman, TA; Holen, KD; Lian, G; LoRusso, P; Rosen, LS; Rudersdorf, NS; Tolcher, AW; Vanderwal, CA; Waring, JF; Yang, J, 2015)	0.42
" In the QW group, the MTD and RPTD for navitoclax were 150 mg when combined with irinotecan 75 mg/m(2)."	( Safety, efficacy, and pharmacokinetics of navitoclax (ABT-263) in combination with irinotecan: results of an open-label, phase 1 study. Arzt, J; Busman, TA; Holen, KD; Lian, G; LoRusso, P; Rosen, LS; Rudersdorf, NS; Tolcher, AW; Vanderwal, CA; Waring, JF; Yang, J, 2015)	0.42
"The RPTD of navitoclax in combination with irinotecan 75 mg/m(2) QW during a 21-day cycle was 150 mg in these heavily pretreated patients."	( Safety, efficacy, and pharmacokinetics of navitoclax (ABT-263) in combination with irinotecan: results of an open-label, phase 1 study. Arzt, J; Busman, TA; Holen, KD; Lian, G; LoRusso, P; Rosen, LS; Rudersdorf, NS; Tolcher, AW; Vanderwal, CA; Waring, JF; Yang, J, 2015)	0.42
" In the present study, to address this concern, we proposed a novel strategy of preparing self-assembled nanoparticles from amphiphilic drug-drug conjugate for synergistic combination chemotherapy."	( Synergistic Combination Chemotherapy of Camptothecin and Floxuridine through Self-Assembly of Amphiphilic Drug-Drug Conjugate. Hu, M; Huang, P; Su, Y; Wang, Y; Yan, D; Zhou, L; Zhu, X, 2015)	0.68
" Herein, we critically discuss the current data on the efficacy and safety profile of bevacizumab in combination with fluoropyrimidine-based chemotherapy for first-line and maintenance treatment of metastatic CRC and briefly comment on existing controversies and future perspectives."	( Bevacizumab in combination with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy for first-line and maintenance treatment of metastatic colorectal cancer. Grapsa, D; Saif, MW; Syrigos, K, 2015)	0.42
" This phase I trial sought to determine the maximum tolerable dose (MTD) of bevacizumab and sorafenib combined with standard cytotoxic therapy for advanced gastrointestinal (GI) cancers."	( Phase I trial of FOLFIRI in combination with sorafenib and bevacizumab in patients with advanced gastrointestinal malignancies. Borad, MJ; Erlichman, C; Grothey, A; Hubbard, JM; Johnson, E; Kim, G; Lensing, J; Puttabasavaiah, S; Qin, R; Wright, J, 2016)	0.43
"A standard 3 + 3 trial design utilized 3 escalating sorafenib dose levels: (1) 200 mg daily, days 3-7, 10-14; (2) 200 mg twice daily, days 3-6, 10-13; and (3) 200 mg twice daily, days 3-7, 10-14 combined with standard dose FOLFIRI (5-fluouracil, leucovorin, and irinotecan) and bevacizumab (5 mg/kg), repeated every 14 days."	( Phase I trial of FOLFIRI in combination with sorafenib and bevacizumab in patients with advanced gastrointestinal malignancies. Borad, MJ; Erlichman, C; Grothey, A; Hubbard, JM; Johnson, E; Kim, G; Lensing, J; Puttabasavaiah, S; Qin, R; Wright, J, 2016)	0.43
" The MTD was determined to be dose level 2: sorafenib 200 mg twice daily, days 3-6, 10-13 combined with FOLFIRI and bevacizumab at standard doses."	( Phase I trial of FOLFIRI in combination with sorafenib and bevacizumab in patients with advanced gastrointestinal malignancies. Borad, MJ; Erlichman, C; Grothey, A; Hubbard, JM; Johnson, E; Kim, G; Lensing, J; Puttabasavaiah, S; Qin, R; Wright, J, 2016)	0.43
"The MTD of this regimen is sorafenib 200 mg twice daily, days 3-6, 10-13 combined with standard doses of FOLFIRI and bevacizumab."	( Phase I trial of FOLFIRI in combination with sorafenib and bevacizumab in patients with advanced gastrointestinal malignancies. Borad, MJ; Erlichman, C; Grothey, A; Hubbard, JM; Johnson, E; Kim, G; Lensing, J; Puttabasavaiah, S; Qin, R; Wright, J, 2016)	0.43
" We investigated if arsenic sulfide (As4S4) in combination with other distinct agents could enhance its cytotoxic activity."	( Arsenic sulfide combined with JQ1, chemotherapy agents, or celecoxib inhibit gastric and colon cancer cell growth. Chen, S; Pan, M; Tong, Y; Zhang, L; Zhang, X, 2015)	0.42
"We used gastric and colon cancer cell lines to study the synergistic effect of As4S4 in combination with BRD4 inhibitor JQ1, or with chemotherapy drug cisplatin and irinotecan or with COX2 inhibitor celecoxib."	( Arsenic sulfide combined with JQ1, chemotherapy agents, or celecoxib inhibit gastric and colon cancer cell growth. Chen, S; Pan, M; Tong, Y; Zhang, L; Zhang, X, 2015)	0.42
"We found that when As4S4 was combined with JQ1, cisplatin, irinotecan or celecoxib, its cytotoxic activity was dramatically enhanced in both gastric and colon cancer cell lines."	( Arsenic sulfide combined with JQ1, chemotherapy agents, or celecoxib inhibit gastric and colon cancer cell growth. Chen, S; Pan, M; Tong, Y; Zhang, L; Zhang, X, 2015)	0.42
"As4S4 in combination with JQ1, cisplatin, irinotecan or celecoxib showed enhanced cytotoxic effect on gastric and colon cancer cells, indicating the potential application of these novel drug combinations as part of treatment strategy that warrants further investigation."	( Arsenic sulfide combined with JQ1, chemotherapy agents, or celecoxib inhibit gastric and colon cancer cell growth. Chen, S; Pan, M; Tong, Y; Zhang, L; Zhang, X, 2015)	0.42
" A nonrandomized phase 1 dose-escalation study of ABT-751 in combination with CAPIRI (capecitabine and irinotecan) and bevacizumab was conducted to define the maximum tolerated dose, dose-limiting toxicity (DLT), and pharmacokinetics in patients with advanced colorectal cancer."	( Phase 1 Study of ABT-751 in Combination With CAPIRI (Capecitabine and Irinotecan) and Bevacizumab in Patients With Advanced Colorectal Cancer. Dasari, A; Donehower, RC; He, P; Hidalgo, M; Jimeno, A; Jin, R; Laheru, D; Messersmith, WA; Purcell, WT; Rudek, MA; Taylor, GE; Walker, R, 2016)	0.43
"To investigate the anticancer effect and its mechanism of SN-38 combined with sorafenib on hepatocellular cancer cell lines HepG-2 and BEL-7402."	( [Anticancer effect of SN-38 combined with sorafenib on hepatocellular carcinoma in vitro and its mechanism]. Jian, C; Pei-hua, L; Xiao-chun, Y; Xu, L; Yuan-run, Z, 2015)	0.42
"SRB colorimetry showed the synergistic anticancer activities of SN-38 combined with sorafenib, with a combination index of <0."	( [Anticancer effect of SN-38 combined with sorafenib on hepatocellular carcinoma in vitro and its mechanism]. Jian, C; Pei-hua, L; Xiao-chun, Y; Xu, L; Yuan-run, Z, 2015)	0.42
"High-dose FOLFIRI combined with cetuximab yielded high response rates and enabled complete resection of class II hepatic metastases in most patients."	( High Resectability Rate of Initially Unresectable Colorectal Liver Metastases After UGT1A1-Adapted High-Dose Irinotecan Combined with LV5FU2 and Cetuximab: A Multicenter Phase II Study (ERBIFORT). Buc, E; Chatelut, E; De la Fouchardière, C; Mendoza, C; Mineur, L; Pezet, D; Phelip, JM; Quesada, JL; Rivoire, M; Roblin, X, 2016)	0.43
" This phase I study determined the MTD, dose-limiting toxicities (DLT), pharmacokinetics (PK), and pharmacodynamics (PD) of veliparib, an orally bioavailable PARP1/2 inhibitor, in combination with irinotecan."	( Phase I Safety, Pharmacokinetic, and Pharmacodynamic Study of the Poly(ADP-ribose) Polymerase (PARP) Inhibitor Veliparib (ABT-888) in Combination with Irinotecan in Patients with Advanced Solid Tumors. Bell, T; Boerner, JL; Boerner, SA; Bowditch, A; Burger, A; Cai, D; Chen, AP; Cleary, JM; Ferry-Galow, K; Heilbrun, LK; Ji, J; Kinders, RJ; Li, J; LoRusso, PM; Marrero, AM; Parchment, RE; Pilat, MJ; Rubinstein, L; Sausville, EA; Shapiro, GI; Smith, D; Tolaney, SM; Wolanski, A; Zhang, J; Zhang, Y, 2016)	0.43
" The MTD was 100 mg/m(2) irinotecan (days 1 and 8) combined with veliparib 40 mg twice daily (days -1-14) on a 21-day cycle."	( Phase I Safety, Pharmacokinetic, and Pharmacodynamic Study of the Poly(ADP-ribose) Polymerase (PARP) Inhibitor Veliparib (ABT-888) in Combination with Irinotecan in Patients with Advanced Solid Tumors. Bell, T; Boerner, JL; Boerner, SA; Bowditch, A; Burger, A; Cai, D; Chen, AP; Cleary, JM; Ferry-Galow, K; Heilbrun, LK; Ji, J; Kinders, RJ; Li, J; LoRusso, PM; Marrero, AM; Parchment, RE; Pilat, MJ; Rubinstein, L; Sausville, EA; Shapiro, GI; Smith, D; Tolaney, SM; Wolanski, A; Zhang, J; Zhang, Y, 2016)	0.43
"Veliparib can be safely combined with irinotecan at doses that inhibit PARP catalytic activity."	( Phase I Safety, Pharmacokinetic, and Pharmacodynamic Study of the Poly(ADP-ribose) Polymerase (PARP) Inhibitor Veliparib (ABT-888) in Combination with Irinotecan in Patients with Advanced Solid Tumors. Bell, T; Boerner, JL; Boerner, SA; Bowditch, A; Burger, A; Cai, D; Chen, AP; Cleary, JM; Ferry-Galow, K; Heilbrun, LK; Ji, J; Kinders, RJ; Li, J; LoRusso, PM; Marrero, AM; Parchment, RE; Pilat, MJ; Rubinstein, L; Sausville, EA; Shapiro, GI; Smith, D; Tolaney, SM; Wolanski, A; Zhang, J; Zhang, Y, 2016)	0.43
"To compare the efficacy and safety of two chemotherapeutic regimens, irinotecan monotherapy or irinotecan in combination with fluoropyrimidines, for patients with advanced CRC when administered in the first or second-line settings."	( Irinotecan chemotherapy combined with fluoropyrimidines versus irinotecan alone for overall survival and progression-free survival in patients with advanced and/or metastatic colorectal cancer. Repana, D; Van Hemelrijck, M; Wardhana, A; Watkins, J; Wulaningsih, W; Yoshuantari, N, 2016)	0.43
"Randomized controlled trials (RCTs) investigating the efficacy and safety of IRI chemotherapy combined with fluoropyrimidine compared with IRI alone for the treatment of patients with advanced CRC, regardless of treatment line settings."	( Irinotecan chemotherapy combined with fluoropyrimidines versus irinotecan alone for overall survival and progression-free survival in patients with advanced and/or metastatic colorectal cancer. Repana, D; Van Hemelrijck, M; Wardhana, A; Watkins, J; Wulaningsih, W; Yoshuantari, N, 2016)	0.43
" Pharmacokinetic testing did not show evidence of drug-drug interaction between irinotecan and alisertib."	( Phase I Study of the Aurora A Kinase Inhibitor Alisertib in Combination With Irinotecan and Temozolomide for Patients With Relapsed or Refractory Neuroblastoma: A NANT (New Approaches to Neuroblastoma Therapy) Trial. Bagatell, R; Courtier, J; Czarnecki, S; DuBois, SG; Fox, E; Goodarzian, F; Groshen, S; Hawkins, R; Kudgus, RA; Lai, H; Malvar, J; Marachelian, A; Maris, JM; Matthay, KK; Mosse, YP; Reid, JM; Shimada, H; Tsao-Wei, D; Wagner, L, 2016)	0.43
"Cetuximab in combination with an irinotecan-containing regimen is a standard treatment in patients with KRAS wild-type (KRAS WT), metastatic colorectal cancer (mCRC)."	( A randomized, placebo-controlled, phase 1/2 study of tivantinib (ARQ 197) in combination with irinotecan and cetuximab in patients with metastatic colorectal cancer with wild-type KRAS who have received first-line systemic therapy. Barni, S; Bendell, JC; Bessudo, A; Bolotin, E; Eng, C; Gladkov, O; Hart, LL; Hsu, C; Kopp, MV; Kotiv, B; Langdon, R; Müller, L; Schwartz, B; Severtsev, A; Vladimirov, V; von Roemeling, R, 2016)	0.43
" We aimed to establish the safety, tolerability, and recommended phase 2 oral dose of the CCR2 inhibitor PF-04136309 in combination with FOLFIRINOX chemotherapy (oxaliplatin and irinotecan plus leucovorin and fluorouracil)."	( Targeting tumour-associated macrophages with CCR2 inhibition in combination with FOLFIRINOX in patients with borderline resectable and locally advanced pancreatic cancer: a single-centre, open-label, dose-finding, non-randomised, phase 1b trial. Belt, BA; Cusworth, BM; DeNardo, DG; Fields, RC; Fowler, KJ; Goedegebuure, SP; Hawkins, WG; Lim, KH; Linehan, DC; Lockhart, AC; Nieman, RK; Nywening, TM; Panni, RZ; Sanford, DE; Strasberg, SM; Suresh, R; Tan, BR; Toriola, AT; Wang-Gillam, A; Worley, LA; Yano, M, 2016)	0.43
" Patients were allocated to receive either FOLFIRINOX alone (oxaliplatin 85 mg/m(2), irinotecan 180 mg/m(2), leucovorin 400 mg/m(2), and bolus fluorouracil 400 mg/m(2), followed by 2400 mg/m(2) 46-h continuous infusion), administered every 2 weeks for a total of six treatment cycles, or in combination with oral PF-04136309, administered at a starting dose of 500 mg twice daily in a standard 3 + 3 dose de-escalation design."	( Targeting tumour-associated macrophages with CCR2 inhibition in combination with FOLFIRINOX in patients with borderline resectable and locally advanced pancreatic cancer: a single-centre, open-label, dose-finding, non-randomised, phase 1b trial. Belt, BA; Cusworth, BM; DeNardo, DG; Fields, RC; Fowler, KJ; Goedegebuure, SP; Hawkins, WG; Lim, KH; Linehan, DC; Lockhart, AC; Nieman, RK; Nywening, TM; Panni, RZ; Sanford, DE; Strasberg, SM; Suresh, R; Tan, BR; Toriola, AT; Wang-Gillam, A; Worley, LA; Yano, M, 2016)	0.43
"CCR2-targeted therapy with PF-04136309 in combination with FOLFIRINOX is safe and tolerable."	( Targeting tumour-associated macrophages with CCR2 inhibition in combination with FOLFIRINOX in patients with borderline resectable and locally advanced pancreatic cancer: a single-centre, open-label, dose-finding, non-randomised, phase 1b trial. Belt, BA; Cusworth, BM; DeNardo, DG; Fields, RC; Fowler, KJ; Goedegebuure, SP; Hawkins, WG; Lim, KH; Linehan, DC; Lockhart, AC; Nieman, RK; Nywening, TM; Panni, RZ; Sanford, DE; Strasberg, SM; Suresh, R; Tan, BR; Toriola, AT; Wang-Gillam, A; Worley, LA; Yano, M, 2016)	0.43
" We evaluated the ability of ceramide, a bioactive sphingolipid, to predict tumour sensitivity in patients treated by hypofractionated stereotactic body radiation therapy (SBRT) combined with irinotecan chemotherapy."	( Plasma ceramide, a real-time predictive marker of pulmonary and hepatic metastases response to stereotactic body radiation therapy combined with irinotecan. Campion, L; Carrie, C; Dubois, N; Ferchaud-Roucher, V; Gaugler, MH; Krempf, M; Mahé, M; Mirabel, X; Paris, F; Rio, E; Ripoche, N, 2016)	0.43
"Total plasma ceramide is a promising biomarker of tumour response to SBRT combined with irinotecan that should enable to segregate patients with high risk of tumour escape."	( Plasma ceramide, a real-time predictive marker of pulmonary and hepatic metastases response to stereotactic body radiation therapy combined with irinotecan. Campion, L; Carrie, C; Dubois, N; Ferchaud-Roucher, V; Gaugler, MH; Krempf, M; Mahé, M; Mirabel, X; Paris, F; Rio, E; Ripoche, N, 2016)	0.43
" We found that cetuximab, in combination with chemotherapy, fostered ICD in CRC cells, which we measured via the endoplasmic reticulum (ER) stress response and an increase in phagocytosis by dendritic cells."	( The EGFR-specific antibody cetuximab combined with chemotherapy triggers immunogenic cell death. Bardelli, A; Bonaldi, T; Cancelliere, C; Conte, A; Cuomo, A; Di Fiore, PP; Magni, E; Penna, G; Pozzi, C; Ravenda, PS; Rescigno, M; Sigismund, S; Silvola, A; Spadoni, I; Zampino, MG, 2016)	0.43
" An additive antiproliferative effect was observed in combination with irinotecan."	( Modulation of tumor eIF4E by antisense inhibition: A phase I/II translational clinical trial of ISIS 183750-an antisense oligonucleotide against eIF4E-in combination with irinotecan in solid tumors and irinotecan-refractory colorectal cancer. Abdullah, S; Abi-Jaoudeh, N; Anderson, V; Duffy, AG; Figg, WD; Fioravanti, S; Greten, TF; Lee, S; Levy, E; MacLeod, AR; Makarova-Rusher, OV; Peer, CJ; Raffeld, M; Rahma, OE; Revenko, AS; Steinberg, SM; Tomita, Y; Trepel, JB; Ulahannan, SV; Walker, M; Wood, BJ, 2016)	0.43
" It is unknown whether these antibodies, such as cetuximab, are more efficacious in refractory metastatic colorectal cancer as monotherapy, or in combination with irinotecan."	( ICECREAM: randomised phase II study of cetuximab alone or in combination with irinotecan in patients with metastatic colorectal cancer with either KRAS, NRAS, BRAF and PI3KCA wild type, or G13D mutated tumours. Chantrill, L; Ciardiello, F; Day, F; Desai, J; Elez, E; Gebski, V; Haydon, A; Jefford, M; Joubert, W; Karapetis, C; Khasraw, M; Nott, L; Pavlakis, N; Price, T; Segelov, E; Shapiro, J; Tebbutt, N; Tejpar, S; Thavaneswaran, S; Underhill, C; van Hazel, G; Waring, P; Wasan, H; Wilson, K, 2016)	0.43
" We investigated the pharmacologic characteristics of OTX015 as a single agent and combined with targeted therapy or conventional chemotherapies in glioblastoma cell lines."	( OTX015 (MK-8628), a novel BET inhibitor, displays in vitro and in vivo antitumor effects alone and in combination with conventional therapies in glioblastoma models. Astorgues-Xerri, L; Bekradda, M; Berenguer-Daizé, C; Cayol, M; Cvitkovic, E; Lokiec, F; MacKenzie, S; Noel, K; Odore, E; Ouafik, L; Rezai, K; Riveiro, ME, 2016)	0.43
" This study aimed to compare the overall survival (OS) of HAI-FUDR in combination with modern systemic CT versus modern systemic CT alone in patients with IU-CRCLM."	( Hepatic Arterial Infusion in Combination with Modern Systemic Chemotherapy is Associated with Improved Survival Compared with Modern Systemic Chemotherapy Alone in Patients with Isolated Unresectable Colorectal Liver Metastases: A Case-Control Study. Bahary, N; Bartlett, DL; Choudry, MH; Clifford, AK; Dhir, M; Hogg, ME; Holtzman, MP; Jones, HL; Perkins, S; Pingpank, JF; Shuai, Y; Steve, J; Zeh, HJ; Zureikat, AH, 2017)	0.46
"In this case-control study of patients with IU-CRCLM, HAI in combination with CT was associated with improved OS when compared with modern systemic CT alone."	( Hepatic Arterial Infusion in Combination with Modern Systemic Chemotherapy is Associated with Improved Survival Compared with Modern Systemic Chemotherapy Alone in Patients with Isolated Unresectable Colorectal Liver Metastases: A Case-Control Study. Bahary, N; Bartlett, DL; Choudry, MH; Clifford, AK; Dhir, M; Hogg, ME; Holtzman, MP; Jones, HL; Perkins, S; Pingpank, JF; Shuai, Y; Steve, J; Zeh, HJ; Zureikat, AH, 2017)	0.46
"CRLX101 combined with bevacizumab is safe in mRCC."	( Efficacy of the nanoparticle-drug conjugate CRLX101 in combination with bevacizumab in metastatic renal cell carcinoma: results of an investigator-initiated phase I-IIa clinical trial. Ciconte, J; Cohen, RB; Eliasof, S; Garmey, EG; Gunnarsson, O; Haas, NB; Heitjan, D; Hennessy, M; Hoffman-Censits, J; Jayaraman, L; Keefe, SM; Mamtani, R; Nixon, A; Piscitelli, A; Senderowicz, A; Smith, A; Tellez, AB; Turnbull, B; Vaughn, D; Waliki, M, 2016)	0.43
"The objective of this phase II study was to evaluate the potential of pharmacokinetic (PK) drug-drug interactions between ramucirumab and irinotecan or its metabolite, SN-38, when administered with folinic acid and 5-fluorouracil (FOLFIRI)."	( Lack of pharmacokinetic drug-drug interaction between ramucirumab and irinotecan in patients with advanced solid tumors. Asakiewicz, C; Braiteh, F; Chaudhary, A; Denlinger, CS; Gao, L; Lee, JJ; Lin, Y; LoRusso, P; Nasroulah, F; Shepard, DR; Wang, D, 2016)	0.43
"There was no PK drug-drug interaction between ramucirumab and irinotecan or its metabolite, SN-38."	( Lack of pharmacokinetic drug-drug interaction between ramucirumab and irinotecan in patients with advanced solid tumors. Asakiewicz, C; Braiteh, F; Chaudhary, A; Denlinger, CS; Gao, L; Lee, JJ; Lin, Y; LoRusso, P; Nasroulah, F; Shepard, DR; Wang, D, 2016)	0.43
" This randomized phase II study evaluated the antitumor activity and safety of icrucumab and ramucirumab each in combination with mFOLFOX-6 in patients with metastatic colorectal cancer after disease progression on first-line therapy with a fluoropyrimidine and irinotecan."	( Randomized phase II study of modified FOLFOX-6 in combination with ramucirumab or icrucumab as second-line therapy in patients with metastatic colorectal cancer after disease progression on first-line irinotecan-based therapy. Alcindor, T; Asmis, T; Bendell, J; Berry, S; Binder, P; Burkes, R; Chan, E; Chan, T; Gao, L; Gill, S; Jeyakumar, A; Kambhampati, SR; Kauh, J; Kudrik, F; Moore, M; Nasroulah, F; Ramdas, N; Rao, S; Rothenstein, J; Spratlin, J; Strevel, E; Tang, PA; Tang, S; Yang, L; Zbuk, K, 2016)	0.43
"Eligible patients were randomly assigned to receive mFOLFOX-6 alone (mFOLFOX-6) or in combination with ramucirumab 8 mg/kg IV (RAM+mFOLFOX-6) or icrucumab 15 mg/kg IV (ICR+mFOLFOX-6) every 2 weeks."	( Randomized phase II study of modified FOLFOX-6 in combination with ramucirumab or icrucumab as second-line therapy in patients with metastatic colorectal cancer after disease progression on first-line irinotecan-based therapy. Alcindor, T; Asmis, T; Bendell, J; Berry, S; Binder, P; Burkes, R; Chan, E; Chan, T; Gao, L; Gill, S; Jeyakumar, A; Kambhampati, SR; Kauh, J; Kudrik, F; Moore, M; Nasroulah, F; Ramdas, N; Rao, S; Rothenstein, J; Spratlin, J; Strevel, E; Tang, PA; Tang, S; Yang, L; Zbuk, K, 2016)	0.43
" These changes can increase the risk of drug-drug interactions (DDIs) in patients on multiple medications."	( Role of Toll-like receptor 4 in drug-drug interaction between paclitaxel and irinotecan in vitro. Basu, S; Ghose, R; Mallick, P; Moorthy, B, 2017)	0.46
"The CONCERT study (observational cohort study of patients with metastatic colorectal cancer initiating chemotherapy in combination with bevacizumab) aimed to describe patient characteristics, bevacizumab use, its efficacy in terms of progression-free survival (PFS) and overall survival (OS), and its safety in patients with metastatic colorectal cancer (mCRC) treated in daily medical practice."	( Observational Cohort Study of Patients With Metastatic Colorectal Cancer Initiating Chemotherapy in Combination With Bevacizumab (CONCERT). André, T; Asselain, B; Bennouna, J; Ducreux, M; Phelip, JM, 2017)	0.46
" Patients with mCRC initiating bevacizumab combined with chemotherapy were included and followed up for ≤ 36 months."	( Observational Cohort Study of Patients With Metastatic Colorectal Cancer Initiating Chemotherapy in Combination With Bevacizumab (CONCERT). André, T; Asselain, B; Bennouna, J; Ducreux, M; Phelip, JM, 2017)	0.46
" Bevacizumab was mainly started at 5 mg/kg every 2 weeks (95%) and mostly combined with FOLFIRI (leucovorin, 5-fluorouracil, irinotecan; 68."	( Observational Cohort Study of Patients With Metastatic Colorectal Cancer Initiating Chemotherapy in Combination With Bevacizumab (CONCERT). André, T; Asselain, B; Bennouna, J; Ducreux, M; Phelip, JM, 2017)	0.46
"In this phase 1 dose-escalation trial in patients with unresectable PDAC, we determined the maximum tolerated dose (MTD) of olaparib (tablet formulation) in combination with irinotecan 70 mg/m2 on days 1 and 8 and cisplatin 25 mg/m2 on days 1 and 8 of a 28-day cycle (olaparib plus IC)."	( Olaparib in combination with irinotecan, cisplatin, and mitomycin C in patients with advanced pancreatic cancer. Azad, NS; De Jesus-Acosta, A; Donehower, RC; Fine, RL; Goggins, M; Jaffee, EM; Johnson, BA; Laheru, DA; Le, DT; Myzak, MC; Oberstein, PE; Yarchoan, M; Zheng, L, 2017)	0.46
"Olaparib had substantial toxicity when combined with IC or ICM in patients with PDAC, and this treatment combination did not have an acceptable risk/benefit profile for further study."	( Olaparib in combination with irinotecan, cisplatin, and mitomycin C in patients with advanced pancreatic cancer. Azad, NS; De Jesus-Acosta, A; Donehower, RC; Fine, RL; Goggins, M; Jaffee, EM; Johnson, BA; Laheru, DA; Le, DT; Myzak, MC; Oberstein, PE; Yarchoan, M; Zheng, L, 2017)	0.46
"Cetuximab vs bevacizumab combined with either mFOLFOX6 or FOLFIRI chemotherapy regimen chosen by the treating physician and patient."	( Effect of First-Line Chemotherapy Combined With Cetuximab or Bevacizumab on Overall Survival in Patients With KRAS Wild-Type Advanced or Metastatic Colorectal Cancer: A Randomized Clinical Trial. Atkins, JN; Benson, AB; Berry, S; Bertagnolli, MM; Blanke, C; El-Khoueiry, AB; Fruth, B; Goldberg, RM; Greene, C; Hochster, HS; Innocenti, F; Lenz, HJ; Mayer, RJ; Meyerhardt, JA; Mulkerin, DL; Niedzwiecki, D; O'Neil, BH; O'Reilly, EM; Polite, BN; Schilsky, RL; Schrag, D; Venook, AP; Watson, P, 2017)	0.46
" The purpose of this study was to investigate the therapeutic effect of quercetin combined with irinotecan/SN-38 in the AGS human gastric cancer cell line in vitro and in vivo."	( Effects of quercetin combined with anticancer drugs on metastasis-associated factors of gastric cancer cells: in vitro and in vivo studies. Hou, YC; Lei, CS; Lin, MT; Pai, MH; Yeh, SL, 2018)	0.48
"Surgical resection combined with adjuvant chemotherapy is considered as the gold-standard treatment for advanced colorectal cancer patients."	( Effect of dendritic cell-cytokine-induced killer cells in patients with advanced colorectal cancer combined with first-line treatment. Chen, L; Huang, L; Lin, X; Xie, Y; Zheng, Q, 2017)	0.46
" Among these patients, 71 patients received first-line treatment only (non-DC-CIK group), while the other 71 patients who had similar demographic and clinical characteristics received a DC-CIK cell infusion combined with first-line treatment (DC-CIK group)."	( Effect of dendritic cell-cytokine-induced killer cells in patients with advanced colorectal cancer combined with first-line treatment. Chen, L; Huang, L; Lin, X; Xie, Y; Zheng, Q, 2017)	0.46
"Our results showed that patients with advanced colorectal cancer might benefit from DC-CIK immunotherapy combined with first-line therapy by significantly prolonging 5-year OS and PFS."	( Effect of dendritic cell-cytokine-induced killer cells in patients with advanced colorectal cancer combined with first-line treatment. Chen, L; Huang, L; Lin, X; Xie, Y; Zheng, Q, 2017)	0.46
"PRODIGE 41-BEVANEC is an academic randomized, phase II study designed to evaluate the efficacy of bevacizumab in combination with FOLFIRI after failure of CT1 in unknown primary NEC and GEP-NEC."	( Evaluating bevacizumab in combination with FOLFIRI after the failure of platinum-etoposide regimen in patients with advanced poorly differentiated neuroendocrine carcinoma: The PRODIGE 41-BEVANEC randomized phase II study. Assenat, E; Bouarioua, N; Cadiot, G; Coriat, R; Dahan, L; Dubreuil, O; Elhajbi, F; Ferru, A; Gangloff, A; Granger, V; Hautefeuille, V; Hentic, O; Kurtz, JE; Le Malicot, K; Lepage, C; Lepere, C; Lievre, A; Lombard-Bohas, C; Malka, D; Roquin, G; Scoazec, JY; Smith, D; Walter, T, 2018)	0.48
" We report 2 patients with para-aortic lymph node metastasis treated with 4 courses each of FOLFOX6 and FOLFIRI in combination with bevacizumab, which led to a complete response."	( [Five-Year Survival of Two Patients with Para-Aortic Lymph Node Metastasis Treated with Four FOLFOX6and Four FOLFIRI Courses in Combination with Bevacizumab]. Ohara, H; Yamamoto, H, 2018)	0.48
" Herein, two different anticancer drugs, camptothecin and chlorambucil, are successfully connected together by a disulfide linkage to get a novel drug-drug conjugated prodrug (G)."	( Construction of drug-drug conjugate supramolecular nanocarriers based on water-soluble pillar[6]arene for combination chemotherapy. Hu, XY; Liu, X; Shao, W; Sun, G; Wang, L; Zhu, JJ, 2018)	0.75
" Patients were randomly assigned (1:1) to either BEVZ92 or reference bevacizumab (5 mg/kg on day 1 of each cycle every 2 weeks) in combination with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) or fluorouracil, leucovorin, and irinotecan (FOLFIRI)."	( Bevacizumab biosimilar BEVZ92 versus reference bevacizumab in combination with FOLFOX or FOLFIRI as first-line treatment for metastatic colorectal cancer: a multicentre, open-label, randomised controlled trial. Abdalla, KC; Bondarenko, I; Del Campo García, A; Franke, F; Huerga, C; Melo Cruz, F; Mendonça Bariani, G; Millán, S; Ostwal, V; Paravisini, A; Peredpaya, S; Rahuman, SA; Ramesh, A; Roca, E; Romera, A; Shah, P; Shparyk, Y, 2018)	0.48
"Our results suggest that BEVZ92 and reference bevacizumab are pharmacokinetically bioequivalent and have no appreciable differences in efficacy, immunogenicity, and safety profiles as first-line treatment in combination with FOLFOX or FOLFIRI in patients with metastatic colorectal cancer."	( Bevacizumab biosimilar BEVZ92 versus reference bevacizumab in combination with FOLFOX or FOLFIRI as first-line treatment for metastatic colorectal cancer: a multicentre, open-label, randomised controlled trial. Abdalla, KC; Bondarenko, I; Del Campo García, A; Franke, F; Huerga, C; Melo Cruz, F; Mendonça Bariani, G; Millán, S; Ostwal, V; Paravisini, A; Peredpaya, S; Rahuman, SA; Ramesh, A; Roca, E; Romera, A; Shah, P; Shparyk, Y, 2018)	0.48
"In order to reduce the frequency and the severity of oxaliplatin-related sensory-neuropathy and preserve antitumor efficacy, we performed alternating 4 mFOLFOX6 and 4 FOLFIRI cycles, in combination with bevacizumab, in patients with metastatic colorectal cancer."	( [A Case of a Patient with Rectum Cancer with Multiple Metastases, Who Was Able to Undergo Conversion Therapy Using Alternating mFOLFOX6 and FOLFIRI Regimens in Combination with Alternating Cetuximab and Bevacizumab]. O'hara, H; Yamamoto, H, 2018)	0.48
"Polypharmacy of elderly oncology patients and fragmented medication management are well-known risk factors for drug-drug interactions (DDIs)."	( Nightmares and hallucinations with aprepitant and opium powder: a suspected drug-drug interaction. Azzouz, B; Bouché, O; Clarenne, J; Narjoux, G; Slimano, F; Zeller, PS, 2019)	0.51
" The studies observed patients with wild-type [Kirsten] rat sarcoma viral oncogene homolog ([K]RAS/RAS) metastatic colorectal cancer (mCRC), who had been treated with panitumumab in combination with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) in the first line or with panitumumab combined with fluorouracil, leucovorin, and irinotecan (FOLFIRI) in the second line following fluoropyrimidine-based chemotherapy."	( Prospective Observational Cohort Study to Describe the Use of Panitumumab in Combination with Chemotherapy in Real-World Clinical Practice for Patients with Wild-Type RAS mCRC. Bjorklof, K; Buchler, T; Csoszi, T; Demonty, G; Hebart, H; Kafatos, G; Kiehl, M; Koukakis, R; Kuhn, A; Tomasek, J, 2019)	0.51
" To test this hypothesis, we analyzed CEA and CA19-9 serum levels in patients with advanced colorectal cancer who received cetuximab in combination with chemotherapy."	( The Role of Serum CEA and CA19-9 in Efficacy Evaluations and Progression-Free Survival Predictions for Patients Treated with Cetuximab Combined with FOLFOX4 or FOLFIRI as a First-Line Treatment for Advanced Colorectal Cancer. Dai, G; Gou, M; Jia, J; Qian, N; Yang, F; Zhang, P, 2019)	0.51
"CEA and CA19-9 are useful indicators of therapeutic curative effect from cetuximab combined with first-line chemotherapy."	( The Role of Serum CEA and CA19-9 in Efficacy Evaluations and Progression-Free Survival Predictions for Patients Treated with Cetuximab Combined with FOLFOX4 or FOLFIRI as a First-Line Treatment for Advanced Colorectal Cancer. Dai, G; Gou, M; Jia, J; Qian, N; Yang, F; Zhang, P, 2019)	0.51
"Polytherapy (or drug combination cancer therapy (DCCT)), targeting multiple mechanisms associated with tumor proliferation, can efficiently maximize therapeutic efficacy, decrease drug dosage, and reduce drug resistance."	( Molecular Engineering-Based Aptamer-Drug Conjugates with Accurate Tunability of Drug Ratios for Drug Combination Targeted Cancer Therapy. Fang, X; Fu, T; He, N; Huang, Q; Peng, Y; Sun, W; Tan, W; Wang, P; Zhang, P; Zhao, Z; Zhou, F, 2019)	0.51
" In summary, an increased concentration of HCPT in tissues was observed when it was combined with JGGC through inhibition of efflux protein, with a synergistic enhancement of the anticancer effect observed through promotion of apoptosis and immunity due to a reversion of the Th1/Th2 shift."	( Tissue Distribution and Anti-Lung Cancer Effect of 10-Hydroxycamptothecin Combined with Platycodonis Radix and Glycyrrhizae Radix ET Rhizoma. Chen, H; Du, W; Li, G; Li, M; Liang, X; Yang, W; Zhang, C; Zhang, W, 2019)	0.76
"Dual stimuli-responsive camptothecin polymeric prodrugs (CPT Prodrugs) with grafted structures were designed via chemoenzymatic methods and combined with doxorubicin (DOX) for synergistic drug delivery to improve anticancer efficiency."	( GSH/pH dual-responsive biodegradable camptothecin polymeric prodrugs combined with doxorubicin for synergistic anticancer efficiency. Gu, B; Hu, ZE; Li, J; Liu, YH; Wang, N; Wu, WX; Xing, X; Yang, XL; Yu, XQ, 2019)	1.09
"gov, NCT01506167) that recruited patients with metastatic colorectal cancer scheduled to receive bevacizumab in combination with first-line chemotherapy as part of routine clinical practice."	( ACORN: Observational Study of Bevacizumab in Combination With First-Line Chemotherapy for Treatment of Metastatic Colorectal Cancer in the UK. Baijal, S; Chau, I; Cunningham, D; Ellis, R; Harrison, M; Khakoo, S; Ograbek, A; Pedley, I; Raouf, S; Ross, P; Steward, W; Tahir, S, 2019)	0.51
" In the NAPOLI-1 trial, liposomal irinotecan in combination with fluorouracil (nal-iri/5FU) was shown to improve overall survival when compared to fluorouracil alone for metastatic pancreatic cancer."	( Comparison of conventional versus liposomal irinotecan in combination with fluorouracil for advanced pancreatic cancer: a single-institution experience. Arango, MJ; Noonan, AM; Porter, K; Reardon, J; Tossey, JC; VanDeusen, JB, 2019)	0.51
"To investigate the effect of 2-deoxy-d-glucose (2-DG) combined with hydroxycamptothecin (HCPT) on anti-tumor activity of breast cancer cells and its mechanism."	( [Synergistic Effect of 2-deoxy-D-glucose Combined with Hydroxycamptothecin on Apoptosis of Breast Cancer Cells]. Ge, XM; Li, JH; Liu, H; Liu, YM; Sun, XJ; Zhang, P; Zhen, YN, 2019)	0.98
"5, 5, 10, 20 mmol/L), HCPT(0, 5, 10, 20, 40 μmol/L) and 2-DG (5 mmol/L) combined with HCPT."	( [Synergistic Effect of 2-deoxy-D-glucose Combined with Hydroxycamptothecin on Apoptosis of Breast Cancer Cells]. Ge, XM; Li, JH; Liu, H; Liu, YM; Sun, XJ; Zhang, P; Zhen, YN, 2019)	0.75
" Against this backdrop, the efficacy of nanoliposomal irinotecan(nal-IRI)in combination with fluorouracil and folinic acid(FF)for progressive metastatic pancreatic cancer after previous gemcitabine therapy was confirmed in Europe in 2015 ahead of Japan."	( [Nanoliposomal Irinotecan in Combination with Fluorouracil and Folinic Acid, As a New Option for Second-Line Treatment in Metastatic Pancreatic Cancer]. Ueno, M, 2020)	0.56
" The data sources were the VELOUR (Aflibercept Versus Placebo in Combination With Irinotecan and 5-FU in the Treatment of Patients With Metastatic Colorectal Cancer After Failure of an Oxaliplatin Based Regimen) and RAISE (Ramucirumab Versus Placebo in Combination With Second-Line FOLFIRI in Patients With Metastatic Colorectal Carcinoma That Progressed During or After First-Line Therapy With Bevacizumab, Oxaliplatin, and a Fluoropyrimidine) trials, which compared FOLFIRI alone with AFL or RAM in second-line treatment for mCRC."	( Comparative Cost-effectiveness of Aflibercept and Ramucirumab in Combination with Irinotecan and Fluorouracil-based Therapy for the Second-line Treatment of Metastatic Colorectal Cancer in Japan. Kashiwa, M; Matsushita, R, 2020)	0.56
"AtezoTRIBE is a prospective, open label, phase II, comparative trial in which initially unresectable and previously untreated mCRC patients, irrespective of microsatellite status, are randomized in a 1:2 ratio to receive up to 8 cycles of FOLFOXIRI/bevacizumab alone or in combination with atezolizumab, followed by maintenance with bevacizumab plus 5-fluoruracil/leucovorin with or without atezolizumab according to treatment arm until disease progression."	( AtezoTRIBE: a randomised phase II study of FOLFOXIRI plus bevacizumab alone or in combination with atezolizumab as initial therapy for patients with unresectable metastatic colorectal cancer. Antoniotti, C; Aprile, G; Bergamo, F; Boccaccino, A; Boni, L; Borelli, B; Brunella, DS; Corallo, S; Cremolini, C; Falcone, A; Grassi, E; Lonardi, S; Marmorino, F; Morano, F; Moretto, R; Pietrantonio, F; Racca, P; Rossini, D; Salvatore, L; Tamberi, S; Tamburini, E; Tortora, G, 2020)	0.56
" with mCRC RAS/BRAF mutated, in first line will receive nivolumab in combination with FOLFOXIRI/bevacizumab every 2 weeks for 8 cycles followed by maintenance with bevacizumab plus nivolumab every 2 weeks."	( Phase II study on first-line treatment of NIVolumab in combination with folfoxiri/bevacizumab in patients with Advanced COloRectal cancer RAS or BRAF mutated - NIVACOR trial (GOIRC-03-2018). Antonuzzo, L; Bergamo, F; Berselli, A; Bordonaro, R; Damato, A; Iachetta, F; Maiello, E; Nasti, G; Normanno, N; Pinto, C; Romagnani, A; Tonini, G; Zaniboni, A, 2020)	0.56
" Although the survival benefits when combined with chemotherapy have been determined, there are no studies comparing the two agents with chemotherapy in the second-line treatment."	( The effectiveness of cetuximab and panitumumab when combined with FOLFIRI in second-line treatment of KRAS wild type metastatic colorectal cancers. Single centre experience. Almuradova, E; Çakar, B; Doğanavşargil, B; Gürsoy, P; Harman, M; Karabulut, B; Karateke, M; Sezak, M, 2021)	0.62
" In this phase II study, we prospectively analyzed the efficacy and safety of raltitrexed combined with S-1 (RS regimen) in the treatment of mCRC after the failure of conventional chemotherapy."	( A prospective phase II study of raltitrexed combined with S-1 as salvage treatment for patients with refractory metastatic colorectal cancer. Chen, Z; Guo, W; Huang, M; Li, W; Qiu, L; Wang, C; Wang, Y; Yang, Y; Zhang, W; Zhang, X; Zhang, Z; Zhao, X; Zhu, X, 2021)	0.62
"The use of sodium levofolinate (Na-Lev) is safe in combination with continuous infusion 5-fluorouracil in patients with gastrointestinal tumors treated with the FOLFIRI regimen."	( Prospective Observational Study Comparing Calcium and Sodium Levofolinate in Combination with 5-Fluorouracil in the FOLFIRI Regimen. Bartolini, G; Crudi, L; Donati, C; Foca, F; Frassineti, GL; Masini, C; Matteucci, L; Monti, M; Pagan, F; Passardi, A; Rapposelli, I; Ruscelli, S; Sbaffi, S; Sullo, F; Valgiusti, M, 2021)	0.62
"The objectives of this study were to compare the safety profiles of sodium levofolinate (Na-Lev) and calcium levofolinate (Ca-Lev) in combination with 5-fluorouracil (5-FU) in the FOLFIRI regimen and to measure the organizational impact of the introduction of Na-Lev on drug production and administration."	( Prospective Observational Study Comparing Calcium and Sodium Levofolinate in Combination with 5-Fluorouracil in the FOLFIRI Regimen. Bartolini, G; Crudi, L; Donati, C; Foca, F; Frassineti, GL; Masini, C; Matteucci, L; Monti, M; Pagan, F; Passardi, A; Rapposelli, I; Ruscelli, S; Sbaffi, S; Sullo, F; Valgiusti, M, 2021)	0.62
"CRLX101 meets the clinical need for an effective and tolerable topoisomerase I inhibitor and can be safely combined with bevacizumab."	( Sequential Phase II clinical trials evaluating CRLX101 as monotherapy and in combination with bevacizumab in recurrent ovarian cancer. Birrer, MJ; Campos, SM; Chadda, KR; D'Ascanio, AM; Horowitz, NS; Konstantinopoulos, PA; Krasner, CN; Lee, H; Matulonis, UA; Penson, RT; Young, CL, 2021)	0.62
"Napabucasin 240 mg BID in combination with FOLFIRI and bevacizumab was tolerated, with a manageable safety profile in Japanese patients with metastatic CRC."	( Phase I study of napabucasin in combination with FOLFIRI + bevacizumab in Japanese patients with metastatic colorectal cancer. Bando, H; Iino, S; Kadowaki, S; Kageyama, R; Kawazoe, A; Masuishi, T; Muro, K; Taniguchi, H; Yoshino, T, 2021)	0.62
" HNK in combination with HCPT produces a synergistic cell-killing effect on bladder cancer cells."	( Mechanism of apoptotic induction on T24 cells by honokiol and its synergistic anticancer effect in combination with hydroxycamptothecin. Hu, Q; Lou, GG; Luo, YT; Xie, LP; Yao, HP, 2021)	0.83
"Doublet or triplet chemotherapy regimens in combination with anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibodies (mAb), such as cetuximab or panitumumab, or the anti-vascular endothelial growth factor mAb bevacizumab, are the current recommended standard of care therapies for unresectable metastatic colorectal cancer (mCRC)."	( Triplet chemotherapy in combination with anti-EGFR agents for the treatment of metastatic colorectal cancer: Current evidence, advances, and future perspectives. Cremolini, C; Esser, R; Falcone, A; Folprecht, G; Martinelli, E; Mazard, T; Modest, DP; Tsuji, A, 2022)	0.72
"To evaluate the efficacy and safety of apatinib combined with FOLFIRI in the first-line treatment of advanced metastatic colorectal cancer (mCRC) and explore potential factors of efficacy."	( Efficacy of apatinib combined with FOLFIRI in the first-line treatment of patients with metastatic colorectal cancer. Liu, H; Rong, X; Wang, J; Wang, Y; Yu, H; Zhao, J, 2022)	0.72
" They provided informed consent and were treated with apatinib combined with FOLFIRI according to the scheduled regimen until disease progression or unacceptable toxicity occurred."	( Efficacy of apatinib combined with FOLFIRI in the first-line treatment of patients with metastatic colorectal cancer. Liu, H; Rong, X; Wang, J; Wang, Y; Yu, H; Zhao, J, 2022)	0.72
"Apatinib combined with FOLFIRI for the first-line treatment of advanced unresectable mCRC showed good efficacy and safety."	( Efficacy of apatinib combined with FOLFIRI in the first-line treatment of patients with metastatic colorectal cancer. Liu, H; Rong, X; Wang, J; Wang, Y; Yu, H; Zhao, J, 2022)	0.72
"To evaluate the safety and effectiveness of aflibercept in combination with fluorouracil, leucovorin, and irinotecan (FOLFIRI) in Korean patients with metastatic colorectal cancer (mCRC) who progressed with oxaliplatin-containing regimen."	( Safety and effectiveness of aflibercept in combination with FOLFIRI in Korean patients with metastatic colorectal cancer who received oxaliplatin-containing regimen. Ahn, MS; Bae, BN; Baik, SH; Beom, SH; Han, SW; Jeon, SY; Jo, HJ; Kang, MH; Kim, DH; Kim, HK; Kim, JG; Kim, JH; Kim, JS; Kim, JY; Lee, MA; Lee, S; Oh, J; Park, I; Park, YS; Shin, SH; Yoon, JA; Zang, DY, 2023)	0.91
"Aflibercept in combination with FOLFIRI was effective and showed an acceptable safety profile in Korean patients with mCRC in daily clinical practice."	( Safety and effectiveness of aflibercept in combination with FOLFIRI in Korean patients with metastatic colorectal cancer who received oxaliplatin-containing regimen. Ahn, MS; Bae, BN; Baik, SH; Beom, SH; Han, SW; Jeon, SY; Jo, HJ; Kang, MH; Kim, DH; Kim, HK; Kim, JG; Kim, JH; Kim, JS; Kim, JY; Lee, MA; Lee, S; Oh, J; Park, I; Park, YS; Shin, SH; Yoon, JA; Zang, DY, 2023)	0.91
" This study aimed to evaluate the safety and tolerability with long-term survival rates in patients with colorectal cancer with unresectable metastases after treatment with first-line bevacizumab/FOLFIRI (folinic acid, bolus/continuous fluorouracil, and irinotecan) in combination with a dietary supplement of G-NLC."	( Long-term Survival, Tolerability, and Safety of First-Line Bevacizumab and FOLFIRI in Combination With Ginsenoside-Modified Nanostructured Lipid Carrier Containing Curcumin in Patients With Unresectable Metastatic Colorectal Cancer. Baek, JH; Jeon, Y; Sym, SJ; Yoo, BK, )	0.13
" The enrolled patients had colorectal cancer with unresectable metastases and were administered bevacizumab and FOLFIRI in combination with daily oral G-NLC as first-line treatment."	( Long-term Survival, Tolerability, and Safety of First-Line Bevacizumab and FOLFIRI in Combination With Ginsenoside-Modified Nanostructured Lipid Carrier Containing Curcumin in Patients With Unresectable Metastatic Colorectal Cancer. Baek, JH; Jeon, Y; Sym, SJ; Yoo, BK, )	0.13
"This multicenter single-arm, phase II study evaluated the efficacy and safety of uninterrupted panitumumab usage combined with cytotoxic doublets for unresectable/metastatic colorectal cancer (mCRC)."	( Multicenter, single-arm, phase II study of the continuous use of panitumumab in combination with FOLFIRI after FOLFOX for RAS wild-type metastatic colorectal cancer: Exploratory sequential examination of acquired mutations in circulating cell-free DNA. Akazawa, N; Ando, T; Hirata, K; Kagawa, Y; Kato, T; Maeda, H; Mishima, H; Nagasaka, T; Nagata, N; Oba, K; Sakamoto, J; Shiozawa, M; Watanabe, J; Yamada, T; Yokota, M, 2022)	0.72
" Topoisomerase-I inhibitor irinotecan is used clinically to treat colorectal cancer (CRC), often in combination with 5-fluorouracil (5FU)."	( ATM kinase inhibitor AZD0156 in combination with irinotecan and 5-fluorouracil in preclinical models of colorectal cancer. Bagby, SM; Cadogan, EB; Davis, SL; Diamond, JR; Durant, ST; Hartman, SJ; Hughes, GD; Leal, AD; Lieu, CH; Messersmith, WA; Pitts, TM; Schlaepfer, M; Simmons, DM; Tse, T; Yacob, BW, 2022)	0.72
" Immunoblotting results suggest an increase in DDR associated with irinotecan therapy, with a reduced effect noted when combined with AZD0156, which is more pronounced in some models."	( ATM kinase inhibitor AZD0156 in combination with irinotecan and 5-fluorouracil in preclinical models of colorectal cancer. Bagby, SM; Cadogan, EB; Davis, SL; Diamond, JR; Durant, ST; Hartman, SJ; Hughes, GD; Leal, AD; Lieu, CH; Messersmith, WA; Pitts, TM; Schlaepfer, M; Simmons, DM; Tse, T; Yacob, BW, 2022)	0.72
" This Phase I/II study examined the toxicity and efficacy of high-dose pulsed AZD8931, an EGFR/HER2/HER3 inhibitor, combined with chemotherapy, in metastatic colorectal cancer (CRC)."	( PANTHER: AZD8931, inhibitor of EGFR, ERBB2 and ERBB3 signalling, combined with FOLFIRI: a Phase I/II study to determine the importance of schedule and activity in colorectal cancer. Barber, PR; Forsyth, S; Gao, F; Hackett, LD; Hartley, JA; Hochhauser, D; Lopes, A; Lowe, HL; Ng, TT; Pearce, S; Propper, DJ; Sarker, D; Saunders, MP; Spanswick, VJ; Weitsman, GE; White, L, 2023)	0.91
" FOLFOX or FOLFIRI, each in combination with E+C, were the most active first-line treatments as compared with E+C or to chemotherapy alone."	( Antitumor Efficacy of Dual Blockade with Encorafenib + Cetuximab in Combination with Chemotherapy in Human BRAFV600E-Mutant Colorectal Cancer. Altucci, L; Anderson, A; Ciardiello, D; Ciardiello, F; Coker, O; De Falco, V; Della Corte, CM; Famiglietti, V; Fowlkes, NW; Kanikarla, P; Kopetz, S; Lee, HM; Martinelli, E; Martini, G; Morris, V; Napolitano, S; Sorokin, A; Tabernero, J; Troiani, T; Villareal, OE; Woods, M, 2023)	0.91
"To date, oxaliplatin and irinotecan are used in combination with 5-flourouracil (5-FU) for metastatic colorectal cancer."	( Radiosensitizing Effects of Irinotecan versus Oxaliplatin Alone and in Combination with 5-Fluorouracil on Human Colorectal Cancer Cells. Bock, F; Cappel, ML; Frerker, B; Hildebrandt, G; Klautke, G; Kriesen, S; Manda, K, 2023)	0.91

Bioavailability

Oral delivery of camptothecin has a treatment advantage but is limited by low bioavailability and gastrointestinal toxicity. The aqueous solubility of drug molecules is closely related to its bioactivity like bioavai.

Excerpt	Reference	Relevance
"7-fold that of parenteral administration, indicative of excellent oral bioavailability in the mouse."	( Comparative activity of oral and parenteral topotecan in murine tumor models: efficacy of oral topotecan. Johnson, RK; McCabe, FL, 1994)	0.29
" The drug is well absorbed from small intestine."	( [Topoisomerase inhibitors developing in Japan]. Furue, H, 1993)	0.29
" We determined the apparent bioavailability and pharmacokinetics of topotecan administered orally to 12 patients with solid tumours in a two-part crossover study."	( Bioavailability and pharmacokinetics of oral topotecan: a new topoisomerase I inhibitor. Beijnen, JH; Creemers, GJ; Davies, B; de Boer-Dennert, M; McDonald, M; Rosing, H; Schellens, JH; Verweij, J, 1996)	0.29
" The low bioavailability may be caused by hydrolysis of topotecan lactone in the gut, yielding substantial amounts of the open-ring form, which is poorly absorbed."	( Clinical pharmacokinetics of topotecan. Beijnen, JH; Herben, VM; ten Bokkel Huinink, WW, 1996)	0.29
" Recently bioavailability of an oral formulation of approximately 30% with limited variability was reported."	( Phase I and pharmacologic study of oral topotecan administered twice daily for 21 days to adult patients with solid tumors. Broom, C; Burris, HA; Creemers, GJ; Eckardt, JR; Gerrits, CJ; Hudson, I; Loos, WJ; Planting, AS; Rodriguez, GI; Schellens, JH; Verweij, J; Von Hoff, DD, 1997)	0.3
" After oral administration the bioavailability varied between 30 and 35%."	( [Topoisomerase I inhibitor with potential radiosensitizing effect]. Heuser, A; Sauer, R, 1997)	0.3
" The assays were developed to enable pharmacological analysis of 9AC in a bioavailability and oral phase I study in patients with solid tumors."	( Determination of the lactone and lactone plus carboxylate forms of 9-aminocamptothecin in human plasma by sensitive high-performance liquid chromatography with fluorescence detection. Loos, WJ; Nooter, K; Schellens, JH; Sparreboom, A; Stoter, G; Verweij, J, 1997)	0.53
" We performed a study with GI147211, a new semisynthetic camptothecin analogue, to determine the absolute bioavailability of the drug given orally."	( The bioavailability of oral GI147211 (GG211), a new topoisomerase I inhibitor. Creemers, GJ; de Boer-Dennert, M; DePee, S; Gerrits, CJ; Harteveld, M; Planting, AS; Pritchard, JF; Schellens, JH; Verweij, J; Wissel, P, 1997)	0.54
"We conclude that this formulation is not suitable for further clinical development because of poor bioavailability and highly variable and/or saturable absorption or elimination."	( Phase I clinical and pharmacokinetic study of oral 9-aminocamptothecin (NSC-603071). Fleming, GF; Iyer, L; Janisch, L; Mani, S; Ratain, MJ; Schilsky, RL; Wang, X, 1998)	0.54
" In view of this observation, the pharmacokinetics and oral bioavailability of 9-AC polyethylene glycol 1000 capsules were evaluated in 12 patients with solid tumors."	( Pharmacokinetics and bioavailability of oral 9-aminocamptothecin capsules in adult patients with solid tumors. de Jonge, MJ; Loos, WJ; Nooter, K; Porro, MG; Punt, CJ; Sparreboom, A; Verweij, J, 1998)	0.55
"Although topoisomerase inhibitors, such as camptothecin and topotecan, have been widely used in the treatment of nonglial tumors, their application for gliomas has been limited by poor efficacy relative to toxicity that may in part reflect limited bioavailability and blood stability of these agents."	( Potent topoisomerase I inhibition by novel silatecans eliminates glioma proliferation in vitro and in vivo. Bom, D; Burke, TG; Curran, DP; Erff, M; Pollack, IF; Strode, JT, 1999)	0.57
" Recently, a bioavailability of approximately 48% for the oral PEG-1000 formulation was reported."	( Phase I and pharmacologic study of oral (PEG-1000) 9-aminocamptothecin in adult patients with solid tumors. Dallaire, BK; de Jonge, MJ; Gelderblom, AH; Loos, WJ; Planting, AS; Punt, CJ; Sparreboom, A; van Beurden, V; van der Burg, ME; van Maanen, LW; Verweij, J; Wagener, DJ, 1999)	0.55
"0 mg/m2 over 5 min) was recently characterized in 12 patients in a bioavailability study."	( Role of erythrocytes and serum proteins in the kinetic profile of total 9-amino-20(S)-camptothecin in humans. Brouwer, E; Dallaire, BK; de Jonge, MJ; Gelderblom, HJ; Loos, WJ; Sparreboom, A; Verweij, J, 1999)	0.53
" Since typical substrates for intestinal carriers are hydrophilic and charged, the involvement of putative absorptive carriers in the transport of CPT is a novel finding that may give insight into the erratic oral bioavailability of CPTs observed in the clinic."	( The intestinal absorption of camptothecin, a highly lipophilic drug, across Caco-2 cells is mediated by active transporter(s). Gupta, E; Lallo, A; Luo, F; Ramanathan, S; Rubin, E; Sinko, P; Vyas, V, )	0.42
" The mean absorption rate was reduced to 89 +/- 16% of control in response to a sublethal 4 Gy TBI and dropped to 47."	( Nuclear scintigraphic assessment of intestinal dysfunction after combined treatment with 9-amino-20(S)-camptothecin (9-AC) and irradiation. Kirichenko, AV; Mason, K; Rich, TA; Straume, M; Teates, CD, 2000)	0.52
" Genetic polymorphisms of the UGT1A1 would affect an interindividual variation of the toxicity by irinotecan via the alternation of bioavailability of SN-38."	( Polymorphisms of UDP-glucuronosyltransferase gene and irinotecan toxicity: a pharmacogenetic analysis. Ando, M; Ando, Y; Hasegawa, Y; Muro, K; Saitoh, S; Saka, H; Sawa, T; Shimokata, K; Ueoka, H; Yokoyama, A, 2000)	0.31
"Irinotecan (CPT-11) is a camptothecin analog with low (about 10--20%) and variable oral bioavailability in animal models."	( Active transepithelial transport of irinotecan (CPT-11) and its metabolites by human intestinal Caco-2 cells. de Bruijn, P; de Jonge, MJ; Kurihara, M; Nishiyama, M; Sparreboom, A; Takano, H; Verweij, J; Yamamoto, W, 2001)	0.61
" These results may have therapeutic implications because the antitumor efficacy of ST1481 is in part related to a good bioavailability after oral administration, and the drug is currently under Phase I clinical evaluation."	( A novel 7-modified camptothecin analog overcomes breast cancer resistance protein-associated resistance in a mitoxantrone-selected colon carcinoma cell line. Beggiolin, G; Carenini, N; Carminati, P; De Cesare, M; De Isabella, P; Palumbo, M; Perego, P; Pezzoni, G; Pisano, C; Pratesi, G; Scheffer, GL; Tartaglia, L; Zunino, F, 2001)	0.64
" A rapid intestinal absorption and good oral bioavailability were supported by in vivo distribution studies, because the peak values of drug accumulation were found from 1 to 2 h after administration."	( Potent antitumor activity and improved pharmacological profile of ST1481, a novel 7-substituted camptothecin. Bucci, F; Capocasa, F; Carenini, N; Carminati, P; De Cesare, M; Merlini, L; Pace, S; Penco, S; Perego, P; Pisano, C; Pratesi, G; Tinelli, S; Vesci, L; Zunino, F, 2001)	0.53
" Efforts to further optimize therapeutic effectiveness through drug delivery strategies that prolong tumor exposure to these S phase-specific agents, such as improving oral bioavailability through structure modification and innovative formulation approaches, alternative parenteral dosage forms, and administration schedules, are being actively pursued."	( Current perspectives on the clinical experience, pharmacology, and continued development of the camptothecins. Garcia-Carbonero, R; Supko, JG, 2002)	0.53
" A cross-over design was chosen to determine the intrapatient variation of the bioavailability and pharmacokinetics of the anticancer agent depending on the timing of food intake in relation to the oral drug administration."	( Clinical phase II study and pharmacological evaluation of rubitecan in non-pretreated patients with metastatic colorectal cancer-significant effect of food intake on the bioavailability of the oral camptothecin analogue. Adank, S; Beijnen, JH; Botma, HJ; Ganser, A; Herr, A; Rosing, H; Schöffski, P; Van den Brande, J; Vermorken, JB; Volk, J; Wanders, J, 2002)	0.5
"The novel camptothecin derivative BNP1350 (7-[2-trimethylsilyl)ethyl]-20(S)-camptothecin), also known as Karenitecin, has been developed for superior oral bioavailability and increased lactone stability."	( Novel camptothecin derivative BNP1350 in experimental human ovarian cancer: determination of efficacy and possible mechanisms of resistance. Boven, E; Hausheer, FH; Pinedo, HM; Schlüper, HM; Van Hattum, AH, 2002)	1.2
" Pharmacokinetic and pharmacodynamic biomodulation, to enhance the bioavailability of the active anticancer agent or to reduce drug related toxicities have currently reached clinical application."	( Pharmacology of topoisomerase I inhibitors irinotecan (CPT-11) and topotecan. Loos, WJ; Mathijssen, RH; Sparreboom, A; Verweij, J, 2002)	0.31
" The absolute oral bioavailability of 9-NC was calculated to be 14."	( Pharmacokinetics of 9-nitro-20(S)-camptothecin in rats. Du, Y; Li, K; Xu, JH; Zhang, YF; Zhong, DF, 2003)	0.6
" The oral bioavailability of 9-NC was low."	( Pharmacokinetics of 9-nitro-20(S)-camptothecin in rats. Du, Y; Li, K; Xu, JH; Zhang, YF; Zhong, DF, 2003)	0.6
" Because the CPTs have poor bioavailability and are unable to cross the blood-brain barrier, they may best be delivered to the central nervous system by polymers."	( Camptothecin analogs in malignant gliomas: comparative analysis and characterization. Alderson, LM; Amundson, E; Brem, H; Colvin, M; Sampath, P; Tyler, BM; Wall, ME; Wani, MC; Weingart, JD, 2003)	1.76
" The mean bioavailability of total 9-ACCD was 68."	( Phase I and pharmacological study of oral 9-aminocamptothecin colloidal dispersion (NSC 603071) in patients with advanced solid tumors. Abbruzzese, JL; Madden, TL; Newman, RA; Tran, HT; Xiong, HQ, 2003)	0.57
" bolus was administered to assess the bioavailability of diflomotecan."	( Phase I pharmacological and bioavailability study of oral diflomotecan (BN80915), a novel E-ring-modified camptothecin analogue in adults with solid tumors. de Jonge, MJ; Devlin, M; Gelderblom, H; Obach, R; Pentheroudakis, G; Principe, P; Pruñonosa, J; Salazar, R; Seguy, F; Twelves, C; van Hooije, C; Verweij, J, 2003)	0.53
" The mean oral bioavailability (+/-SD) was 72."	( Phase I pharmacological and bioavailability study of oral diflomotecan (BN80915), a novel E-ring-modified camptothecin analogue in adults with solid tumors. de Jonge, MJ; Devlin, M; Gelderblom, H; Obach, R; Pentheroudakis, G; Principe, P; Pruñonosa, J; Salazar, R; Seguy, F; Twelves, C; van Hooije, C; Verweij, J, 2003)	0.53
"The purpose of the present study was to continue the investigation of the membrane transport mechanisms of 20-(S)-camptothecin (CPT) in order to understand the possible role of membrane transporters on its oral bioavailability and disposition."	( Membrane transport of camptothecin: facilitation by human P-glycoprotein (ABCB1) and multidrug resistance protein 2 (ABCC2). Guo, A; Lalloo, AK; Lee, SH; Luo, FR; Paranjpe, PV; Rubin, E; Sinko, PJ; Vyas, V, 2004)	0.85
" However, gefitinib treatment dramatically increased the oral bioavailability of irinotecan after simultaneous oral administration."	( Gefitinib enhances the antitumor activity and oral bioavailability of irinotecan in mice. Cheshire, PJ; Daw, N; Germain, GS; Gilbertson, R; Harwood, FC; Houghton, PJ; Jenkins, JJ; Leggas, M; Panetta, JC; Peterson, J; Schuetz, JD; Stewart, CF, 2004)	0.32
" Third, the coupling increases the bioavailability of CPT, induces apoptosis in tumor and, therefore, enhances anticancer activity of PEG-CPT."	( Antitumor activity of poly(ethylene glycol)-camptothecin conjugate: the inhibition of tumor growth in vivo. Borchard, G; Borowski, V; Chandna, P; Dharap, SS; Filpula, D; Mehlig, M; Minko, T; Peng, P; Wang, Y; Yang, K; Yu, D; Zhang, Z; Zhao, H, 2005)	0.59
" The absolute bioavailability of lactone and total 9-NC were calculated to be 23."	( Pharmacokinetics of lactone, carboxylate and total 9-nitrocamptothecin with different doses and administration routes in rats. Chen, J; Chu, X; Guo, J; Ping, Q; Song, M, 2006)	0.58
"The aim of this study was to examine whether a modulated radiofrequency of the type used in cellular phone communications at a specific absorption rate (SAR) higher than International Commission on Non-ionizing Radiation Protection (ICNIRP) reference level for occupational exposure, could elicit alterations on proliferation, differentiation, and apoptosis processes in a neuroblastoma cell line."	( Proliferation and apoptosis in a neuroblastoma cell line exposed to 900 MHz modulated radiofrequency field. Laconi, C; Lovisolo, GA; Marino, C; Merola, P; Negroni, A; Pinto, R, 2006)	0.33
"Rubitecan (RFS-2000, 9NC, Orathecin) is an orally bioavailable camptothecin analogue, with evidence of preclinical activity in colon cancer cell lines."	( Phase II study of rubitecan, an oral camptothecin in patients with advanced colorectal cancer who have failed previous 5-fluorouracil based chemotherapy. Auber, M; Cai, C; Kiefer, G; Matin, K; Patel, H; Potter, D; Ramanathan, RK; Schmotzer, A; Stoller, R; Zamboni, W, 2006)	0.85
" The pyrimidine analog trifluorothymidine (TFT) is part of the anti-cancer drug formulation TAS-102, which was developed to enhance the bioavailability of TFT in vivo, and is currently being evaluated as an oral chemotherapeutic agent in phase I clinical studies."	( Irinotecan-induced cytotoxicity to colon cancer cells in vitro is stimulated by pre-incubation with trifluorothymidine. Fukushima, M; Hoebe, EK; Peters, GJ; Temmink, OH, 2007)	0.34
" There was no significant difference between released and free drug for the area under the concentration-time curve (AUC) and bioavailability values."	( Biodistribution and pharmacokinetics of colon-specific HPMA copolymer--9-aminocamptothecin conjugate in mice. Gao, SQ; Kopecek, J; Kopecková, P; Lu, ZR, 2007)	0.57
"Gimatecan is an orally bioavailable camptothecin analogue with preclinical findings of promising antitumor activity."	( Concerted escalation of dose and dosing duration in a phase I study of the oral camptothecin gimatecan (ST1481) in patients with advanced solid tumors. Baselga, J; Capri, G; Carminati, P; Cerny, T; Cresta, S; D'Incalci, M; Gatti, B; Gianni, L; Hess, D; Malossi, A; Marsoni, S; Rota Caremoli, E; Sessa, C; Trigo, J; Zaniboni, A; Zanna, C; Zucchetti, M, 2007)	0.84
"Drug distribution in the gastrointestinal (GI) tract and the plasma concentration-time profile of 9-AC released from the HPMA copolymer conjugate were predicted using the degradation, transit, and absorption rate constants in cecum."	( Pharmacokinetic modeling of absorption behavior of 9-aminocamptothecin (9-AC) released from colon-specific HPMA copolymer-9-AC conjugate in rats. Gao, SQ; Kopecek, J; Kopecková, P; Peterson, CM; Sun, Y, 2008)	0.59
" They can be widely used to increase the cellular uptake, bioavailability and therapeutic efficacy, to optimize the biodistribution and intracellular release profile, and to reduce the systemic toxicity, clearance and degradation rate of non-covalently or covalently attached drugs."	( The effect of dendrimers on the pharmacodynamic and pharmacokinetic behaviors of non-covalently or covalently attached drugs. Cheng, Y; Xu, T, 2008)	0.35
" HPCT-PEG-NLC prolonged circulation time and increased bioavailability of HCPT."	( [Preparation of PEG-modified nanostructured lipid carriers loaded with hydroxycamptothecin and tissue distribution in mice]. Gan, L; Gan, Y; Nie, SF; Pan, WS; Yang, XG; Zhang, XX; Zhu, CL, 2008)	0.57
"9-Nitrocamptothecin (9-NC) is an orally administered topoisomerase-I inhibitor for the treatment of pancreatic carcinoma, but its oral absorption and bioavailability are poor."	( Self-microemulsifying drug delivery system (SMEDDS) improves anticancer effect of oral 9-nitrocamptothecin on human cancer xenografts in nude mice. Liu, XY; Lu, JL; Wang, JC; Zhang, Q; Zhang, X; Zhao, H; Zhao, SX; Zhou, SF, 2008)	1.02
"Studies suggest that complexation with PAMAM dendrimers has the potential to improve the oral bioavailability of SN-38."	( Potential oral delivery of 7-ethyl-10-hydroxy-camptothecin (SN-38) using poly(amidoamine) dendrimers. Ghandehari, H; Kolhatkar, RB; Swaan, P, 2008)	0.6
" The absolute bioavailability (F) of irinotecan control was 33%, which was increased to 43% (1."	( Pre-clinical evidence for altered absorption and biliary excretion of irinotecan (CPT-11) in combination with quercetin: possible contribution of P-glycoprotein. Awasthi, A; Bansal, T; Jaggi, M; Khar, RK; Talegaonkar, S, 2008)	0.35
"The bioavailability of belotecan and topotecan in rats was determined following oral administration of each drug at a dose of 5 mg/kg body weight."	( Involvement of P-glycoprotein, multidrug resistance protein 2 and breast cancer resistance protein in the transport of belotecan and topotecan in Caco-2 and MDCKII cells. Chung, SJ; Han, YH; Jin, HE; Kim, DD; Kim, W; Li, H; Shim, CK, 2008)	0.35
"The bioavailability of belotecan (11."	( Involvement of P-glycoprotein, multidrug resistance protein 2 and breast cancer resistance protein in the transport of belotecan and topotecan in Caco-2 and MDCKII cells. Chung, SJ; Han, YH; Jin, HE; Kim, DD; Kim, W; Li, H; Shim, CK, 2008)	0.35
"The involvement of secretory transporters P-gp, MRP2 and BCRP, particularly for belotecan, as well as a low passive permeability, appears to be responsible for the low bioavailability of belotecan and topotecan."	( Involvement of P-glycoprotein, multidrug resistance protein 2 and breast cancer resistance protein in the transport of belotecan and topotecan in Caco-2 and MDCKII cells. Chung, SJ; Han, YH; Jin, HE; Kim, DD; Kim, W; Li, H; Shim, CK, 2008)	0.35
" In the present study, irinotecan showed an absolute bioavailability of 30% as calculated from the pharmacokinetic data."	( Development and validation of reversed phase liquid chromatographic method utilizing ultraviolet detection for quantification of irinotecan (CPT-11) and its active metabolite, SN-38, in rat plasma and bile samples: application to pharmacokinetic studies. Awasthi, A; Bansal, T; Jaggi, M; Khar, RK; Talegaonkar, S, 2008)	0.35
" Diflomotecan has a high oral bioavailability (72 - 95%) and the oral day 1 - 5 every 3 weeks regimen is recommended for Phase II testing because it is relatively well tolerated, convenient and mimics protracted exposure."	( Diflomotecan, a promising homocamptothecin for cancer therapy. Gelderblom, H; Kroep, JR, 2009)	0.64
" These results indicated that CPT-loaded amphiphilic cyclodextrin nanoparticles might provide a promising carrier system for the effective delivery of this anticancer drug having bioavailability problems."	( Comparative evaluation of polymeric and amphiphilic cyclodextrin nanoparticles for effective camptothecin delivery. Bilensoy, E; Caliş, S; Cirpanli, Y; Lale Doğan, A, 2009)	0.57
" To assess the effect of gefitinib on the pharmacokinetics of IV irinotecan and on the bioavailability of a single oral dose of irinotecan."	( Tyrosine kinase inhibitor enhances the bioavailability of oral irinotecan in pediatric patients with refractory solid tumors. Crews, KR; Daw, NC; Furman, WL; Gajjar, AJ; Houghton, PJ; McCarville, MB; McGregor, LM; Navid, F; Panetta, JC; Rodriguez-Galindo, C; Santana, VM; Spunt, SL; Stewart, CF; Wu, J, 2009)	0.35
" Gefitinib significantly enhances the bioavailability of oral irinotecan."	( Tyrosine kinase inhibitor enhances the bioavailability of oral irinotecan in pediatric patients with refractory solid tumors. Crews, KR; Daw, NC; Furman, WL; Gajjar, AJ; Houghton, PJ; McCarville, MB; McGregor, LM; Navid, F; Panetta, JC; Rodriguez-Galindo, C; Santana, VM; Spunt, SL; Stewart, CF; Wu, J, 2009)	0.35
" A series of small molecule camptothecin derivatives have been developed that increase solubility, lactone stability and bioavailability to varying levels of success."	( Cancer therapies utilizing the camptothecins: a review of the in vivo literature. Simanek, EE; Venditto, VJ, 2010)	0.94
" If a substrate drug with oral bioavailability is equal to or less than 80%, an intravenous drug interaction study at low dose along with a few key oral drug interaction studies could be useful for achieving this objective with the aid of modeling and simulations."	( Ongoing challenges in drug interaction safety: from exposure to pharmacogenomics. Bai, JP, 2010)	0.36
" A new approach was developed for promoting drug bioavailability that has the potential to decrease the required dose and side effects, particularly for chemotherapeutic drugs with narrow therapeutic index."	( The development of a dense gas solvent exchange process for the impregnation of pharmaceuticals into porous chitosan. Barrett, A; Dehghani, F; Foster, NR; Ji, C; Poole-Warren, LA, 2010)	0.36
" Modulating the physical characteristics of the amphiphilic co-polymers via co-polymerization offers a facile method for controlling the bioavailability of anticancer drugs, ultimately increasing effectiveness and minimizing toxicity."	( Amphiphilic block co-polyesters bearing pendant cyclic ketal groups as nanocarriers for controlled release of camptothecin. Farach-Carson, MC; Gurski, LA; Jia, X; Pochan, DJ; Wang, X; Xu, X; Zhong, S, 2011)	0.58
" Treatment with PEO-PPO-PEO micelles resulted in prolonged circulation time in blood and increased bioavailability of CPT-11 and SN-38 (7-ethyl-10-hydroxycamptothecin)."	( Effect of poly (ethylene oxide)-poly (propylene oxide)-poly (ethylene oxide) micelles on pharmacokinetics and intestinal toxicity of irinotecan hydrochloride: potential involvement of breast cancer resistance protein (ABCG2). Gan, L; Gan, Y; Guo, S; Zhang, X; Zhu, C, 2010)	0.56
" Together these results show that PAMAM dendrimers have the potential to improve the oral bioavailability of potent anti-cancer drugs."	( G3.5 PAMAM dendrimers enhance transepithelial transport of SN38 while minimizing gastrointestinal toxicity. Ghandehari, H; Goldberg, DS; Swaan, PW; Vijayalakshmi, N, 2011)	0.37
" Its hydrochloride salt, 13a·HCl exhibited not only excellent water solubility (1049 μg/mL) but also a high oral bioavailability (57."	( Discovery of 4-anilinofuro[2,3-b]quinoline derivatives as selective and orally active compounds against non-small-cell lung cancers. Chen, YL; Chen, YW; Liang, CC; Lu, PJ; Tseng, CH; Tzeng, CC; Yang, CN; Yao, YC, 2011)	0.37
" So it supplied the possibility of improving oral bioavailability of HCPT when combining together admoveatur of P-gp inhibitor, CsA."	( [Pharmaceutical evaluation of hydroxycamptothecin nanosuspensions with the action of inhibiting P-gp]. He, ZG; Pu, XH; Qin, YM; Sun, J; Zhang, P; Zhang, X, 2011)	0.64
" The nanosuspension in this study could accelerate the oral absorption rate of HCPT, and make improving bioavailability of HCPT possible."	( [Study on pharmacokinetics of HCPT nanosuspensions with ability of inhibiting P-gp in rats after oral administration]. He, Z; Pu, X; Sun, J; Sun, Y; Wang, Y; Zhang, P, 2011)	0.37
"This study describes a nanoparticle assembly containing cyclodextrin-based polymer and camptothecin, resulting in increased bioavailability of camptothecin, an effective but toxic anti-cancer agent."	( Preclinical study of the cyclodextrin-polymer conjugate of camptothecin CRLX101 for the treatment of gastric cancer. Chen, L; Davis, M; Gaur, S; Wang, Y; Yen, T; Yen, Y; Zhou, B, 2012)	0.84
" Here we assessed factors that may influence its oral bioavailability in rats."	( Pharmacokinetic modeling to assess factors affecting the oral bioavailability of the lactone and carboxylate forms of the lipophilic camptothecin analogue AR-67 in rats. Adane, ED; Anderson, BD; Leggas, M; Liu, Z; Xiang, TX, 2012)	0.58
" A population PK model that simultaneously fitted to oral and intravenous data was used to estimate the bioavailability (F) and clearance of AR-67."	( Pharmacokinetic modeling to assess factors affecting the oral bioavailability of the lactone and carboxylate forms of the lipophilic camptothecin analogue AR-67 in rats. Adane, ED; Anderson, BD; Leggas, M; Liu, Z; Xiang, TX, 2012)	0.58
" Covariate analysis showed that the bioavailability of the lactone, but not its clearance, was dose dependent."	( Pharmacokinetic modeling to assess factors affecting the oral bioavailability of the lactone and carboxylate forms of the lipophilic camptothecin analogue AR-67 in rats. Adane, ED; Anderson, BD; Leggas, M; Liu, Z; Xiang, TX, 2012)	0.58
" Thus, the knowledge about the characteristic and site-specific expression of CES1 and CES2 in rat intestine will help to predict the oral bioavailability of ester prodrugs."	( Identification of carboxylesterases expressed in rat intestine and effects of their hydrolyzing activity in predicting first-pass metabolism of ester prodrugs. Gao, J; Liu, D; Liu, Y; Ren, X; Xu, Y; Zhang, C, 2011)	0.37
"We found that Oncofid-S was poorly absorbed after intraperitoneal injection, the estimated AUC0–72 being less than 2%."	( Pharmacokinetic profile of Oncofid-S after intraperitoneal and intravenous administration in the rat. Bettella, F; Campisi, M; Greco, MC; Navarra, P; Renier, D; Tringali, G, 2012)	0.38
"Here we have demonstrated that Oncofid-S administered intraperitoneally in the rat was poorly absorbed into the systemic circulation, even after the administration of an extremely high dose."	( Pharmacokinetic profile of Oncofid-S after intraperitoneal and intravenous administration in the rat. Bettella, F; Campisi, M; Greco, MC; Navarra, P; Renier, D; Tringali, G, 2012)	0.38
" Olaparib is an orally bioavailable inhibitor of PARP-1 and PARP-2 that has been tested in multiple clinical trials."	( The combination of olaparib and camptothecin for effective radiosensitization. Hareyama, M; Matsumoto, H; Matsumoto, Y; Miura, K; Sakata, K; Someya, M; Takahashi, A, 2012)	0.66
" However, the low water solubility and low bioavailability of everolimus have prevented its clinical development as an anticancer drug."	( Preparation and in vivo evaluation of liposomal everolimus for lung carcinoma and thyroid carcinoma. Iwase, Y; Maitani, Y, 2012)	0.38
"Vandetanib (an orally bioavailable VEGFR-2 and EGFR tyrosine kinases inhibitor) was combined at 100 mg, 200 mg, or 300 mg daily with standard dosed cetuximab and irinotecan (3+3 dose-escalation design)."	( Phase I study of cetuximab, irinotecan, and vandetanib (ZD6474) as therapy for patients with previously treated metastastic colorectal cancer. Abrams, TA; Ancukiewicz, M; Blaszkowsky, L; Chan, JA; Duda, DG; Elliott, M; Enzinger, PC; Goldstein, M; Jain, RK; Kulke, MH; Meyerhardt, JA; Regan, E; Schrag, D; Wolpin, BM; Zhu, AX, 2012)	0.38
" Bioavailability for bead-based delivery was double that for IV administration, which was attributed to reduced clearance of the drug when delivered by this route."	( Feasibility, safety and pharmacokinetic study of hepatic administration of drug-eluting beads loaded with irinotecan (DEBIRI) followed by intravenous administration of irinotecan in a porcine model. Chung, ST; Czuczman, P; Finnie, J; Foster, D; Holden, RR; Kuchel, T; Lewis, AL; Porter, S, 2013)	0.39
" Moreover, in vivo bioavailability of LP-MS was evaluated with conventional enteric microspheres (enteric MS) as reference."	( Novel pH-sensitive lipid-polymer composite microspheres of 10-hydroxycamptothecin exhibiting colon-specific biodistribution and reduced systemic absorption. Gan, L; Gan, Y; Gao, YP; Zhang, XX; Zhu, CL, 2013)	0.62
" These transporters are expressed site- and membrane-specifically in enterocytes, which affects the bioavailability of ingested substrate drugs."	( [Role of ABC efflux transporters in the oral bioavailability and drug-induced intestinal toxicity]. Yokooji, T, 2013)	0.39
"Irinotecan is a camptothecin derivative with low oral bioavailability due to active efflux by intestinal P-glycoprotein receptors."	( Nano scale self-emulsifying oil based carrier system for improved oral bioavailability of camptothecin derivative by P-Glycoprotein modulation. Negi, LM; Talegaonkar, S; Tariq, M, 2013)	0.96
"Oral delivery of camptothecin has a treatment advantage but is limited by low bioavailability and gastrointestinal toxicity."	( Poly(amido amine) dendrimers as absorption enhancers for oral delivery of camptothecin. Bartlett, K; Ghandehari, H; Hubbard, D; McGill, LD; Ray, A; Sadekar, S; Thiagarajan, G, 2013)	0.96
"15h and the bioavailability was 40 times higher than 10-HCPT injection."	( Development and application of a UPLC-MS/MS method for the pharmacokinetic study of 10-hydroxy camptothecin and hydroxyethyl starch conjugate in rats. Cai, C; Li, G; Ren, T; Tang, X, 2014)	0.62
"006), demonstrating that modulation of i2 levels meaningfully impacts drug bioavailability and cellular response."	( Dual roles for splice variants of the glucuronidation pathway as regulators of cellular metabolism. Bellemare, J; Guillemette, C; Roberge, J; Rouleau, M, 2014)	0.4
"38 h and the bioavailability was 40 times higher than the commercial 10-HCPT injection."	( Hydroxyethyl starch-10-hydroxy camptothecin conjugate: synthesis, pharmacokinetics, cytotoxicity and pharmacodynamics research. Cai, C; Li, G; Qi, Y; Tang, X, 2016)	0.72
" Though several lipophilic derivatives of CPT have shown interesting oral bioavailability in preclinical and clinical studies, only Topotecan has been approved for this route of administration."	( A promising camptothecin derivative: Semisynthesis, antitumor activity and intestinal permeability. Bermejo, M; Corma, A; Díaz Cabañas, MJ; García-Giménez, JL; Gonzalez-Alvarez, I; Gonzalez-Alvarez, M; Mangas-Sanjuán, V; Rodríguez-Berna, G, 2014)	0.78
"Camptothecin (CPT) is an effective anticancer agent against various cancers but the clinical application is limited because of its poor water solubility, low bioavailability and severe toxic side effects."	( Preparation of camptothecin-loaded targeting nanoparticles and their antitumor effects on hepatocellular carcinoma cell line H22. Liu, Z; Xiong, X; Yan, B; Yang, A; Zhou, M, 2016)	2.23
" Pharmacokinetic analysis confirms that co-administration of gefitinib increases irinotecan bioavailability leading to an increased SN-38 lactone systemic exposure."	( Phase I dose escalation and pharmacokinetic study of oral gefitinib and irinotecan in children with refractory solid tumors. Brennan, RC; Furman, W; Mao, S; McGregor, LM; Santana, V; Stewart, CF; Turner, DC; Wu, J, 2014)	0.4
"Our study aimed to develop an amorphous 9-nitrocamptothecin solid dispersion (9-NC-SD) using polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus(®)) for improving its oral bioavailability and antitumor efficacy in vivo."	( Soluplus(®) based 9-nitrocamptothecin solid dispersion for peroral administration: preparation, characterization, in vitro and in vivo evaluation. Dong, J; Fu, Y; Gong, T; Lian, X; Lin, Q; Teng, Y; Zhang, J, 2014)	0.96
"In addition, nanosuspension could increase bioavailability and intratumor accumulation of CPT in vivo after intravenous administration, and then produced a much higher antitumor effect and biocompatibility than that of CPT solution."	( Nanocarrier improves the bioavailability, stability and antitumor activity of camptothecin. Gao, JQ; Han, M; He, ZG; Shen, YQ; Tang, XJ; Xu, DH; Yang, B, 2014)	0.63
" Systemically administered drugs are often poorly bioavailable in the brain, and drug efficacy within the central nervous system can be limited by peripheral toxicity."	( Intravenous delivery of camptothecin-loaded PLGA nanoparticles for the treatment of intracranial glioma. Berens, ME; Chung, EP; Dhruv, HD; DiPerna, DM; Householder, KT; Sirianni, RW; Wohlleb, GM, 2015)	0.72
" Because the oral bioavailability of 5-FU is unpredictable and highly variable, 5-FU is commonly administered intravenously."	( Role of ABC transporters in fluoropyrimidine-based chemotherapy response. Magdy, T; Nies, AT; Schwab, M; Zanger, UM, 2015)	0.42
" Mouse oral bioavailability was complete (100%) with extensive tumor exposure."	( The clinical development candidate CCT245737 is an orally active CHK1 inhibitor with preclinical activity in RAS mutant NSCLC and Eµ-MYC driven B-cell lymphoma. Aherne, GW; Box, G; Boxall, KJ; Collins, I; De Haven Brandon, AK; Eccles, SA; Eve, PD; Garrett, MD; Hayes, A; Henley, AT; Hunter, JE; Lainchbury, M; Matthews, TP; McHardy, T; Osborne, J; Perkins, ND; Raynaud, FI; Reader, JC; Swales, K; Tall, M; Valenti, MR; Walton, MI, 2016)	0.43
" These nanodispersions have much increased bioavailability and thereby improved anti-cancer activities."	( Amphiphilic drugs as surfactants to fabricate excipient-free stable nanodispersions of hydrophobic drugs for cancer chemotherapy. Hu, S; Lee, DH; Lee, E; Li, X; Li, Y; Liu, X; Shen, Y; Tang, J; Wang, C; Wang, J; Zhou, Z, 2015)	0.42
" Lipid-based carriers are well-known for their ability to improve oral absorption and bioavailability of lipid soluble and highly permeable compounds."	( Lipophilic Prodrugs of SN38: Synthesis and in Vitro Characterization toward Oral Chemotherapy. Bala, V; Li, P; Prestidge, CA; Rao, S; Wang, S, 2016)	0.43
"ABT-751 is an orally bioavailable sulfonamide with antimitotic properties."	( Phase 1 Study of ABT-751 in Combination With CAPIRI (Capecitabine and Irinotecan) and Bevacizumab in Patients With Advanced Colorectal Cancer. Dasari, A; Donehower, RC; He, P; Hidalgo, M; Jimeno, A; Jin, R; Laheru, D; Messersmith, WA; Purcell, WT; Rudek, MA; Taylor, GE; Walker, R, 2016)	0.43
" This phase I study determined the MTD, dose-limiting toxicities (DLT), pharmacokinetics (PK), and pharmacodynamics (PD) of veliparib, an orally bioavailable PARP1/2 inhibitor, in combination with irinotecan."	( Phase I Safety, Pharmacokinetic, and Pharmacodynamic Study of the Poly(ADP-ribose) Polymerase (PARP) Inhibitor Veliparib (ABT-888) in Combination with Irinotecan in Patients with Advanced Solid Tumors. Bell, T; Boerner, JL; Boerner, SA; Bowditch, A; Burger, A; Cai, D; Chen, AP; Cleary, JM; Ferry-Galow, K; Heilbrun, LK; Ji, J; Kinders, RJ; Li, J; LoRusso, PM; Marrero, AM; Parchment, RE; Pilat, MJ; Rubinstein, L; Sausville, EA; Shapiro, GI; Smith, D; Tolaney, SM; Wolanski, A; Zhang, J; Zhang, Y, 2016)	0.43
" The CPT oral bioavailability was 7-fold higher than the value obtained with the control, whereas its clearance was significantly lower than for the aqueous suspension."	( Oral delivery of camptothecin using cyclodextrin/poly(anhydride) nanoparticles. Espuelas, S; He, B; Huarte, J; Irache, JM; Lai, Y; Tang, J, 2016)	0.77
"To investigate the effect of the particle size and coadministration of borneol on the pharmacokinetics and bioavailability of entrapped drug in different size poly(lactic-co-glycolic acid) (PLGA) nanoparticles."	( Effects of borneol on the pharmacokinetics of 9-nitrocamptothecin encapsulated in PLGA nanoparticles with different size via oral administration. Han, L; Li, R; Qing, J; Qiu, M; Ru, G; Sheng, J; Wang, J, 2016)	0.68
"The experiments showed that the encapsulation drug in nanoparticles with size below 200 nm could improve the oral bioavailability of 9-NC."	( Effects of borneol on the pharmacokinetics of 9-nitrocamptothecin encapsulated in PLGA nanoparticles with different size via oral administration. Han, L; Li, R; Qing, J; Qiu, M; Ru, G; Sheng, J; Wang, J, 2016)	0.68
" The combination of the two strategies provides a potential approach to improve the oral bioavailability of drug."	( Effects of borneol on the pharmacokinetics of 9-nitrocamptothecin encapsulated in PLGA nanoparticles with different size via oral administration. Han, L; Li, R; Qing, J; Qiu, M; Ru, G; Sheng, J; Wang, J, 2016)	0.68
" Irinotecan, a topoisomerase 1 inhibitor, has activity in these sarcomas, but due to poor bioavailability of its active metabolite (SN-38) has had limited clinical efficacy."	( STA-8666, a novel HSP90 inhibitor/SN-38 drug conjugate, causes complete tumor regression in preclinical mouse models of pediatric sarcoma. Baumgart, JT; Edessa, LD; Helman, LJ; Heske, CM; Lee, S; Mendoza, A; Neckers, L; Proia, DA; Trepel, J, 2016)	0.43
"Cell membrane permeability is an important determinant for oral absorption and bioavailability of a drug molecule."	( Highly predictive and interpretable models for PAMPA permeability. Jadhav, A; Kerns, E; Nguyen, K; Shah, P; Sun, H; Xu, X; Yan, Z; Yu, KR, 2017)	0.46
" Besides, compared to the SN-38 solution, SN-38/NCs-A had a higher bioavailability after intravenous injection; while the bioavailability of SN-38/NCs-B was even lower than that of the SN-38 solution."	( In vitro and in vivo evaluation of SN-38 nanocrystals with different particle sizes. Chen, M; Dong, Y; Gao, J; Hua, Y; Li, W; Li, Y; Zhang, H; Zhang, X; Zhao, L; Zheng, A, 2017)	0.46
"To improve the bioavailability of 10-hydroxycamptothecin, 10-hydroxycamptothecin solid dispersion(HCPT-SD) and 10-hydroxycamptothecin-phospholipid complex-solid dispersion(HCPT-PC-SD) were prepared, and their solubility and dissolution rate were evaluated in this study."	( [Comparison of bioavailability of two kinds of solid dispersion from 10-hydroxycamptothecin in SD rats in vivo]. Hao, HJ; Liu, YX; Song, XY; Wu, XC; Zhang, HQ; Zhang, YZ, 2016)	0.92
" However, the limited bioavailability of curcumin prevents its use for modulation of the function of these transporters in the clinical setting."	( Synthetic Analogs of Curcumin Modulate the Function of Multidrug Resistance-Linked ATP-Binding Cassette Transporter ABCG2. Ambudkar, SV; Chufan, EE; Fukuda, M; Ishida, M; Iwabuchi, Y; Kanehara, K; Kudoh, K; Murakami, M; Naitoh, T; Ohnuma, S; Shibata, H; Sugisawa, N; Unno, M, 2017)	0.46
"Fluorination is a well-known strategy for improving the bioavailability of bioactive molecules in the lead optimization phase of drug discovery projects."	( Design, semisynthesis and potent cytotoxic activity of novel 10-fluorocamptothecin derivatives. Goto, M; Hsu, PL; Lee, KH; Liu, YQ; Morris-Natschke, SL; Shang, XF; Song, ZL; Wang, MJ; Yang, CJ; Yang, QR; Zhang, XS, 2017)	0.69
" Further in vivo studies were carried out to analyze the biodistribution of the drug, blood biochemical analysis and bioavailability of the drug."	( Natural polymer functionalized graphene oxide for co-delivery of anticancer drugs: In-vitro and in-vivo. Andrews, NG; Deb, A; Raghavan, V, 2018)	0.48
"Irinotecan (IRN) (CPT-11) is a camptothecin derivative with low oral bioavailability due to active efflux by intestinal P-glycoprotein (p-gp) receptors."	( Improvement of oral efficacy of Irinotecan through biodegradable polymeric nanoparticles through in vitro and in vivo investigations. Ahmad, N; Ahmad, R; Alam, MA; Jalees Ahmad, F; Umar, S, 2018)	0.77
" Chitosan (CS)-coated-IRN-loaded-poly-lactic-co-glycolic acid (PLGA) nanoparticles (NPs) (CS-IRN-PLGA-NPs)in order to enhance oral bioavailability of IRN."	( Improvement of oral efficacy of Irinotecan through biodegradable polymeric nanoparticles through in vitro and in vivo investigations. Ahmad, N; Ahmad, R; Alam, MA; Jalees Ahmad, F; Umar, S, 2018)	0.48
"03 fold in Wistar rat's plasma as well as brain higher oral bioavailability through IRN-CS-PLGA-NPs when compared with IRN-S."	( Improvement of oral efficacy of Irinotecan through biodegradable polymeric nanoparticles through in vitro and in vivo investigations. Ahmad, N; Ahmad, R; Alam, MA; Jalees Ahmad, F; Umar, S, 2018)	0.48
"Camptothecin (CPT) is an important topoisomerase I enzyme (Topo I) targeting anti-cancer drug, but its oral administration is limited by poor bioavailability and severe side effects."	( Redox sensitive lipid-camptothecin conjugate encapsulated solid lipid nanoparticles for oral delivery. Du, Y; He, W; Ismail, M; Li, X; Ling, L; Xia, Q; Yao, C; Zhou, W, 2018)	2.24
"The lipophilic, orally bioavailable camptothecin analogue gimatecan is characterized by improved efficacy over conventional camptothecins on human tumor xenografts."	( High Efficacy of Intravenous Gimatecan on Human Tumor Xenografts. DE Cesare, M, 2018)	0.76
"CZ48, a prodrug of camptothecin (CPT) with derivative resistant to lactone hydrolysis, suffers from limited application for cancer treatment due to poor water-solubility, thus causing its low bioavailability and absorption in vivo."	( Optimal construction and pharmacokinetic study of CZ48-loaded poly (lactic acid) microbubbles for controlled drug delivery. Guo, SL; Li, SY, 2019)	0.84
" However, its application was terminated due to its low bioavailability and high toxicity."	( Transporter-Targeted Bile Acid-Camptothecin Conjugate for Improved Oral Absorption. Ding, Y; Li, Q; Xiao, L; Zhang, X; Zhou, Y, 2019)	0.8
"The ATP-binding cassette transporter P-glycoprotein (P-gp) is known to limit both brain penetration and oral bioavailability of many chemotherapy drugs."	( A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein. Ambudkar, SV; Brimacombe, KR; Chen, L; Gottesman, MM; Guha, R; Hall, MD; Klumpp-Thomas, C; Lee, OW; Lee, TD; Lusvarghi, S; Robey, RW; Shen, M; Tebase, BG, 2019)	0.51
"Drugs administration in whole-body circulation may lead to poorly bioavailable in central nervous system and often has toxic effects on peripheral tissues."	( Host immune response to anti-cancer camptothecin conjugated cyclodextrin-based polymers. Changou, CA; Chen, YF; Davis, ME; Lei, CS; Wang, YH; Yen, Y, 2019)	0.79
"The aqueous solubility of drug molecules is closely related to its bioactivity like bioavailability and subsequent therapeutic index, especially in the case of hydrophobic drugs like camptothecin (CPT), a potential broad-spectrum anti-cancer agent."	( Lytic peptide-grafted beta-cyclodextrin polymer based nano-scaled drug delivery system with enhanced camptothecin anti-cancer efficacy. Li, T; Liu, Y; Muhammad, N; Wang, J; Zhan, H; Zhao, H, 2020)	0.97
" In order to improve the bioavailability and prolong the treatment time of the 10-hydroxycamptothecin in vivo, we prepared 10-hydroxycamptothecin-tetrandrine liposome complexes with 10-hydroxycamptothecin as the basic anticancer drug, tetrandrine and liposomes as carriers."	( Pharmacokinetics of 10-hydroxycamptothecin-tetrandrine liposome complexes in rat by a simple and sensitive ultra-high performance liquid chromatography with tandem mass spectrometry. Mao, J; Ping, Y; Shuang, R; Wang, M; Zou, J, 2020)	1.07
"Chemotherapeutic drugs for colorectal cancer(CRC) which is currently the third most lethal cancer globally, are administered intravenously (iv) due to their low oral bioavailability resulting from their physicochemical properties."	( Cyclodextrin nanoparticle bound oral camptothecin for colorectal cancer: Formulation development and optimization. Aktaş, Y; Benito, JM; Bilensoy, E; Ünal, S, 2020)	0.83
" 10- Hydroxycamptothecin (10-HCPT) is a known anti-HCC agent but its poor solubility and bioavailability have limited its clinical use."	( Glycyrrhetinic Acid and TAT Peptide Modified Dual-functional Liposomes for Treatment of Hepatocellular Cancer. Huang, S; Li, M; Nie, X; Ren, D; Wang, Y; Wu, X; Yu, X, 2020)	0.94
"As a common method for postoperative adjuvant treatments of bladder tumor, chemotherapy encounters low tumor targeting, short tumor retention time and bad bioavailability in clinical applications, which result in unsatisfactory high chemotherapeutical doses, frequent administration and subsequent severe side effects."	( HCPT-peptide prodrug with tumor microenvironment -responsive morphology transformable characteristic for boosted bladder tumor chemotherapy. Ding, D; Gao, Z; Li, C; Liu, Q; Ou, H; Zeng, S; Zhang, J, 2021)	0.62
" The therapeutic effects of drug molecules are majorly dependent on the bioavailability and, in essence, on the solubility of the used drug molecules."	( Exploration on the drug solubility enhancement in aqueous medium with the help of endo-functionalized molecular tubes: a computational approach. Paul, R; Paul, S, 2021)	0.62
" These findings indicated that CPT-loaded polycationic CD nanoparticles could be an efficient oral nanocarrier formulation for anticancer molecules that have limited application because of oral bioavailability and stability problems."	( Therapeutic efficacy and gastrointestinal biodistribution of polycationic nanoparticles for oral camptothecin delivery in early and late-stage colorectal tumor-bearing animal model. Aktaş, Y; Benito, JM; Bilensoy, E; Bilgiç, E; Can Öztürk, S; Esendağlı, G; Korkusuz, P; Ünal, S; Yanık, H, 2021)	0.84
"Camptothecin (CPT) is a potent anticancer agent for the treatment of colorectal cancer; however, it exhibits some limitations, including poor solubility, low stability, and low bioavailability via oral administration, which restrict its usability in clinical treatments."	( A silica-based antioxidant nanoparticle for oral delivery of Camptothecin which reduces intestinal side effects while improving drug efficacy for colon cancer treatment. Li, N; Nagasaki, Y; Nguyen-Trinh, QN; Trinh, KXT; Trinh, NT; Vo, VT; Vong, LB, 2022)	2.41
" Various structural modifications in the A, B, C, D, and E-rings of the camptothecin molecule have been thoroughly studied to improve bioavailability and diminish toxicity."	( Total Synthesis, Mechanism of Action, and Antitumor Efficacy of Camptothecin and Some of its Analogues. Bacherikov, VA, 2022)	1.19
" Previous studies showed improved bioavailability and cytotoxicity of ginsenoside-modified nanostructured lipid carrier containing curcumin (G-NLC) in human colon cancer cell lines."	( Long-term Survival, Tolerability, and Safety of First-Line Bevacizumab and FOLFIRI in Combination With Ginsenoside-Modified Nanostructured Lipid Carrier Containing Curcumin in Patients With Unresectable Metastatic Colorectal Cancer. Baek, JH; Jeon, Y; Sym, SJ; Yoo, BK, )	0.13
"Fabrication of self-delivery drug systems can surmount low drug bioavailability and achieve a precise therapeutic process."	( Azide-Locked Prodrug Co-Assembly into Nanoparticles with Indocyanine Green for Chemophotothermal Therapy. Hou, M; Li, B; Li, Y; Liu, H; Liu, L; Xu, M; Xu, Z; Ye, M; Zhang, H, 2022)	0.72
" The efficacy of conventional CRC chemotherapy is hampered by poor drug solubility and bioavailability and suboptimal pharmacokinetic profiles."	( Oral delivery of camptothecin-loaded multifunctional chitosan-based micelles is effective in reduce colorectal cancer. Almeida, A; Castro, F; Lúcio, M; Resende, C; Sarmento, B; Schwartz, S, 2022)	1.06
" However, its poor solubility and low bioavailability limited the development of the drug."	( Preparation of a camptothecin analog FLQY2 self-micelle solid dispersion with improved solubility and bioavailability. Li, Q; Sun, X; Wang, H; Wang, W; Wang, Y; Yu, E; Zhuang, W, 2022)	1.06
"The successful preparation, pharmacokinetics, and pharmacodynamics studies of FLQY2-SD showed that the solubility and bioavailability of FLQY2 were improved, which facilitated the further druggability development of FLQY2."	( Preparation of a camptothecin analog FLQY2 self-micelle solid dispersion with improved solubility and bioavailability. Li, Q; Sun, X; Wang, H; Wang, W; Wang, Y; Yu, E; Zhuang, W, 2022)	1.06
"Design of nanovectors inspired by nature is a short cut to improve the efficacy and bioavailability of chemotherapeutic agents, while reduce the toxicity."	( Biomimetic nanoprodrugs from fatty acid modified camptothecin and albumin for enhanced pharmacotherapy. Gao, T; Liu, H; Xie, Z; Zheng, M, 2023)	1.16
"Camptothecin (CPT) is a potent chemotherapeutic agent for various cancers, but the broader application of CPT is still hindered by its poor bioavailability and systemic toxicity."	( Glutathione-Responsive Nanoparticles of Camptothecin Prodrug for Cancer Therapy. Gao, Y; Han, H; Liu, C; Lu, Y; Shang, K; Tang, L; Xie, J; Yu, C; Zhang, L; Zhu, L, 2023)	2.62
" However, the poor water solubility and bioavailability of SN38 constrained its clinical application."	( Synthesis and biological evaluation of novel SN38-glucose conjugate for colorectal cancer treatment. Chen, Y; Du, C; Jiang, X; Li, S; Luo, Y; Wang, Y; Wu, L; Xie, Y; Zhang, R, 2023)	0.91
" On the one hand, the low solubility of anticancer drugs may lead to a decrease in the absorption rate of anticancer drugs, poor treatment effect, and even death in severe cases."	( Study on the solubilization effect of 7-ethyl-10-hydroxycamptothecin based on molecular docking and molecular dynamics simulation. Gao, F; Guo, J; Li, X; Wang, T; Wu, M; Zhang, F, 2023)	1.16
" For lead optimization in new drug discovery stages, fluorination is an effective and robust approach to increase the bioavailability and optimize the pharmacokinetics of candidate compounds, thereby improving their efficacy."	( Improved anti-tumor activity of fluorinated camptothecin derivatives 9-fluorocamptothecin and 7-ethyl-9-fluorocamptothecin on hepatocellular carcinoma by targeting topoisomerase I. Bai, YP; Li, L; Liu, YQ; Luo, HB; Peng, LZ; Wang, ZP; Xu, CR; Yan, JX; Yang, CJ; Zhang, M; Zhang, ZJ; Zhu, LZ, 2023)	1.17
" This discovery suggests that PEPT1 has the potential to serve as a therapeutic target for both improving bioavailability and cancer-targeting treatment."	( Synthesis and biological activity assay of novel camptothecin-peptidic conjugates based on PEPT1. Hu, Z; Jing, L; Sui, D; Wang, S; Wang, Y; Zhang, Q; Zheng, J; Zhu, M; Zou, P, 2023)	1.16

Dosage Studied

An ultra-high performance liquid chromatography tandem mass spectrometry method for the analysis of 10-hydroxycamptothecin and tetrandrine in plasma has been developed, validated, and utilized to compare the pharmacokinetics of both drugs. The goal of this review is to summarize the relevant literature for others interested in the field of campsothecin-based therapeutics.

Excerpt	Relevance	Reference
" Bone marrow samples were taken 30 and 48 h post 0 h dosing in both the single and split dose studies."	( Micronucleus induction by camptothecin and amsacrine in bone marrow of male and female CD-1 mice. Holmström, M; Winters, V, 1992)	0.58
" in its dose-response relationship and in its time course for DNA synthesis."	( Characterization of a camptothecin-resistant human DNA topoisomerase I in an in vitro system for Simian virus 40 DNA replication. Andoh, T; Ishimi, Y; Nishizawa, M, 1991)	0.6
" The cumulative biliary and urinary excretion of radioactivity after dosage of rats with irinotecan were 62."	( Identification of the metabolites of irinotecan, a new derivative of camptothecin, in rat bile and its biliary excretion. Atsumi, R; Hakusui, H; Suzuki, W, 1991)	0.52
" CPT was found to reduce the level of immediate early viral mRNA in a dose-response manner."	( Role of DNA topoisomerase I in the replication of herpes simplex virus type 2. Maeno, K; Nishiyama, Y; Yamada, Y; Yamamoto, N, 1990)	0.28
" The responding patients were treated at a dosage of 100 mg/m2 or more."	( [A phase I study of weekly administration of CPT-11 in lung cancer]. Fukuoka, M; Furue, H; Hara, N; Hara, Y; Hasegawa, K; Negoro, S; Niitani, H; Taguchi, T, 1990)	0.28
" All of these drugs were able to induce rapid loss of dhfr gene dosage in the R500 cell population."	( Drug-induced loss of unstably amplified genes. Snapka, RM; Wani, MA, 1990)	0.28
" The irs2 mutant was found to be very similar in response to the A-T lines, showing a marked decrease in inhibition of DNA synthesis, compared to V79 cells, in both time-course and dose-response experiments."	( DNA-break repair, radioresistance of DNA synthesis, and camptothecin sensitivity in the radiation-sensitive irs mutants: comparisons to ataxia-telangiectasia cells. Ganesh, AN; Thacker, J, 1990)	0.53
" We observed that inhibitors of both type I and II topoisomerases induced high levels of sister chromatid exchanges at 10(-6) M, and that the dose-response curves of these drugs were very similar."	( Induction of sister chromatid exchanges by inhibitors of topoisomerases. Jacobson-Kram, D; Lim, M; Liu, LF; Williams, JR, 1986)	0.27
" These results strongly suggest that Bayesian estimation combined with only two optimally timed samples accurately predicts the AUC of CPT-11 and should be useful for implementing adaptive control dosing for monitoring CPT-11 systemic exposure in patients with cancer."	( Efficient sampling strategies for forecasting pharmacokinetic parameters of irinotecan (CPT-11): implication for area under the concentration-time curve monitoring. Arioka, H; Eguchi, K; Karato, A; Lieberman, R; Nakashima, H; Nomura, N; Ohmatsu, H; Shinkai, T; Shiraishi, J; Tamura, T, 1995)	0.29
" Total body clearance did not vary with increased dosage (mean = 14."	( Phase I and pharmacokinetic study of irinotecan (CPT-11) administered daily for three consecutive days every three weeks in patients with advanced solid tumors. Catimel, G; Chabot, GG; Clavel, M; Cote, C; Dumortier, A; Engel, C; Gouyette, A; Guastalla, JP; Mahjoubi, M; Mathieu-Boué, A, 1995)	0.29
" The steady-state concentrations of total drug will be measured in several of these trials to establish its potential role in adaptive dosing using this schedule."	( Clinical, pharmacokinetic and biological studies of topotecan. Frucht, H; Goosenberg, E; Haas, NB; Halbherr, T; LaCreta, FP; O'Dwyer, PJ; Yao, KS, 1994)	0.29
" Studies in our laboratory have shown that there are significant differences in the in vivo behavior of the two forms of camptothecin and that much higher plasma levels of the lactone form are present in rats after dosing with camptothecin (lactone) than after dosing with the sodium salt of the ring-opened camptothecin (carboxylate form)."	( Urinary and biliary disposition of the lactone and carboxylate forms of 20(S)-camptothecin in rats. Bindra, DS; Scott, DO; Stella, VJ; Sutton, SC, )	0.57
" Total drug steady-state plasma concentration provided a good estimate of neutropenia, suggesting a simple, easily monitored, pharmacokinetic parameter for adaptive dosing using this schedule."	( Phase I/pharmacokinetic study of topotecan by 24-hour continuous infusion weekly. Brennan, JM; Haas, NB; Hudes, GR; LaCreta, FP; O'Dwyer, PJ; Ozols, RF; Walczak, J, 1994)	0.29
"0-mg/m2 dosage level; thus, additional patients were treated with this dosage, followed by human recombinant granulocyte-colony stimulating factor (G-CSF)."	( Phase I study of topotecan for pediatric patients with malignant solid tumors. Bowman, L; Furman, W; Heideman, R; Kuttesch, JF; Marina, N; Ochs, J; Pratt, CB; Sandlund, JT; Santana, VM; Stewart, C, 1994)	0.29
" It was found that plasma concentrations and AUC values for the lactone were significantly higher after dosing with CPT than after dosing with Na-CPT."	( Plasma pharmacokinetics of lactone and carboxylate forms of 20(S)-camptothecin in anesthetized rats. Bindra, DS; Scott, DO; Stella, VJ, 1993)	0.52
" Intact lactone plasma levels achieved after dosing with the lactone form of CA and its 9-amino and 10,11-methylenedioxy derivatives exceeded the far less active carboxylate at all times."	( Pharmacokinetics of the 9-amino and 10,11-methylenedioxy derivatives of camptothecin in mice. Malspeis, L; Supko, JG, 1993)	0.52
" In combination therapy, half of the single dosage of each agent was used."	( Enhanced antitumor efficacy of a combination of CPT-11, a new derivative of camptothecin, and cisplatin against human lung tumor xenografts. Itoh, K; Kudoh, S; Kusunoki, Y; Masuda, N; Matsui, K; Morino, H; Nakagawa, K; Negoro, S; Takada, M; Takifuji, N, 1993)	0.52
" To clarify the pharmacokinetic difference between CPT-11 and SN-38, the plasma levels, tissue distribution and excretion of SN-38 were investigated after dosing rats with 14C-labeled SN-38."	( Pharmacokinetics of SN-38 [(+)-(4S)-4,11-diethyl-4,9-dihydroxy-1H- pyrano[3',4':6,7]-indolizino[1,2-b]quinoline-3,14(4H,12H)-dione], an active metabolite of irinotecan, after a single intravenous dosing of 14C-SN-38 to rats. Atsumi, R; Hakusui, H; Okazaki, O, 1995)	0.29
" Css was calculated for each patient; if it differed by more than 20% of target, a new dosage was begun within 6 hours."	( Escalating systemic exposure of continuous infusion topotecan in children with recurrent acute leukemia. Baker, SD; Evans, WE; Furman, WL; Pratt, CB; Rivera, GK; Stewart, CF, 1996)	0.29
" However, dosing guidelines for the administration of topotecan to patients with impaired hepatic function have not yet been established."	( Phase I and pharmacologic studies of topotecan in patients with impaired hepatic function. Bowling, K; Brubaker, A; Chen, TL; Donehower, RC; Ettinger, D; Forastiere, A; Grochow, LB; Ignacio, V; Lubejko, B; O'Reilly, S; Rowinsky, E; Sartorius, S; Slichenmyer, W; Smith, J, 1996)	0.29
" Because the concurrent administration of TPT and G-CSF resulted in severe myelosuppression at the lowest TPT dose level, an alternate posttreatment G-CSF schedule in which G-CSF dosing began after TPT (starting on day 6) was subsequently evaluated."	( Phase I and pharmacologic study of high doses of the topoisomerase I inhibitor topotecan with granulocyte colony-stimulating factor in patients with solid tumors. Bowling, MK; Donehower, RC; Grochow, LB; Kaufmann, SH; Peereboom, D; Rowinsky, EK; Sartorius, SE, 1996)	0.29
" The recommended dosage for phase II trial is 100 mg/m2 administered in 1 hour perfusion, every 21 days."	( [Taxotere (docetaxel) and CPT 11 (irinotecan): phase I trials]. Armand, JP; Couteau, C; Goncalves, E; Terret, C; Yakendji, K, 1996)	0.29
" The optimal dosage and schedule was 40 mg kg-1 daily for 5 days."	( Therapeutic activity of CPT-11, a DNA-topoisomerase I inhibitor, against peripheral primitive neuroectodermal tumour and neuroblastoma xenografts. Ardouin, P; Bénard, J; Bissery, MC; Boland, I; Bressac-de-Paillerets, B; Gouyette, A; Gyergyay, F; Morizet, J; Terrier-Lacombe, MJ; Vassal, G; Vénuat, AM, 1996)	0.29
" Further exploration of topotecan in pancreatic carcinoma using different dosing schedules is warranted."	( Phase II trial of topotecan in advanced or metastatic adenocarcinoma of the pancreas. Alexander, R; Amfoh, K; Engstrom, PF; Fox, S; Green, F; Kosierowski, R; Lusch, C; O'Dwyer, PJ; Raskay, B; Redei, I; Scher, RM, 1996)	0.29
" Neutropenia was the principal toxicity of topotecan on this dosing schedule."	( A phase II trial of topotecan in patients with previously untreated pancreatic cancer. Donehower, RC; Grochow, LB; O'Reilly, S; Ord, S; Rowinsky, EK, 1996)	0.29
" This review details the rationale for the dosage schedule of CPT-11 selected for phase II studies, based on the results of 3 European phase I dose-escalating trials in patients with solid tumours."	( Rationale for the dosage and schedule of CPT-11 (irinotecan) selected for phase II studies, as determined by European phase I studies. Abigerges, D; Armand, JP; Catimel, G; Clavel, M; Extra, YM; Marty, M, 1996)	0.29
"CPT-11 350 mg/m2 administered as an intravenous infusion once every 3 weeks was chosen for further evaluation in early phase II studies, since this dosage regimen allowed the highest dose intensity with the least toxicity and was convenient for outpatient use."	( Rationale for the dosage and schedule of CPT-11 (irinotecan) selected for phase II studies, as determined by European phase I studies. Abigerges, D; Armand, JP; Catimel, G; Clavel, M; Extra, YM; Marty, M, 1996)	0.29
" Further studies are ongoing to define the optimum dosage schedule for CPT-11 and to assess the utility of CPT-11 as a single agent in second-line therapy, or combined with 5-FU and other anticancer agents as first-line therapy."	( Current status of colorectal cancer: CPT-11 (irinotecan), a therapeutic innovation. Cunningham, D, 1996)	0.29
" A dose-response effect for CPT-11 activity has been noted in the human tumour cloning assay."	( Future directions for clinical research with CPT-11 (irinotecan). von Hoff, D, 1996)	0.29
" Studies are ongoing to define fully optimum dosage schedules of CPT-11/5-FU combinations, and some of these schedules will soon enter phase II and III clinical trials."	( CPT-11 (irinotecan) and 5-fluorouracil: a promising combination for therapy of colorectal cancer. Khayat, D; Saltz, L; Shimada, Y, 1996)	0.29
" Our goal was the development of dosing regimens optimal for chemotherapeutic activity of the drug."	( Pharmacokinetics of camptothecins administered orally. Ahmed, AE; Giovanella, BC; Liehr, JG, 1996)	0.62
" In replicate experiments, CPT-11 was given at a dosage of 40 mg/kg per dose via intraperitoneal injection in 10% dimethylsulfoxide on days 1-5 and 8-12, which is the dosage lethal to 10% of treated animals."	( Therapeutic efficacy of the topoisomerase I inhibitor 7-ethyl-10-(4-[1-piperidino]-1-piperidino)-carbonyloxy-camptothecin against pediatric and adult central nervous system tumor xenografts. Bigner, DD; Elion, GB; Friedman, HS; Hare, CB; Houghton, JA; Houghton, PJ; Keir, S; Marcelli, SL, 1997)	0.51
" Phase I trials found antitumor activity in many topotecan dosing schedules, one of which involved the administration of topotecan daily as a 30-minute infusion for 5 consecutive days, with the cycle repeated every 21 days."	( Efficacy and safety of topotecan in the treatment of advanced ovarian carcinoma. Armstrong, D; Carmichael, J; Gordon, A; Malfetano, J; ten Bokkel Huinink, W, 1997)	0.3
" Proliferation does not seem to be necessary for the effect of Topo, and no superiority for protracted dosing schedules was observed."	( Cytotoxic activity of topotecan in human tumour cell lines and primary cultures of human tumour cells from patients. Csóka, K; Dhar, S; Fridborg, H; Jonsson, E; Larsson, R; Nygren, P; Sundström, C, 1997)	0.3
" CPT-11 clearly retained its anti-tumor activity at a lower dosage (27 mg kg-1 day-1)."	( Potent therapeutic activity of irinotecan (CPT-11) and its schedule dependency in medulloblastoma xenografts in nude mice. Bissery, MC; Boland, I; Gouyette, A; Kalifa, C; Lellouch-Tubiana, A; Morizet, J; Sainte-Rose, C; Santos, A; Terrier-Lacombe, MJ; Vassal, G, 1997)	0.3
" A large number of phase I studies with topotecan have been conducted since 1992 in both adults and children with a broad range of refractory malignancies and as many as 14 different dosing schedules."	( Review of phase I clinical studies with topotecan. Rowinsky, EK; Verweij, J, 1997)	0.3
" Clinical studies with topotecan have not yielded as promising results, with response rates of approximately 7% to 10%, but modifications in dosing schedule or combinations with other agents may enhance antitumor activity."	( Topotecan in advanced colorectal cancer. Creemers, GJ, 1997)	0.3
" In addition, treatment with TJ-14 accelerated the healing of the intestinal tract injured by repeated dosing of CPT-11 and inhibited significantly the increase of colonic prostaglandin E2 (PGE2) which is closely related to the onset of diarrhea."	( Preventive effects of Hange-shashin-to on irinotecan hydrochloride-caused diarrhea and its relevance to the colonic prostaglandin E2 and water absorption in the rat. Aburada, M; Hayakawa, T; Kamataki, T; Kase, Y; Komatsu, Y, 1997)	0.3
" The lactone form of HCPT was detectable in various tissues examined up to 72 h after dosing at all the three test doses."	( Preclinical pharmacology of the natural product anticancer agent 10-hydroxycamptothecin, an inhibitor of topoisomerase I. Cai, Q; Chambless, B; Li, Y; Liu, T; Sun, H; Zhang, R, 1998)	0.53
" The dosing regimen recommended for Phase II trials of the 9AC CD formulation is 54."	( Phase I trial of the colloidal dispersion formulation of 9-amino-20(S)-camptothecin administered as a 72-hour continuous intravenous infusion. Bryant, M; Eder, JP; Kufe, DW; Lynch, T; Shulman, LN; Supko, JG; Vosburgh, E; Xu, G, 1998)	0.53
" The most common adverse events are well characterized and are reversible upon treatment discontinuation or dosage reduction."	( Irinotecan hydrochloride: drug profile and nursing implications of a topoisomerase I inhibitor in patients with advanced colorectal cancer. Berg, D, 1998)	0.3
" Phase I studies of irinotecan conducted in Europe, Japan and the US have provided useful information on optimal dosage and scheduling, as well as thorough evaluation of the toxicity profile of the drug."	( A risk-benefit assessment of irinotecan in solid tumours. Rowinsky, EK; Siu, LL, 1998)	0.3
" Raltitrexed, a thymidylate synthase inhibitor, offers similar antitumoral activity together with a tolerability in comparison to standard 5-fluorouracil based chemotherapy and its simple dosage schedule also contributes to better quality of life."	( [Drug clinics. How I treat. II. Therapeutic approaches to metastatic colorectal cancer]. Bours, V; Fillet, G; Jerusalem, G, 1998)	0.3
" Serial plasma samples were collected up to 55 h after dosing and analyzed for 9-AC by liquid chromatography."	( Pharmacokinetics and bioavailability of oral 9-aminocamptothecin capsules in adult patients with solid tumors. de Jonge, MJ; Loos, WJ; Nooter, K; Porro, MG; Punt, CJ; Sparreboom, A; Verweij, J, 1998)	0.55
" This review showed toxicities to be fairly consistent across dosing schedules, although the severity and extent of diarrhea and neutropenia differed somewhat."	( Irinotecan: a review of the initial phase I trials. Eckhardt, SG, 1998)	0.3
" These alternative dosing schedules may facilitate integration of irinotecan into combination chemotherapy and combined-modality treatment regimens."	( Alternative dosing schedules for irinotecan. Drengler, RL; Eckhardt, SG; Hammond, L; Kuhn, JG; Miller, LL; Petit, RG; Rothenberg, ML; Rowinsky, EK; Schaaf, LJ; Villalona-Calero, MA; Von Hoff, DD, 1998)	0.3
" The panel agreed that further data from a National Cancer Institute (NCI)-sponsored intergroup trial is required to determine the optimal dosage of octreotide and its cost in the treatment of cancer."	( Recommended guidelines for the treatment of chemotherapy-induced diarrhea. Benson, AB; Catalano, R; Engelking, C; Field, M; Kornblau, SM; Mitchell, E; Rubin, J; Trotta, P; Vokes, E; Wadler, S, 1998)	0.3
" Dosage and administration, status of clinical application, pharmacokinetics, pharmacodynamics and drug interactions are discussed."	( Clinical pharmacokinetics of camptothecin topoisomerase I inhibitors. Beijnen, JH; Herben, VM; Schellens, JH; Ten Bokkel Huinink, WW, 1998)	0.59
" Treatment-related side effects not only decrease the patient's quality of life, they also may compromise treatment efficacy by necessitating dosage reductions or interruptions in therapy."	( Managing the side effects of chemotherapy for colorectal cancer. Berg, D, 1998)	0.3
" Our hypothesis is that the camptothecins require a prolonged schedule of administration given continuously at low doses or frequent intermittent dosing schedules to be most effective."	( Camptothecins: a review of their development and schedules of administration. Muggia, FM; O'Leary, J, 1998)	2.04
" The observation that most tumor responses were seen at the highest doses administered in phase I trials suggest a dose-response relationship with this drug."	( [Irinotecan pharmacokinetics]. Canal, P; Chabot, GG; Lokiec, F; Robert, J, 1998)	0.3
" The present study demonstrates that 9NC selectively inhibits release of HIV-1 from freshly infected monocytoid U937 cells in a dose-response manner."	( 9-nitrocamptothecin selectively inhibits human immunodeficiency virus type 1 replication in freshly infected parental but not 9-nitrocamptothecin-resistant U937 monocytoid cells. Doniger, J; Hung, CL; Pantazis, P; Sadaie, MR, 1999)	0.76
"Grade 4 delayed diarrhea was the DLT at the 80 mg/m2/d dosage in patients younger than 65 years of age and at the 66 mg/m2/d dosage in patients 65 or older."	( Phase I and pharmacokinetic trial of oral irinotecan administered daily for 5 days every 3 weeks in patients with solid tumors. Drengler, RL; Elfring, GL; Hammond, LA; Hodges, S; Kraynak, MA; Kuhn, JG; Locker, PK; Miller, LL; Rodriguez, GI; Rothenberg, ML; Schaaf, LJ; Staton, BA; Stephenson, JA; Villalona-Calero, MA; Von Hoff, DD, 1999)	0.3
"The MTD and recommended phase II dosage for oral CPT-11 is 66 mg/m2/d in patients younger than 65 years of age and 50 mg/m2/d in patients 65 or older, administered daily for 5 days every 3 weeks."	( Phase I and pharmacokinetic trial of oral irinotecan administered daily for 5 days every 3 weeks in patients with solid tumors. Drengler, RL; Elfring, GL; Hammond, LA; Hodges, S; Kraynak, MA; Kuhn, JG; Locker, PK; Miller, LL; Rodriguez, GI; Rothenberg, ML; Schaaf, LJ; Staton, BA; Stephenson, JA; Villalona-Calero, MA; Von Hoff, DD, 1999)	0.3
" These results indicate that SLN are a promising sustained release and drug targeting system for lipophilic antitumour drugs, and may also allow a reduction in dosage and a decrease in systemic toxicity."	( Body distribution in mice of intravenously injected camptothecin solid lipid nanoparticles and targeting effect on brain. Cai, Y; Liang, BW; Lu, LF; Yang, CZ; Yang, SC; Zhu, JB, 1999)	0.55
" A modest increase in CPT dosage was possible by choosing the best tolerated time to administer the radiation sensitizer."	( Radiation enhancement by 9-aminocamptothecin: the effect of fractionation and timing of administration. Kirichenko, AV; Rich, TA, 1999)	0.59
"5 mg/m2/day dosing but was not cumulative."	( Phase I/pharmacokinetic study of the topoisomerase I inhibitor GG211 administered as a 21-day continuous infusion. DeMaria, D; Grochow, LB; Kaye, SB; McDonald, A; O'Dwyer, PJ; Paz-Ares, L; Selinger, K; Sludden, J; Stevenson, JP; Twelves, C; Wissel, P, 1999)	0.3
" Four patients were assigned to different dosage levels, and drug toxicity was evaluated for the first 2 cycles."	( Phase I study of a combination of irinotecan and ifosfamide in advanced primary lung cancer. Gohara, R; Ichiki, M; Kawayama, T; Kinoshita, M; Mitui, T; Oizumi, K; Okubo, Y; Rikimaru, T, 1999)	0.3
" The initial irinotecan dosage of 350 mg/m(2) every 3 weeks was modifiable according to toxicity."	( Results of a European Organization for Research and Treatment of Cancer/Early Clinical Studies Group phase II trial of first-line irinotecan in patients with advanced or recurrent squamous cell carcinoma of the cervix. Chauvergne, J; Chevallier, B; Dieras, V; Fargeot, P; Fumoleau, P; Krakowski, Y; Lentz, MA; Lhommé, C; Matthieu-Boué, A; Mignard, D; Misset, JL; Rebattu, P; Roche, H; Van Glabbeke, M; Vennin, P, 1999)	0.3
" The starting dosage was 12."	( Phase I and pharmacokinetic study of irinotecan administered as a low-dose, continuous intravenous infusion over 14 days in patients with malignant solid tumors. Beijnen, JH; Gruia, G; Herben, VM; Schellens, JH; Swart, M; ten Bokkel Huinink, WW; Vernillet, L, 1999)	0.3
" At a dosage of 10 mg/m(2)/d, 14-day administration resulted in grade 4 diarrhea in two of six patients and one episode of grade 4 vomiting occurred, whereas with 17-day administration, one episode of grade 3 nausea and two episodes of grade 3 or 4 diarrhea were observed in six patients."	( Phase I and pharmacokinetic study of irinotecan administered as a low-dose, continuous intravenous infusion over 14 days in patients with malignant solid tumors. Beijnen, JH; Gruia, G; Herben, VM; Schellens, JH; Swart, M; ten Bokkel Huinink, WW; Vernillet, L, 1999)	0.3
"The recommended dosage is 10 mg/m(2)/d for 14 days, repeated every 3 weeks."	( Phase I and pharmacokinetic study of irinotecan administered as a low-dose, continuous intravenous infusion over 14 days in patients with malignant solid tumors. Beijnen, JH; Gruia, G; Herben, VM; Schellens, JH; Swart, M; ten Bokkel Huinink, WW; Vernillet, L, 1999)	0.3
" In vitro experiments indicated that this phenomenon was associated with a substantial uptake of 9-AC lactone by erythrocytes immediately after dosing and its subsequent release followed by accumulation of 9-AC carboxylate in the plasma compartment mediated by a pH-dependent hydrolysis of the lactone form, which is unable to diffuse across cell membranes."	( Role of erythrocytes and serum proteins in the kinetic profile of total 9-amino-20(S)-camptothecin in humans. Brouwer, E; Dallaire, BK; de Jonge, MJ; Gelderblom, HJ; Loos, WJ; Sparreboom, A; Verweij, J, 1999)	0.53
" Each 50% inhibitory concentration was calculated based on the dose-response curves."	( Alteration of drug chemosensitivity caused by the adenovirus-mediated transfer of the wild-type p53 gene in human lung cancer cells. Hara, N; Nakanishi, Y; Osaki, S; Pei, XH; Takayama, K; Ueno, H, 2000)	0.31
" Previous studies demonstrated that drugs delivered to the respiratory tract in liposomal formulation resulted in high pulmonary drug concentration, reduced systemic toxicity, and reduced dosage requirements compared with parenteral and oral administration."	( 9-Nitrocamptothecin liposome aerosol treatment of melanoma and osteosarcoma lung metastases in mice. Gilbert, BE; Jia, SF; Kleinerman, ES; Knight, V; Koshkina, NV; Waidrep, C; Worth, LL, 2000)	0.76
" CPT-11 has been evaluated using a variety of dosing schedules."	( [CPT-11 (irinotecan)--evidence from molecular and pharmacological studies and clinical applications]. Ishikawa, N; Isobe, T; Oguri, T, 2000)	0.31
" The study design was based on the hypothesis that the non-overlapping toxicities of a 3-drug combination of irinotecan (Camptosar, CPT-11), carboplatin (Paraplatin), and paclitaxel (Taxol) would allow them to be dosed at recommended or standard doses, respectively."	( Phase I/II trial of irinotecan, carboplatin, and paclitaxel in advanced or metastatic NSCLC. Israel, VP; Miller, L; Natale, RB; Sandler, A; Socinski, M, 2000)	0.31
" The ongoing phase II portion of the study is restricted to previously untreated patients who will receive at least one cycle of either cisplatin or carboplatin in combination with etoposide followed by irinotecan at 60 mg/m2 and paclitaxel at 50 mg/m2 dosed once weekly for 3 weeks."	( Phase I/II study of weekly irinotecan and paclitaxel in patients with SCLC. Rushing, DA, 2000)	0.31
" We also showed that oral dosage with L-9NC had no detectable effect on cancer growth, and thus the benefit from aerosol treatment was due to pulmonary deposition and not the larger fraction of drug deposited in the nose of mice during aerosol treatment which is promptly swallowed."	( 9-Nitrocamptothecin liposome aerosol treatment of human cancer subcutaneous xenografts and pulmonary cancer metastases in mice. Gilbert, BE; Giovanella, BC; Kleinerman, ES; Knight, V; Koshkina, NV; Waldrep, JC, 2000)	0.76
" The plasma concentrations of lactone from 2 to 6 h after dosing were similar regardless of the form of DX-8951 administered."	( High-Performance liquid chromatographic analysis of lactone and hydroxy acid of new antitumor drug, DX-8951 (exatecan), in mouse plasma. Inukai, K; Konno, T; Nakaoka, M; Oguma, T; Yamada, M, 2001)	0.31
" Rats were dosed with the drug, and two major metabolites (UM-1 and UM-2) in the urine were isolated and purified by using ion-exchange column and HPLC."	( Urinary metabolites of DX-8951, a novel camptothecin analog, in rats and humans. Atsumi, R; Fujimaki, Y; Konno, T; Oguma, T; Okazaki, O; Yoshioka, N, 2001)	0.58
" Maximum tolerated dosage (MTD) for the topotecan and irinotecan combination was defined as that which permitted 4 weeks of topotecan and irinotecan administration with G-CSF at or near the dose intensity reported for each single agent."	( Phase I clinical trial of weekly combined topotecan and irinotecan. Lokich, J, 2001)	0.31
"To investigate the excretion of irinotecan hydrochloride (CPT-11) and its active metabolite, SN-38, into the gastrointestinal lumen via the biliary and/or intestinal membrane route after dosing with lactone and carboxylate forms of CPT-11, and to evaluate the toxic and antitumor effects of the two forms."	( Excretion into gastrointestinal tract of irinotecan lactone and carboxylate forms and their pharmacodynamics in rodents. Arimori, K; Kikuchi, M; Kumamoto, A; Kumazawa, E; Kuroki, N; Nakano, M; Tanoue, N; Tohgo, A, 2001)	0.31
" dosing (60 mg/kg) with CPT-11 lactone and carboxylate forms for 4 days."	( Excretion into gastrointestinal tract of irinotecan lactone and carboxylate forms and their pharmacodynamics in rodents. Arimori, K; Kikuchi, M; Kumamoto, A; Kumazawa, E; Kuroki, N; Nakano, M; Tanoue, N; Tohgo, A, 2001)	0.31
"The excretion of CPT-11 into bile was greater in dosing with CPT-11 carboxylate than that with its lactone form, whereas the exsorption across intestinal membrane was greater in dosing with CPT-11 lactone than that with its carboxylate form."	( Excretion into gastrointestinal tract of irinotecan lactone and carboxylate forms and their pharmacodynamics in rodents. Arimori, K; Kikuchi, M; Kumamoto, A; Kumazawa, E; Kuroki, N; Nakano, M; Tanoue, N; Tohgo, A, 2001)	0.31
"The decreased antitumor effect caused by dosing with the CPT-11 carboxylate form could be due to less accumulation in the tissue including tumor cells resulting from the rapid elimination of the form in the body."	( Excretion into gastrointestinal tract of irinotecan lactone and carboxylate forms and their pharmacodynamics in rodents. Arimori, K; Kikuchi, M; Kumamoto, A; Kumazawa, E; Kuroki, N; Nakano, M; Tanoue, N; Tohgo, A, 2001)	0.31
"0 mg/kg per dose via intraperitoneal injection for a period of 10 consecutive days, which is the dosage lethal to 10% of treated animals."	( Therapeutic activity of 7-[(2-trimethylsilyl)ethyl)]-20 (S)-camptothecin against central nervous system tumor-derived xenografts in athymic mice. Bigner, DD; Friedman, HS; Hausheer, F; Keir, ST; Lawless, AA, 2001)	0.55
"Regression models were developed based on data from a phase I clinical trial involving 34 patients with advanced solid tumor malignancies who received CPT-11 as a 90-min infusion on an every 3-week dosing schedule."	( Limited sampling models for CPT-11, SN-38, and SN-38 glucuronide. Atherton, P; Erlichman, C; Pitot, HC; Reid, J; Schaaf, L; Sloan, JA, 2001)	0.31
"To evaluate relationships between various body-size measures and irinotecan (CPT-11) clearance and metabolism in cancer patients, and to provide future dosing recommendations for this agent."	( Impact of body-size measures on irinotecan clearance: alternative dosing recommendations. de Jonge, MJ; Mathijssen, RH; Nooter, K; Sparreboom, A; Stoter, G; Verweij, J, 2002)	0.31
" These findings provide a rationale for the conduct of a comparative phase III study between BSA-based dosing and flat or fixed dosing of CPT-11."	( Impact of body-size measures on irinotecan clearance: alternative dosing recommendations. de Jonge, MJ; Mathijssen, RH; Nooter, K; Sparreboom, A; Stoter, G; Verweij, J, 2002)	0.31
"These results indicate that AUC-based dosing of carboplatin is still rational in combination chemotherapy."	( Phase I/II and pharmacologic study of irinotecan and carboplatin for patients with lung cancer. Ando, M; Ando, Y; Hasegawa, Y; Ikeda, T; Minami, H; Saka, H; Sakai, S; Sato, M; Sekido, Y; Shimokata, K; Watanabe, A; Yamamoto, M, 2001)	0.31
" The large variation in the UGT activity being related to the genetic status would warrant pharmacogenetic-guided dosing of irinotecan."	( Polymorphisms of UDP-glucuronosyltransferase and pharmacokinetics of irinotecan. Ando, Y; Hasegawa, Y; Ichiki, M; Shimokata, K; Sugiyama, T; Ueoka, H, 2002)	0.31
" Plasma samples were obtained during the first 24 hours after initial dosing to determine the total concentrations (lactone + carboxylate forms) of CPT-11; of the active metabolite SN-38; and of SN-38 glucuronide (SN-38G)."	( Phase I dose-finding and pharmacokinetic trial of irinotecan (CPT-11) administered every two weeks. Eckhardt, SG; Elfring, GL; Hammond, LA; Hodges, S; Kuhn, JG; Locker, PK; Miller, LL; Petit, RG; Rinaldi, DA; Rodriguez, GI; Rothenberg, ML; Schaaf, LJ; Sharma, A; Villalona-Calero, MA; von Hoff, DD, 2001)	0.31
" Prediction of the drug sensitivity of each patient and cell kill kinetics of the drug may improve the outcome of treatment and avoid unnecessary dosing of the drug."	( Prediction of cell kill kinetics of anticancer agents using the collagen gel droplet embedded-culture drug sensitivity test. Komiyama, M; Mori, T; Ohnishi, M; Okada, H; Tsutsui, A; Yabushita, H, )	0.13
" However, the optimum dosing schedule remains to be determined."	( Irinotecan hydrochloride for the treatment of recurrent and refractory non-Hodgkin lymphoma: a single institution experience. Aiba, K; Fujiwara, K; Horikoshi, N; Ito, Y; Mizunuma, N; Omachi, K; Saotome, T; Sugiyama, K; Takahashi, S, 2002)	0.31
" Efforts to further optimize therapeutic effectiveness through drug delivery strategies that prolong tumor exposure to these S phase-specific agents, such as improving oral bioavailability through structure modification and innovative formulation approaches, alternative parenteral dosage forms, and administration schedules, are being actively pursued."	( Current perspectives on the clinical experience, pharmacology, and continued development of the camptothecins. Garcia-Carbonero, R; Supko, JG, 2002)	0.53
" CPT-11 dosing (10 mg/kg), and bile samples were collected."	( Biliary transport of irinotecan and metabolites in normal and P-glycoprotein-deficient mice. Bingham, CM; Hossfeld, DK; Iyer, L; Mayer, U; Ramírez, J; Ratain, MJ; Shepard, DR, 2002)	0.31
" These results suggest that CPT-11 has activity against recurrent malignant glioma using a dosing regimen of 300 mg/m(2) every 3 weeks showing limited toxicity."	( Irinotecan treatment for recurrent malignant glioma using an every-3-week regimen. Cloughesy, TF; Elfring, GL; Filka, E; Friedman, H; Kabbinavar, F; Miller, LL; Nelson, G, 2002)	0.31
"25 mg kg(-1) per day) at one of six dosing times expressed in hours after light onset (3, 7, 11, 15, 19 or 23 hours after light onset)."	( Circadian optimisation of irinotecan and oxaliplatin efficacy in mice with Glasgow osteosarcoma. Bissery, MC; D'Attino, RM; Filipski, E; Garufi, C; Granda, TG; Lévi, F; Terzoli, E; Vrignaud, P, 2002)	0.31
" As a result, both the host tolerance and antitumor efficacy of 5-fluorouracil (5-FU) and oxaliplatin (L-OHP), like 30 other anticancer drugs, vary largely according to the dosing time in laboratory rodents."	( Chronotherapy of colorectal cancer. Giacchetti, S, 2002)	0.31
" Further detailed pharmacokinetic studies of irinotecan in patients receiving concomitant therapy with enzyme-inducing anticonvulsants are required so that rational dosing recommendations can be provided for this patient population."	( Influence of phenytoin on the disposition of irinotecan: a case report. Berg, S; Bernstein, M; Blaney, SM; Cherrick, I; Kuttesch, N; Murry, DJ; Salama, V, 2002)	0.31
" A median of 78%/75% of the planned dosage of CPT-11/cisplatin was delivered."	( Neoadjuvant chemotherapy with CPT-11 and cisplatin downstages locally advanced gastric cancer. Hayek, M; Hochster, H; Marcus, SG; Muggia, F; Newman, E; Potmesil, M; Sewak, S; Sorich, J; Yee, H, )	0.13
" In the second stage, which begins at the first instance of DLT, a two-parameter logistic dose-response model estimates the MTD from the DLT experience of all patients."	( Adaptive dose finding for phase I clinical trials of drugs used for chemotherapy of cancer. Potter, DM, 2002)	0.31
" infusion at a dosage of 20 mg/m(2)/day for 5 days of 2 consecutive weeks."	( Altered irinotecan pharmacokinetics in pediatric high-grade glioma patients receiving enzyme-inducing anticonvulsant therapy. Bowers, DC; Chintagumpala, MM; Crews, KR; Fouladi, M; Gajjar, A; Heideman, RL; Houghton, PJ; Jones-Wallace, D; Stewart, CF; Thompson, SJ, 2002)	0.31
" One patient receiving EIAs experienced grade 3 diarrhea when the dosage of irinotecan was increased to 60 mg/m(2)/day."	( Altered irinotecan pharmacokinetics in pediatric high-grade glioma patients receiving enzyme-inducing anticonvulsant therapy. Bowers, DC; Chintagumpala, MM; Crews, KR; Fouladi, M; Gajjar, A; Heideman, RL; Houghton, PJ; Jones-Wallace, D; Stewart, CF; Thompson, SJ, 2002)	0.31
" Serial plasma, urine, and feces samples were obtained up to 500 hours after dosing and analyzed for irinotecan, metabolites (7-ethyl-10-hydroxycamptothecin [SN-38], SN-38 glucuronide [SN-38G], and APC), and ketoconazole by high-performance liquid chromatography."	( Modulation of irinotecan metabolism by ketoconazole. de Bruijn, P; Kehrer, DF; Mathijssen, RH; Sparreboom, A; Verweij, J, 2002)	0.52
" Animals were observed for signs of pharmacologic and/or toxicologic effects three times on days of dosing and once daily on nondosing days."	( 9-nitrocamptothecin liposome aerosol: lack of subacute toxicity in dogs. Brayton, C; Gilbert, BE; Knight, V; Seryshev, A, 2002)	0.77
" Three of 7 (43%) patients treated with irinotecan 300 mg/m(2) and capecitabine 2,300 mg/d had course 1 dose-limiting toxicity (DLT) defining maximum tolerated dosage (MTD)."	( Phase I clinical trial of irinotecan with oral capecitabine in patients with gastrointestinal and other solid malignancies. Baker, C; Chun, HG; Fehn, K; Goel, S; Hoffman, A; Hopkins, U; Jhawer, M; Landau, L; Makower, D; Mani, S; Rajdev, L; Wadler, S, 2002)	0.31
"5 mg/kg on a schedule of two 5-day dosing cycles separated by 2 drug-free days."	( Preclinical activity of an i.v. formulation of rubitecan in IDD-P against human solid tumor xenografts. Chen, SF; Hollister, B; Mishra, A; Sands, H; Stoeckler, JD, 2002)	0.31
") dosing of MMI-166 at 200 mg/kg starting 1 day after tumor inoculation led to a significantly prolonged survival effect by inhibiting liver metastasis of C-1H tumor cells."	( Augmented anti-metastatic efficacy of a selective matrix metalloproteinase inhibitor, MMI-166, in combination with CPT-11. Hojo, K; Maekawa, R; Maki, H; Sawada, TY; Tanaka, H; Yoshioka, T, 2002)	0.31
" Evaluation of PG molecular weight, CPT loading, aqueous solubility, and CPT equivalent dosing with respect to in vivo antitumor potencies of various linked conjugates led to identification of a preferred conjugate composition."	( Synthesis and in vivo antitumor activity of poly(l-glutamic acid) conjugates of 20S-camptothecin. Baker, B; Bellamy, G; Bhatt, R; de Vries, P; Klein, P; Singer, JW; Tulinsky, J, 2003)	0.54
" The difference in plasma esterase activity between 0 hr and 20 hr after HU injection was regarded as the mechanism underlying the dosing time-dependent difference of the SN-38 concentration."	( Cell kinetics-dependent antitumor effect of irinotecan hydrochloride induced by the synchronizing effect of hydroxyurea: cell kinetics and dosing time. Akagi, T; Higuchi, S; Inoue, K; Ishizaki, T; Kage, Y; Makinosumi, T; Ohdo, S; Taguchi, Y; Ushinohama, K; Yamauchi, A; Yukawa, E, 2003)	0.32
" DX-8951f was significantly effective in a dose-response manner on the BxPC-3 primary tumor."	( Efficacy of camptothecin analog DX-8951f (Exatecan Mesylate) on human pancreatic cancer in an orthotopic metastatic model. Bouvet, M; Hoffman, RM; Moossa, AR; Nassirpour, R; Sun, FX; Tohgo, A; Yagi, S, 2003)	0.7
" The present nanoparticle formation is suggested as a possibly useful dosage form of irinotecan against solid tumor."	( Antitumor properties of irinotecan-containing nanoparticles prepared using poly(DL-lactic acid) and poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol). Machida, Y; Onishi, H, 2003)	0.32
"Since the oral L/M absorption test is useful for assessing the degree of mucosal damage and measurement of intestinal permeability, this analysis should be recommended to determine the optimum timing and the adequate dosage of the anticancer drug administration."	( Assessment of the intestinal permeability following postoperative chemotherapy for human malignant disease. Honda, M; Inutsuka, S; Korenaga, D; Kusumoto, H; Nagahama, S; Nozoe, T; Takesue, F; Yasuda, M, )	0.13
" Pharmacogenomics is the study of inherited differences in interindividual drug disposition and effects, with the goal of selecting the optimal drug therapy and dosage for each patient."	( Cancer pharmacogenomics: current and future applications. McLeod, HL; Watters, JW, 2003)	0.32
" Using the subrenal capsule assay (80 nude mice) (NM-SRCA), 9-AC was evaluated at both low and high dosage levels (0."	( Camptothecin analogues and vinblastine in the treatment of renal cell carcinoma: an in vivo study using a human orthotopic renal cancer xenograft. El-Galley, R; Keane, TE; Sun, C, )	1.57
" Clinical trials using weekly or every 3 weeks dosing of irinotecan have been completed."	( Irinotecan in the treatment of glioma patients: current and future studies of the North Central Cancer Treatment Group. Ames, M; Buckner, JC; Cha, S; Erlichman, C; Kaufmann, SH; Miller, LL; O'Fallon, JR; Reid, JM; Schaaf, LJ; Wright, K, 2003)	0.32
" For the 6 patients who received EIAs but whose SN-38 areas under the concentration-time curve (AUCs) on Day 1 were below clinically significant levels, irinotecan dosage was increased, and subsequent pharmacokinetic studies were performed."	( Effect of intrapatient dosage escalation of irinotecan on its pharmacokinetics in pediatric patients who have high-grade gliomas and receive enzyme-inducing anticonvulsant therapy. Bowers, DC; Chintagumpala, MM; Crews, KR; Gajjar, A; Jones-Wallace, D; Stewart, CF, 2003)	0.32
"7 microg x h/ml) of CPT-11 after dosing with or without activated charcoal."	( Influence of multiple dose activated charcoal on the disposition kinetics of irinotecan in rats. Balram, C; Cheung, YB; Lee, EJ; Zhou, QY, 2002)	0.31
" Rats were dosed with the drug, and the metabolites in the bile were isolated and collected by high-performance liquid chromatography using a gradient elution."	( Identification of the metabolites of 9-nitro-20(S)-camptothecin in rats. Chen, X; Li, K; Li, Y; Zhong, D, 2003)	0.57
" Because of unacceptable toxicity among the first 13 patients, dosing was reduced to docetaxel 40 mg/m2/d and irinotecan 100 mg/m2/d intravenously at 21-d intervals."	( A phase II trial of docetaxel and CPT-11 in patients with metastatic adenocarcinoma of the esophagus, gastroesophageal junction, and gastric cardia. Alberts, SR; Cha, SS; Goldberg, RM; Jatoi, A; Kardinal, CG; Mailliard, JA; Morton, RF; Nair, S; Rowland, KM; Sargen, D; Stella, PJ; Tirona, MT, 2002)	0.31
"A phase I study of carboplatin (Paraplatin) administered in two different dosing schedules (single dose every 4 weeks and weekly dosing) in combination with weekly irinotecan (CPT-11, Camptosar) was conducted in patients with relapsed or refractory advanced malignancies."	( Phase I. Trial of irinotecan plus carboplatin in two dose schedules. Burris, HA; Greco, FA; Hainsworth, JD; Jones, SF; Kuzur, ME; Miranda, FT; Raefsky, EA; White, MB; Willcutt, NT; Yardley, DA, 2003)	0.32
" For example, Abdelbasit and Plackett proposed an optimal design assuming that the dose-response relationship follows some specified linear models."	( Experimental design and sample size determination for testing synergism in drug combination studies based on uniform measures. Fang, HB; Houghton, PJ; Tan, M; Tian, GL, 2003)	0.32
" Consistent with a mechanistic link between migration and apoptosis, the dose-response for stimulation of migration on laminin was inversely proportional to apoptosis induction."	( Migrating glioma cells activate the PI3-K pathway and display decreased susceptibility to apoptosis. Beaudry, CE; Berens, ME; Demuth, T; Holz, DR; Joy, AM; Ponce, FA; Tran, NL, 2003)	0.32
" The dosage levels of TXT and CPT-11 were as follows: level 1, 30 mg/m(2) and 50 mg/m(2); level 2, 35 and 50 mg/m(2); level 3, 40 and 50 mg/m(2); level 4, 40 and 60 mg/m(2); and level 5, 50 and 60 mg/m(2)."	( Biweekly administration regimen of docetaxel combined with CPT-11 in patients with inoperable or recurrent gastric cancer. Gamoh, M; Kanamaru, R; Mitachi, Y; Saitoh, S; Sakata, Y; Sekikawa, K; Terashima, M; Yoshioka, T, 2003)	0.32
" However, three patients at level 3 could not continue treatment without a decrease in the dosage after the second cycle."	( Biweekly administration regimen of docetaxel combined with CPT-11 in patients with inoperable or recurrent gastric cancer. Gamoh, M; Kanamaru, R; Mitachi, Y; Saitoh, S; Sakata, Y; Sekikawa, K; Terashima, M; Yoshioka, T, 2003)	0.32
" A phase I trial of PG490-88 for solid tumors began recently and safety and optimal dosing data should accrue within the next 12 months."	( PG490-88, a derivative of triptolide, causes tumor regression and sensitizes tumors to chemotherapy. Chung, C; Fidler, JM; Gao, M; Li, K; Rosen, GD; Ross, JA; Wei, K, 2003)	0.32
" Dose-response curves were interpolated to provide 50% lethal concentrations (LC(50))."	( Ex vivo analysis of topotecan: advancing the application of laboratory-based clinical therapeutics. Evans, SS; Harper, SM; Nagourney, RA; Radecki, S; Sommers, BL, 2003)	0.32
" Clinical trials that include pharmacokinetic and pharmacodynamic studies may be the most efficient way to optimize the therapeutic efficacy of ifosfamide and define the dosing and scheduling."	( Antiblastic drug combinations with ifosfamide: an update. Badalamenti, G; Fulfaro, F; Gebbia, N; Russo, A; Valerio, MR, 2003)	0.32
" Patients with elevated AST, creatinine or prior pelvic radiation do not appear to have increased sensitivity to irinotecan, but the data are not adequate to support a specific dosing recommendation."	( A phase I and pharmacokinetic study of irinotecan in patients with hepatic or renal dysfunction or with prior pelvic radiation: CALGB 9863. Budman, D; Byrd, J; Enders Klein, C; Fleming, G; Hohl, R; Hollis, D; Kastrissios, H; Leichman, CG; Marshall, J; Ramirez, J; Ratain, MJ; Rosner, GL; Venook, AP; Villalona, M, 2003)	0.32
" No grade 3/4 hematological toxicities were manifested at any dosage level."	( Weekly docetaxel for patients with platinum/paclitaxel/irinotecan-resistant relapsed ovarian cancer: a phase I study. Hirano, T; Kubo, H; Masaki, K; Ogura, H; Taoka, H; Terauchi, F; Yamamoto, Y, 2003)	0.32
" Using a Topo I-deficient murine B lymphoma-derived subclone (P388-45/C) selected for its resistance to high dosage of the antitumor drug camptothecin, we show that Topo I depletion results in the hypophosphorylation of SR proteins and impairs exonic splicing enhancer (ESE)-dependent but not constitutive splicing."	( Altered serine/arginine-rich protein phosphorylation and exonic enhancer-dependent splicing in Mammalian cells lacking topoisomerase I. Dupon, C; Gabut, M; Kohlhagen, G; Pommier, Y; Soret, J; Stévenin, J; Tazi, J, 2003)	0.52
" The purpose of this study was to investigate the efficacy, toxicity, and proper dosage of TUOXI as single agent in treatment of advanced and recurrent solid tumors."	( [Preliminary study of lyophilized 10-hydroxycamptothecin in advanced or recurrent malignancies]. Chen, Q; Guan, ZZ; He, YJ; Hu, XH; Huang, HQ; Jiang, WQ; Li, YH; Lin, XB; Lin, Z; Liu, KF; Shen, WX, 2003)	0.58
" HCPT was given at the dosage of 6-8 mg/m(2) x d for 5-10 consecutive days based on the toxicity."	( [Preliminary study of lyophilized 10-hydroxycamptothecin in advanced or recurrent malignancies]. Chen, Q; Guan, ZZ; He, YJ; Hu, XH; Huang, HQ; Jiang, WQ; Li, YH; Lin, XB; Lin, Z; Liu, KF; Shen, WX, 2003)	0.58
" And the recommended dosage is 6-8 mg/m(2) as 4 hours infusion for 5-10 consecutive days every 3 weeks."	( [Preliminary study of lyophilized 10-hydroxycamptothecin in advanced or recurrent malignancies]. Chen, Q; Guan, ZZ; He, YJ; Hu, XH; Huang, HQ; Jiang, WQ; Li, YH; Lin, XB; Lin, Z; Liu, KF; Shen, WX, 2003)	0.58
" There was a moderate-to-fair relationship between CPT-11 dose and the area under the curve (AUC) for CPT-11 and APC over the 2, but no relationship dosage range of 350 to 800 mg/m between CPT-11 dose and the AUC for SN-38 or SN-38G."	( Phase 1 trial of irinotecan (CPT-11) in patients with recurrent malignant glioma: a North American Brain Tumor Consortium study. Chang, SM; Cloughesy, TF; Fine, HA; Fink, KL; Greenberg, HS; Hess, KR; Jaeckle, KA; Junck, L; Kuhn, J; Mehta, MP; Nicholas, MK; Prados, MD; Robins, HI; Schiff, D; Wen, PY; Yung, WK, 2004)	0.32
" In this article, a minimal pharmacokinetic-pharmacodynamic model is presented, based on a system of ordinary differential equations that link the dosing regimen of a compound to the tumor growth in animal models."	( Predictive pharmacokinetic-pharmacodynamic modeling of tumor growth kinetics in xenograft models after administration of anticancer agents. Cammia, C; Croci, V; De Nicolao, G; Germani, M; Magni, P; Pesenti, E; Poggesi, I; Rocchetti, M; Simeoni, M, 2004)	0.32
"The purpose is to evaluate the feasibility and safety of aerosol administration of the topoisomerase I inhibitor, 9-nitrocamptothecin, in a liposome formulation, and to recommend a dosage for a Phase II trial for an 8-week daily treatment schedule."	( Clinical evaluation of the delivery and safety of aerosolized liposomal 9-nitro-20(s)-camptothecin in patients with advanced pulmonary malignancies. Gilbert, BE; Huaringa, A; Knight, V; Loyer, E; Newman, RA; Verschraegen, CF; Walsh, G, 2004)	0.75
" Patients were treated with escalating doses of irinotecan with interval-modulated dosing of R115777 (continuously or on days 1-14, and repeated every 21 days)."	( Phase I and pharmacokinetic study of irinotecan in combination with R115777, a farnesyl protein transferase inhibitor. de Bruijn, P; de Heus, G; de Jonge, MJ; Eskens, FA; Kehrer, DF; Klaren, A; Mathijssen, RH; Palmer, PA; Planting, AS; Sparreboom, A; Verhaeghe, T; Verheij, C; Verweij, J; Xie, R; Zhang, S, 2004)	0.32
" Additional methods, including potential application of pharmacogenetic information, are needed to optimize irinotecan dosing and tailor therapy to individual patients."	( Relationship of baseline serum bilirubin to efficacy and toxicity of single-agent irinotecan in patients with metastatic colorectal cancer. Fuchs, CS; Kwok, A; McGovren, JP; Meyerhardt, JA; Ratain, MJ, 2004)	0.32
" IC(50) values were calculated from dose-response relationships using cell counts and a formazan dye assay (WST-1)."	( Cytotoxic activity of camptothecin and paclitaxel in newly established continuous human medullary thyroid carcinoma cell lines. Hamilton, G; Kaczirek, K; Mittlböck, M; Niederle, B; Passler, C; Pfragner, R; Prager, G; Raderer, M; Scheuba, C; Schindl, M; Siegl, V; Weinhäusel, A, 2004)	0.64
" These data indicate that the involvement of ATM following treatment with Topo poisons differs extensively with dosage and for different cell cycle checkpoints."	( Topoisomerase poisons differentially activate DNA damage checkpoints through ataxia-telangiectasia mutated-dependent and -independent mechanisms. Arooz, T; Chow, JP; Ho, HT; Lau, A; Poon, RY; Siu, WY, 2004)	0.32
" On the other hand, biliary excretion of CPT-11 and SN-38 was greater after dosing with the CPT-11 carboxylate form than that after the CPT-11 lactone form."	( Biliary excretion of irinotecan and its metabolites. Hirano, T; Iseki, K; Itagaki, S; Itoh, T; Sasaki, K; Takemoto, I, 2004)	0.32
" The starting dosage of CPT-11 was 15 mg/m2 per day (days 1-3 and 8-10), and dosage-escalation increments of 5 mg/m2 per day were planned, with fixed dosages of carboplatin (250 mg/m2 per day, day 1) and dexamethasone (40 mg/body, days 1-3 and days 8-10)."	( Phase I study of the combination of irinotecan hydrochloride, carboplatin, and dexamethasone for the treatment of relapsed or refractory malignant lymphoma. Maeda, K; Okamura, S; Shibuya, T; Suzumiya, J; Suzushima, H; Tamura, K; Utsunomiya, A, 2004)	0.32
"To determine the in vitro drug sensitivity of two non-small-cell lung cancer cell lines after treatment with the novel lipophilic camptothecin derivative, 7- tert-butyldimethylsilyl-10-hydroxycamptothecin (DB-67), to determine if topoisomerase I protein levels decrease after treatment with DB-67, and to assess the duration and extent of topoisomerase I modulation after DB-67 exposure, in order to provide information about drug resistance that may be useful in determining an appropriate dosing schedule for DB-67."	( The effect of DB-67, a lipophilic camptothecin derivative, on topoisomerase I levels in non-small-cell lung cancer cells. Adams, VR; Bence, AK; Burke, TG; Mattingly, CA, 2004)	0.81
" Dosing DB-67 once every 48-72 h may maximize the interaction of the drug with topoisomerase I and should be considered as a potential dosing schedule in the preclinical and clinical development of this compound."	( The effect of DB-67, a lipophilic camptothecin derivative, on topoisomerase I levels in non-small-cell lung cancer cells. Adams, VR; Bence, AK; Burke, TG; Mattingly, CA, 2004)	0.6
" Using different schedules and dosing durations, gimatecan exhibited an acceptable toxicity profile, with myelotoxicity being the dose-limiting toxic effect."	( Gimatecan, a novel camptothecin with a promising preclinical profile. Beretta, GL; Pratesi, G; Zunino, F, 2004)	0.65
"These findings suggest that flat-fixed dosing of irinotecan does not result in increased pharmacokinetic/pharmacodynamic variability and could be safely used to supplant current dosing strategies based on BSA."	( Flat-fixed dosing of irinotecan: influence on pharmacokinetic and pharmacodynamic variability. de Jong, FA; Mathijssen, RH; Sparreboom, A; Verweij, J; Xie, R, 2004)	0.32
" Dosage was reduced at any time if toxicity NCI CTC grade III/IV was observed."	( Irinotecan plus folinic acid/continuous 5-fluorouracil as simplified bimonthly FOLFIRI regimen for first-line therapy of metastatic colorectal cancer. Adami, B; Galle, PR; Heike, M; Hohl, H; Höhler, T; Klein, O; Moehler, M; Schroeder, M; Siebler, J; Steinmann, S; Teufel, A; Zanke, C, 2004)	0.32
" Dosing 9NC on a mg/m(2) basis does not reduce pharmacokinetic variability."	( Phase I and pharmacologic study of intermittently administered 9-nitrocamptothecin in patients with advanced solid tumors. Agarwala, SS; Belani, CP; Egorin, MJ; Fakih, M; Friedland, DM; Jin, R; Jung, LL; Potter, DM; Ramanathan, RK; Strychor, S; Troetschel, M; Trump, DL; Vozniak, M; Wong, MM; Zamboni, WC, 2004)	0.56
" In this regard results of preclinical studies have clearly pointed to the enhanced antitumor activity from protracted dosing of topoisomerase I interactive agents and results of clinical trials are now supporting these preclinical findings."	( Topoisomerase I interactive agents. Iacono, LC; Stewart, CF; Turner, PK, 2003)	0.32
" The survival curves differed significantly as a function of the dosage and circadian time of drug administration by the D1-10 schedule, with 70% survival at 7 or 11 HALO and 51% at 19 or 23 HALO (p=0."	( Circadian rhythm of irinotecan tolerability in mice. Filipski, E; Lemaigre, G; Lévi, F; Liu, XH; Mahjoubi, M; Méry-Mignard, D, 2004)	0.32
" Thirty-two patients with advanced refractory cancers (median age 64, 19 male) received 190 treatment courses at five dosing levels of irinotecan: 30 mg/m2 (n=6 patients), 60 (n=3), 90 (n=7), 120 (n=8) and 105 (n=8)."	( Biweekly administration of 24-h infusion of irinotecan followed by a 1-h infusion of docetaxel: a phase I study. Briasoulis, E; Fountzilas, G; Pavlidis, N; Pentheroudakis, G; Rammou, D; Timotheadou, H, 2004)	0.32
" The cytotoxic activity of irofulven is augmented when combined with agents that interact with DNA topoisomerase I; however, none of the reported studies have used the protracted dosing schedule found to be active clinically in treatment of childhood cancers."	( Enhanced antitumor activity of irofulven in combination with irinotecan in pediatric solid tumor xenograft models. Billups, C; Bjornsti, MA; Houghton, PJ; Liang, H; Peterson, JK; Woo, MH, 2005)	0.33
" We develop a maximum likelihood method based on the expectation/conditional maximization (ECM) algorithm to estimate the dose-response relationship while accounting for the informative censoring and the constraints of model parameters."	( Repeated-measures models with constrained parameters for incomplete data in tumour xenograft experiments. Fang, HB; Houghton, PJ; Tan, M; Tian, GL, 2005)	0.33
" A low dosage of BAI was administered by using CPT-11 (40 mg/m2) + CDDP (40 mg/m2) as one shot, and was repeated (three and six times respectively) for the two cases."	( [Evaluation of bronchial arterial infusion (BAI) for metastatic lung tumor from colorectal cancer]. Hayashi, N; Koshiishi, H; Koshiishi, Y; Okamura, T; Takahashi, E; Tamamoto, F; Yoshimura, T, 2004)	0.32
" The first group was given tailored CPT-11, adjusting individual optimal dosage using toxicity-based grading as an index in combination with TS-1, and the second group was given standard TS-1 treatment."	( [A randomized phase II clinical trial of tailored CPT-11 + TS-1 vs TS-1 in patients with advanced or recurrent gastric carcinoma as the first-line chemotherapy (JFMC31-0301)]. Kitajima, M; Kubota, T; Mai, M; Saji, S; Sakamoto, J; Takahashi, Y; Takeuchi, T; Toge, T, 2004)	0.32
" The marked improvement in toxicity and tolerance with vitamin supplementation suggests the need to reexamine optimal dosing in pemetrexed combination schedules."	( Pemetrexed in advanced colorectal cancer. de Gramont, A; Louvet, C, 2004)	0.32
" During the first cycle, grade 3 delayed diarrhea and grade 3 fever were the DLTs at the dosage of 80 mg/m(2)/day in three out of five patients."	( Phase I pharmacokinetic, food effect, and pharmacogenetic study of oral irinotecan given as semisolid matrix capsules in patients with solid tumors. Assadourian, S; de Jong, FA; de Jonge, MJ; Dumez, H; Eskens, FA; Lefebvre, P; Sanderink, GJ; Selleslach, J; Soepenberg, O; Sparreboom, A; Ter Steeg, J; Thomas, J; van Oosterom, AT; van Schaik, RH; Verweij, J, 2005)	0.33
" This study assessed the optimal dosing strategy for irinotecan, along with treatment efficacy and safety."	( Optimisation of irinotecan dose in the treatment of patients with metastatic colorectal cancer after 5-FU failure: results from a multinational, randomised phase II study. Bleiberg, H; Borner, M; Dirix, L; Gonzalez Baron, M; Gruia, G; Joosens, E; Morant, R; Roth, A; Sibaud, D; Van Belle, S; Van Cutsem, E; Van Laethem, JL, 2005)	0.33
"First, we determined the optimal dosing regimen in murine models."	( Sequential treatment with irinotecan and doxifluridine: optimal dosing schedule in murine models and in a phase I study for metastatic colorectal cancer. Fujimoto-Ouchi, K; Kato, T; Kikkawa, N; Mishima, H; Nishisho, I; Tanaka, Y; Tsujie, M; Tsujinaka, T; Yanagisawa, M, 2005)	0.33
" Morbidity is a significant limitation of this procedure, usually related to the extent of surgery, and hematological toxicity, which is considered as dependent upon the chemotherapy dosage alone."	( Impact of the extent and duration of cytoreductive surgery on postoperative hematological toxicity after intraperitoneal chemohyperthermia for peritoneal carcinomatosis. Boige, V; Elias, D; Estphan, G; Laplanche, A; Malka, D; Pocard, M; Raynard, B, 2005)	0.33
" Thus, the visual and chemical compatibility of irinotecan and epirubicin in the same infusion solution were investigated using both reference standards and pharmaceutical dosage forms."	( Spectrophotometric investigation of the chemical compatibility of the anticancer drugs irinotecan-HCl and epirubicin-HCl in the same infusion solution. Anilanmert, B; Ozdemir, FA; Pekin, M, 2005)	0.33
" Dose-response and time course assays for the drug camptothecin were obtained for comparison with conventional fluorometric detection."	( Homogeneous assays for cellular proteases employing the platinum(II)-coproporphyrin label and time-resolved phosphorescence. Hynes, J; O'Riordan, TC; Papkovsky, DB; Ponomarev, GV; Yashunski, D, 2005)	0.58
" The carboplatin dosage was calculated by using the Chatelut formula."	( A phase I study and pharmacologic evaluation of irinotecan and carboplatin for patients with advanced ovarian carcinoma who previously received platinum-containing chemotherapy. Fujiwara, Y; Kasamatsu, T; Katsumata, N; Tsunematsu, R; Yamada, T; Yamamoto, N; Yonemori, K, 2005)	0.33
" Pharmacologic studies demonstrated that administration of the dosage estimated with the Chatelut formula instead of the Chatelut formula with adjustment for serum creatinine resulted in a slightly excessive dose of carboplatin."	( A phase I study and pharmacologic evaluation of irinotecan and carboplatin for patients with advanced ovarian carcinoma who previously received platinum-containing chemotherapy. Fujiwara, Y; Kasamatsu, T; Katsumata, N; Tsunematsu, R; Yamada, T; Yamamoto, N; Yonemori, K, 2005)	0.33
" With a standard dose of paclitaxel at 135 mg m(-2), the dosage of irinotecan was escalated at four levels: 75, 100, 125 and 150 mg m(-2); 125 mg m(-2) was established as the maximum tolerated dose; this dosage was administered to 46 patients."	( Front-line paclitaxel and irinotecan combination chemotherapy in advanced non-small-cell lung cancer: a phase I-II trial. Antoniou, D; Armenaki, O; Dimitroulis, J; Grigoratou, T; Katis, C; Marosis, C; Michalopoulou, P; Stathopoulos, GP; Stathopoulos, J; Tsavdaridis, D, 2005)	0.33
" Only BILT significantly influenced the pharmacokinetics but this effect was not considered as relevant for dosing adjustment."	( Pharmacokinetic modelling of 5-FU production from capecitabine--a population study in 40 adult patients with metastatic cancer. Lokiec, F; Rezaí, K; Urien, S, 2005)	0.33
" We investigated efficacy and safety of the weekly dosing schedule of irinotecan."	( The safety and efficacy of the weekly dosing of irinotecan for platinum- and taxanes-resistant epithelial ovarian cancer. Andoh, M; Fujiwara, Y; Katsumata, N; Kohno, T; Matsumoto, K; Shimizu, C; Yamanaka, Y; Yonemori, K, 2006)	0.33
"The weekly dosing schedule of irinotecan seems to be effective and safe salvage chemotherapy regimen for platinum- and taxanes-resistant or refractory epithelial ovarian cancer."	( The safety and efficacy of the weekly dosing of irinotecan for platinum- and taxanes-resistant epithelial ovarian cancer. Andoh, M; Fujiwara, Y; Katsumata, N; Kohno, T; Matsumoto, K; Shimizu, C; Yamanaka, Y; Yonemori, K, 2006)	0.33
" In the high 5-FU group, seven of 14 patients (50%) received < or =80% of the planned chemotherapy dose during the first cycle due to dosage reductions whilst treatment delays occurred in 10/14 patients."	( Cetuximab and irinotecan/5-fluorouracil/folinic acid is a safe combination for the first-line treatment of patients with epidermal growth factor receptor expressing metastatic colorectal carcinoma. Folprecht, G; Köhne, CH; Lutz, MP; Nolting, A; Pollert, P; Schöffski, P; Seufferlein, T, 2006)	0.33
" Patients received CPT-11 and mitomycin-c at the dosage of 150 mg/m2 on days 1 and 15, and 8 mg/m2 on day 1, respectively, every 4 weeks."	( Irinotecan (CPT-11) and mitomycin-C (MMC) as second-line therapy in advanced gastric cancer: a phase II study of the Gruppo Oncologico dell' Italia Meridionale (prot. 2106). Battaglia, C; Colucci, G; Di Bisceglie, M; Gebbia, N; Gebbia, V; Giuliani, F; Maiello, E; Molica, S; Vinciarelli, G, 2005)	0.33
" Eventually, this may help to truly individualize the dosing of this (and other) anti-cancer agent(s), using a personal genetic profile of the most relevant enzymes for every patient."	( Role of pharmacogenetics in irinotecan therapy. de Jong, FA; de Jonge, MJ; Mathijssen, RH; Verweij, J, 2006)	0.33
" We have demonstrated from a rat model that intestinal beta-glucuronidase may play a key role in the development of CPT-11-induced delayed diarrhea by the deconjugation of the luminal SN-38 glucuronide, and the elimination of the intestinal microflora by antibiotics or dosing of TJ-14, a Kampo medicine that contains beta-glucuronidase inhibitor baicalin, exerted a protective effect."	( Optimal antidiarrhea treatment for antitumor agent irinotecan hydrochloride (CPT-11)-induced delayed diarrhea. Hagiwara, T; Kamataki, T; Kumazawa, E; Nagai, E; Onose, S; Takasuna, K; Watanabe, K; Yoshida, S, 2006)	0.33
" The treatment schedule modification, omitting the 5-FU dosing on day 8, considerably improved treatment compliance, reducing the incidence of febrile neutropenia, diarrhea, and asthenia."	( Irinotecan, oxaliplatin plus bolus 5-fluorouracil and low dose folinic acid every 2 weeks: a feasibility study in metastatic colorectal cancer patients. Bas, C; Bella, S; Chacon, M; Coppola, F; Escobar, E; Hidalgo, J; Korbenfeld, E; Martin, C; Martinez, J; Reale, M; Richardet, E; Senna, S; Smilovich, AM; Wasserman, E, 2006)	0.33
"Irinotecan hydrochloride (CPT-11), a topoisomerase I inhibitor highly effective for various cancers, has its dosage limited by diffuse mucosal damage with increased prostaglandin (PG) E(2)."	( Phospholipid fatty acid composition and diamine oxidase activity of intestinal mucosa from rats treated with irinotecan hydrochloride (CPT-11) under vegetable oil-enriched diets: comparison between perilla oil and corn oil. Aoyama, M; Fueda, Y; Kishimoto, K; Miyoshi, M; Ohata, A; Ohmae, K; Usami, M, )	0.13
" The effects of different multiple dosing schedules on tumor growth of LS174T colon carcinoma xenografts are elucidated."	( Preclinical efficacy of the camptothecin-polymer conjugate IT-101 in multiple cancer models. Bartlett, DW; Cheng, J; Davis, ME; Heidel, JD; Hollister, B; Hwang, J; Schluep, T, 2006)	0.63
" The purpose of this study was to investigate the efficacy, toxicity and proper dosage of 10-HCPT as a single agent by oral administration in the treatment of human colon cancer."	( Anticancer effects of low-dose 10-hydroxycamptothecin in human colon cancer. Chi, CW; Ho, LK; Lee, HC; Lee, JY; Lu, MF; Ping, YH; Wang, JJ; Wu, PH, 2006)	0.6
" The recommended dosage was set at 460 mg/m2 in 2 l/m2 of peritoneal instillation."	( Heated intra-operative intraperitoneal oxaliplatin alone and in combination with intraperitoneal irinotecan: Pharmacologic studies. Bonnay, M; Elias, D; Pocard, M; Raynard, B, 2006)	0.33
" A reduction in irinotecan dosage or use of an alternative agent may be warranted in patients with risk factors for toxicity."	( Individualizing chemotherapeutic treatment of colorectal cancer. Crews, KR, 2006)	0.33
" Extended dosing has met with early favourable results."	( Exploiting the role of O6-methylguanine-DNA-methyltransferase (MGMT) in cancer therapy. Middleton, MR; Sabharwal, A, 2006)	0.33
" However, the FDA decided that evidence indicates sufficient benefit to warrant informing prescribers, pharmacists and patients of the availability of pharmacogenetic tests and their possible role in the selection and dosing of these anticancer agents."	( TPMT, UGT1A1 and DPYD: genotyping to ensure safer cancer therapy? Maitland, ML; Ratain, MJ; Vasisht, K, 2006)	0.33
" Fixing synergistic drug ratios in pharmaceutical carriers provides an avenue by which anticancer drug combinations can be optimized prospectively for maximum therapeutic activity during preclinical development and differs from current practice in which dosing regimens are developed empirically in late-stage clinical trials based on tolerability."	( Ratiometric dosing of anticancer drug combinations: controlling drug ratios after systemic administration regulates therapeutic activity in tumor-bearing mice. Bally, MB; Harasym, NL; Harasym, TO; Janoff, AS; Johnstone, SA; Mayer, LD; Ramsay, EC; Shew, CR; Tardi, PG, 2006)	0.33
"The marked variability of irinotecan (Ir) clearance warrants individualized dosing based on hepatic drug handling."	( Relationship of hepatic functional imaging to irinotecan pharmacokinetics and genetic parameters of drug elimination. Clarke, SJ; Di Iulio, J; Ellis, A; Foo, K; Gurtler, V; Hicks, RJ; Hoskins, JM; Jefford, M; Michael, M; Milner, AD; Mitchell, PL; Scott, AM; Tebbut, NC; Thompson, M; Zalcberg, JR, 2006)	0.33
" Based on the results of our previous phase I/II study in patients with gastric cancer, the dosage was established in consideration of safety for outpatient therapy."	( [Irinotecan plus oral S-1 in patients with advanced colorectal cancer--biweekly IRIS regimen]. Asaka, M; Komatsu, Y; Kudo, M; Tateyama, M; Yuki, S, 2006)	0.33
"In this study, we attempted to determine the efficacy and toxicity of decreasing dosage of irinotecan plus 5-fluorouracil (5-FU) and leucovorin (LV) in the treatment of advanced colorectal cancer."	( Decreasing dosage of irinotecan, 5-flurouracil (5-FU) and leucovorin (LV) in the treatment of advanced and/or metastatic colorectal cancer: a phase II study. Chueh, TC; Huang, JS; Lai, CH; Lan, YJ; Liaw, CC; Wang, CH; Yen, CL; You, YT, )	0.13
"Twenty patients with rectal cancer (clinical Stage uT3-T4 or N+) received a standard dosing regimen of cetuximab (400 mg/m(2) on Day 1 and 250 mg/m(2) on Days 8, 15, 22, and 29) and escalating doses of irinotecan and capecitabine according to phase I methods: dose level I, irinotecan 40 mg/m(2) on Days 1, 8, 15, 22, and 29 and capecitabine 800 mg/m(2) on Days 1-38; dose level II, irinotecan 40 mg/m(2) and capecitabine 1000 mg/m(2); and dose level III, irinotecan 50 mg/m(2) and capecitabine 1000 mg/m(2)."	( Phase I trial of cetuximab in combination with capecitabine, weekly irinotecan, and radiotherapy as neoadjuvant therapy for rectal cancer. Dinter, D; Grobholz, R; Heeger, S; Hochhaus, A; Hofheinz, RD; Horisberger, K; Kähler, G; Kraus-Tiefenbacher, U; Post, S; Wenz, F; Willeke, F; Woernle, C, 2006)	0.33
" Gemcitabine alone was dosed at 1,000 mg/m2 up to 7 weeks in the first cycle, then once a week for the first 3 weeks of a 4-week cycle."	( Randomized phase III study of exatecan and gemcitabine compared with gemcitabine alone in untreated advanced pancreatic cancer. Abou-Alfa, GK; Ackerman, J; De Jager, RL; Eckhardt, SG; Feit, K; Harker, G; Hurwitz, H; Letourneau, R; Modiano, M; O'Reilly, EM; Tchekmedyian, NS, 2006)	0.33
" To better understand the biological importance of these two proteins, we performed a genotoxic screen on mouse embryonic stem (ES) cells impaired for either Brca2 or Blm to establish their genotoxic profiles (a cellular dose-response to a wide range of agents)."	( Embryonic stem cells deficient for Brca2 or Blm exhibit divergent genotoxic profiles that support opposing activities during homologous recombination. Hasty, P; Kim, TM; Marple, T, 2006)	0.33
" Although in a recently reported, randomized trial it was found that a regimen of irinotecan once every 3 weeks was associated with a lower incidence of severe diarrhea than with weekly treatment with similar efficacy, there is no evidence in the literature that suggests the optimal dosing strategy for the drug, along with treatment efficacy and safety, following 5-fluorouracil/oxaliplatin-based chemotherapy in elderly patients."	( Single-agent irinotecan as second-line weekly chemotherapy in elderly patients with advanced colorectal cancer. Cordio, S; Rosati, G, )	0.13
" Irinotecan's new labeling recommends that clinicians consider reducing the dosage of irinotecan in patients homozygous for UGT1A1*28."	( Pharmacogenetics and irinotecan therapy. Hahn, KK; Kolesar, JM; Wolff, JJ, 2006)	0.33
" According to the dosage and schedule of irinotecan, efficacy and toxicity profiles showed subtle differences."	( Three-week schedule of irinotecan plus cisplatin in patients with previously untreated extensive-stage small-cell lung cancer. Ahn, JS; Ahn, MJ; Hong, YS; Hwang, IG; Lee, HR; Lee, J; Lee, SC; Lim, HY; Park, BB; Park, K; Park, S, 2006)	0.33
" A phase I design of concerted dose escalation and dosing duration was implemented to assess the potential schedule dependency of tolerability that emerged from animal studies."	( Concerted escalation of dose and dosing duration in a phase I study of the oral camptothecin gimatecan (ST1481) in patients with advanced solid tumors. Baselga, J; Capri, G; Carminati, P; Cerny, T; Cresta, S; D'Incalci, M; Gatti, B; Gianni, L; Hess, D; Malossi, A; Marsoni, S; Rota Caremoli, E; Sessa, C; Trigo, J; Zaniboni, A; Zanna, C; Zucchetti, M, 2007)	0.57
" The initial dose of CPT-11 was 80 mg, and we thereafter made minor adjustments in the dosage depending on the occurrence of side effects."	( [Successful CPT-11 treatment in a patient with pancreatic cancer associated with multiple liver metastases and chronic renal failure]. Fujioka, T; Hirashima, Y; Kitajima, K; Kumamoto, T; Murakami, K; Sugi, S, 2007)	0.34
" Blood samples were obtained up to 55 hours after dosing and analyzed for irinotecan and its metabolites (SN-38, SN-38G), respectively, or docetaxel."	( Medicinal cannabis does not influence the clinical pharmacokinetics of irinotecan and docetaxel. de Bruijn, P; de Jong, FA; Engels, FK; Kitzen, JJ; Loos, WJ; Mathijssen, RH; Mathot, RA; Sparreboom, A; Verweij, J, 2007)	0.34
" Irinotecan was dosed initially at 30 mg/m2 per week for 7 weeks and was increased by 10 mg/m2 per week in three- to six-patient cohorts."	( Phase I study of radical thoracic radiation, weekly irinotecan, and cisplatin in locally advanced non-small cell lung carcinoma. Feigenberg, S; Huang, C; Langer, CJ; Litwin, S; Maiale, C; Millenson, M; Movsas, B; Nicoloau, N; Sherman, E; Somer, R; Treat, J, 2007)	0.34
" Other dosing regimens were not as effective."	( Velafermin improves gastrointestinal mucositis following irinotecan treatment in tumor-bearing DA rats. Alvarez, E; Bowen, JM; Burns, J; Gibson, RJ; Keefe, DM; Logan, RM; Stringer, AM; Yeoh, AS, 2007)	0.34
" Two sequential schema were used: Arm A fixed the dose of irinotecan at 100 mg/m(2) and escalated capecitabine in cohorts, and arm B fixed the dose of capecitabine at 750 mg/m(2) PO BID and escalated the dosage of irinotecan."	( A Phase I dose-finding study using an innovative sequential biweekly schedule of irinotecan followed 24 hours later by capecitabine. Allen, SL; Budman, DR; Fricano, M; Gonzales, A; Hirawat, S; Kolitz, J; Lichtman, SM; Villani, G, )	0.13
" Repetitive dosing was feasible with prolonged disease stabilization in 8 patients."	( A Phase I dose-finding study using an innovative sequential biweekly schedule of irinotecan followed 24 hours later by capecitabine. Allen, SL; Budman, DR; Fricano, M; Gonzales, A; Hirawat, S; Kolitz, J; Lichtman, SM; Villani, G, )	0.13
" The dose-response relationships for melphalan and irinotecan in individual samples showed great variability."	( Heterogeneous activity of cytotoxic drugs in patient samples of peritoneal carcinomatosis. Glimelius, B; Graf, W; Grundmark, B; Larsson, R; Mahteme, H; Nygren, P; Påhlman, L; Tholander, B; von Heideman, A, 2008)	0.35
" Therefore, UGT1A1 genotyping is not a useful prognostic indicator of severe toxicity for patients treated with this irinotecan dosage and schedule."	( UGT1A1 promoter genotype correlates with SN-38 pharmacokinetics, but not severe toxicity in patients receiving low-dose irinotecan. Billups, C; Fraga, CH; Furman, WL; Gajjar, A; Liu, T; McGregor, LM; O'Shaughnessy, MA; Owens, T; Panetta, JC; Rodriguez-Galindo, C; Stewart, CF; Throm, SL, 2007)	0.34
"Poly(ethylene oxide)-b-poly(propylene oxide)-b-(polyethylene oxide)-g-poly(acrylic acid), a graft-comb copolymer of Pluronic 127 and poly(acrylic acid) (Pluronic-PAA), was explored as an excipient for tablet dosage form of camptothecin (CPT)."	( Controlled release camptothecin tablets based on pluronic and poly(acrylic acid) copolymer. Effect of fabrication technique on drug stability, tablet structure, and release mode. Alvarez-Lorenzo, C; Barreiro-Iglesias, R; Bromberg, L; Concheiro, A; Hatton, TA, 2007)	0.85
" Results should be integrated in protocols for monitoring and assessment the dosage of drugs."	( [Role of pharmacogenetics in chemotherapy of colorectal cancers]. Beauvillain, L; Bihannic, R; Bousquet, A; Burnat, P; Ceppa, F; Cremades, S; Fontan, E, 2007)	0.34
" The SN-38 hypomicrons increased the solubility of SN-38 in water and were valuable for the development of the novel dosage form of SN-38."	( [Preparation and characterization of 7-ethyl-10-hydroxycamptothecin-loaded hypomicron of amphiphilic block copolymer]. Luan, LB; Wu, QL, 2007)	0.59
" Our data support the need for more prospective studies that evaluate the predictive value of UGT1A1 as well as UGT1A1-based dosing in patients receiving irinotecan."	( Increased frequency of uridine diphosphate glucuronosyltransferase 1A1 7/7 in patients experiencing severe irinotecan-induced toxicities. Fakih, MG; Ross, ME; Starostik, P, 2007)	0.34
"Different dosing regimens of S-CKD602, free CKD-602 and topotecan were compared for antitumor activity in female athymic nude mice bearing human A375 melanoma, ES-2 ovarian, H82 SCLC or HT-29 colon tumor xenografts."	( STEALTH liposomal CKD-602, a topoisomerase I inhibitor, improves the therapeutic index in human tumor xenograft models. Chen, JY; Conway, C; Pena, RL; Yu, NY, )	0.13
" In A375 tumors, once-weekly dosing of S-CKD602 was superior to once every 2 weeks or twice weekly schedules."	( STEALTH liposomal CKD-602, a topoisomerase I inhibitor, improves the therapeutic index in human tumor xenograft models. Chen, JY; Conway, C; Pena, RL; Yu, NY, )	0.13
" The dosing regimen recommended in clinic trial is 8 mg/m(2)."	( [10-hydroxy-camptothecin plus fluorouracil/leucovorin for the treatment of patients with advanced colorectal cancer]. Cai, RG; Chen, SS; Chu, DT; Wu, F; Zhang, HG, 2007)	0.72
" These dosing schedules resulted in significant effects on tumor vasculature, with decreased volume transfer constants, area under the curve, and permeability surface factor as well as increased gadolinium clearance after 30 days of treatment."	( Investigation of two dosing schedules of vandetanib (ZD6474), an inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling, in combination with irinotecan in a human colon cancer xenograft model. Ciardiello, F; Eckhardt, SG; Gustafson, DL; Henthorn, TK; Lockerbie, O; Long, M; Merz, A; Morrow, M; Serkova, NJ; Troiani, T, 2007)	0.34
" SLM was given orally twice daily (BID) for one week (loading) followed by continuous once daily (QD) dosing (maintenance)."	( A Phase I and pharmacokinetic study of selenomethionine in combination with a fixed dose of irinotecan in solid tumors. Badmaev, V; Brady, W; Creaven, PJ; Fakih, MG; Pendyala, L; Prey, JD; Ross, ME; Rustum, YM; Smith, PF, 2008)	0.35
" The dosage of FOLFOX 4 was reduced after three courses due to neutropenia and diarrhea."	( [A patient with recurrent rectal cancer in whom pulmonary metastasis disappeared by FOLFOX 4 therapy]. Fujisawa, M; Ishibiki, Y; Ishiyama, S; Kitabatake, T; Kojima, K; Machida, M; Nakayama, Y; Nitta, S; Ono, S; Shinjou, K; Urao, M, 2007)	0.34
" Although select patients may benefit from treatment, the overall risk:benefit ratio is unfavorable, and other dosing regimens and therapeutic options should be explored in this setting."	( Excess toxicity associated with docetaxel and irinotecan in patients with metastatic, gemcitabine-refractory pancreatic cancer: results of a phase II study. Bergsland, EK; Dito, E; Ko, AH; Schillinger, B; Tempero, MA; Venook, AP, 2008)	0.35
" In the event of progressive disease, the dosage was increased for subsequent cycles."	( [Irinotecan plus gemcitabine(IRINOGEM)in the treatment of biliary malignancies]. Hatakeyama, K; Muneoka, K; Sakata, J; Sasaki, M; Shirai, Y; Toshima, M; Wakai, T, 2008)	0.35
" Further study is needed for a selection of suitable chemotherapeutic regimens, an optimal dosage of each drug and timing of hemodialysis."	( [Carboplatin and CPT-11 chemotherapy in a hemodialysis patient with small-cell lung cancer]. Baba, M; Hayashi, N; Kakimoto, Y; Koshiishi, H; Koshiishi, Y; Minami, T; Okamura, T; Takahashi, E; Yasui, T, 2007)	0.34
" The currently approved dosing regimen for cetuximab is a 400-mg/m(2) initial dose followed by 250 mg/m(2) weekly."	( Administration of cetuximab every 2 weeks in the treatment of metastatic colorectal cancer: an effective, more convenient alternative to weekly administration? Cervantes, A; Pfeiffer, P; Tabernero, J, 2008)	0.35
" A dosage of 335 mg/m2/day of UFT was given perorally on daily schedule."	( Metronomic chemotherapy using weekly low-dosage CPT-11 and UFT as postoperative adjuvant therapy in colorectal cancer at high risk to recurrence. Akagi, Y; Fukushima, T; Ishibashi, N; Mori, S; Murakami, H; Ogata, Y; Shirouzu, K; Ushijima, M, 2007)	0.34
"Recent progress in pharmacogenetic research has made "personalized medicine" a reality, where a suitable drug at the appropriate dosage is prescribed based on individual genetic factors."	( [Irinotecan pharmacogenetics in Japanese cancer patients: roles of UGT1A1*6 and *28]. Minami, H; Sai, K; Sawada, J, 2008)	0.35
" Based on these results, male MutaMouse mice (5 per group) were dosed daily with bleomycin (50 mg/kg bw) for 5 days or with camptothecin (5 mg/kg bw) for 2 days."	( Is MutaMouse insensitive to clastogens? Bradford, A; Brockhurst, K; Lynch, AM; Mahabir, AG; Rees, RW; van Benthem, J; van Steeg, H, 2008)	0.55
" Finally, the application of a 3-weekly high-dose treatment regimen with a 20% reduced dosage compared with the low-dose weekly irinotecan regimen in patients with UGT1A1 7/7 genotype was less expensive and is more convenient for the patient."	( Cost-effectiveness of UGT1A1 genotyping in second-line, high-dose, once every 3 weeks irinotecan monotherapy treatment of colorectal cancer. Kos, M; Mrhar, A; Obradovic, M, 2008)	0.35
" Future studies should combine pharmacogenetics with clinical determinants such as performance status and co-medication as to predict irinotecan toxicity and to develop predefined dosing algorithms."	( Clinical and pharmacogenetic factors associated with irinotecan toxicity. Gelderblom, H; Guchelaar, HJ; Kweekel, D, 2008)	0.35
" The Bayesian optimal dose finding suggested a different solution, closest to that of the latter dosing which may be less toxic."	( Optimal modeling for phase I design of a two drug combination-results of a phase I study of cisplatin with 9-nitrocamptothecin. Gounder, M; Gu, Z; Kudelka, AP; Lee, SJ; Li, JM; Loyer, E; Rubin, EH; Thalasila, A; Verschraegen, CF, 2008)	0.56
" Cohorts of six patients were recruited sequentially to one of three fixed starting dose groups-2, 4, or 7 mg, with drug administered by fixed-dose rather than dosing by body surface area."	( A multi-centre dose-escalation and pharmacokinetic study of diflomotecan in patients with advanced malignancy. Cendros, JM; Evans, TR; Falk, S; Graham, JS; Samuel, LM, 2009)	0.35
" Alternative oral dosing schedules of diflomotecan have been shown to display a more predictable PK/PD and safety profile and should be selected for further evaluation in Phase II clinical trials."	( A multi-centre dose-escalation and pharmacokinetic study of diflomotecan in patients with advanced malignancy. Cendros, JM; Evans, TR; Falk, S; Graham, JS; Samuel, LM, 2009)	0.35
" Irinotecan labeling recommends testing for the UGT1A1*28 allele and reducing irinotecan dosing in patients who are positive to reduce the likelihood of dose-limiting neutropenia only, but not diarrhea."	( Irinotecan and uridine diphosphate glucuronosyltransferase 1A1 pharmacogenetics: to test or not to test, that is the question. Deeken, JF; Marshall, JL; Slack, R, 2008)	0.35
" When administered concurrently with enzyme-inducing antiepileptic drugs, the dosage must be increased to compensate for enhanced cytochrome CY3A4/5 enzyme activity."	( Experience with irinotecan for the treatment of malignant glioma. Desjardins, A; Friedman, HS; Reardon, DA; Vredenburgh, JJ, 2009)	0.35
"The aims of this trial were to assess the safety and efficacy of two different dosing schedules of irinotecan (CPT-11) in recurrent glioma patients, to assess irinotecan pharmacokinetics in patients on enzyme-inducing antiepileptic drugs (EIAEDs) and steroids, and to correlate with toxicity and response to treatment."	( Phase II trial of two different irinotecan schedules with pharmacokinetic analysis in patients with recurrent glioma: North Central Cancer Treatment Group results. Ames, MM; Buckner, JC; Felten, SJ; Galanis, E; Jaeckle, KA; Nikcevich, DA; Reid, JM; Santisteban, M; Scheithauer, BW; Wiesenfeld, M; Wu, W, 2009)	0.35
" At the MTD, mean peak concentrations of the drug in plasma ranged from 67 to 82 ng/mL for the 3 weekly doses and the mean concentration 7 days after dosing was 15 +/- 18 ng/mL."	( Phase I and pharmacokinetic study of gimatecan given orally once a week for 3 of 4 weeks in patients with advanced solid tumors. Amato, A; Clark, JW; He, X; Lynch, TJ; Pace, S; Ready, N; Ryan, DP; Safran, H; Salem, N; Supko, JG; Zhu, AX; Zvereva, N, 2009)	0.35
"The EGAPP Working Group (EWG) found no intervention trials showing that targeted dosing of irinotecan based on UGT1A1 genotyping could reduce the rates of two specific adverse drug events, severe (Grade 3-4) neutropenia or diarrhea."	( Recommendations from the EGAPP Working Group: can UGT1A1 genotyping reduce morbidity and mortality in patients with metastatic colorectal cancer treated with irinotecan? , 2009)	0.35
" The EWG found adequate evidence of a significantly higher rate of tumor response to standard irinotecan dosing among individuals with the genotype at highest risk of adverse drug events (*28/*28)."	( Recommendations from the EGAPP Working Group: can UGT1A1 genotyping reduce morbidity and mortality in patients with metastatic colorectal cancer treated with irinotecan? , 2009)	0.35
" Preliminary modeling suggests that, even if targeted dosing were to be highly effective, it is not clear that benefits (reduced adverse drug events) outweigh harms (unresponsive tumors)."	( Recommendations from the EGAPP Working Group: can UGT1A1 genotyping reduce morbidity and mortality in patients with metastatic colorectal cancer treated with irinotecan? , 2009)	0.35
" Verapamil (25mg/kg) was administered orally 2h before irinotecan oral (80 mg/kg) or intravenous (20mg/kg) dosing in female Wistar rats."	( Effect of P-glycoprotein inhibitor, verapamil, on oral bioavailability and pharmacokinetics of irinotecan in rats. Bansal, T; Jaggi, M; Khar, RK; Mishra, G; Talegaonkar, S, 2009)	0.35
" This is the first clinical evaluation of fixed drug ratio dosing designed to maintain synergistic molar ratios for enhanced therapeutic benefit."	( Safety, pharmacokinetics, and efficacy of CPX-1 liposome injection in patients with advanced solid tumors. Batist, G; Chi, KN; Chia, SK; Gelmon, KA; Janoff, AS; Louie, AC; Mayer, LD; Miller, WH; Swenson, CE, 2009)	0.35
" The purpose of this article is to review the available information on capecitabine with respect to clinical efficacy for tumors of the digestive tract, adverse-effect profile, documented drug interactions, dosage and administration, and future directions of ongoing research."	( The role of capecitabine in the management of tumors of the digestive system. Gennatas, C; Gennatas, S; Michalaki, V, 2009)	0.35
" As the drug was well tolerated, the dosage was increased to 80 mg/m(2) after 2 cycles."	( Irinotecan in cancer patients with end-stage renal failure. Boesler, B; Czock, D; Keller, F; Rasche, FM; Shipkova, M, 2009)	0.35
"We conclude that approximately two-thirds of the standard weekly irinotecan dosage regimen should be considered in patients with ESRF."	( Irinotecan in cancer patients with end-stage renal failure. Boesler, B; Czock, D; Keller, F; Rasche, FM; Shipkova, M, 2009)	0.35
" Dosing schemas were based on the maximum-tolerated dose derived in a previous phase I study."	( Phase II trial of irinotecan and carboplatin for extensive or relapsed small-cell lung cancer. Chen, G; Fehrenbacher, L; Gandara, D; Goldstein, D; Huynh, M; Lara, PN; Lau, D; Russin, M; West, H; Yavorkovsky, LL, 2009)	0.35
" Our present findings reveal the underlying mechanism by which GCs enhance the chemotherapeutic effect of CPT-11 and indicate the possibility that the dosage of CPT-11 could be reduced by the combination treatment with GCs, which may attenuate the adverse effect without decreasing anti-tumor activity."	( Role of glucocorticoid receptor in the regulation of cellular sensitivity to irinotecan hydrochloride. Akagi, T; Aramaki, H; Fujii, A; Fukagawa, T; Higuchi, S; Iba, H; Ikemura, T; Kage, Y; Koyanagi, S; Matsunaga, N; Ohdo, S; To, H; Uchida, A, 2009)	0.35
" Additionally, no dosage decrease was required, and only 4 cycles were withheld for 1 week because of neutropenia."	( Efficacy and safety of capecitabine and oxaliplatin combination as second-line treatment in advanced colorectal cancer. Hatzopoulos, A; Heras, P; Karagiannis, S; Kritikos, K; Kritikos, N; Mitsibounas, D; Xourafas, V, )	0.13
" We found that STI571 had synergistic effects with cisplatin in BT-549 and to some extent in MDA-MB-468 cells; synergized with camptothecin using an alternate dosing regimen in MDA-MB-231 cells; and STI571 synergistically sensitized MDA-MB-468 cells to paclitaxel and to high doses of 5-fluorouracil."	( STI571 sensitizes breast cancer cells to 5-fluorouracil, cisplatin and camptothecin in a cell type-specific manner. Fiore, LS; Ganguly, S; Holler, CJ; Park, ES; Plattner, R; Sims, JT, 2009)	0.79
" In the human HT-29 colon tumor xenograft mouse model, SSA significantly inhibited tumor growth at a dosage of 250 mg/kg."	( A novel sulindac derivative that does not inhibit cyclooxygenases but potently inhibits colon tumor cell growth and induces apoptosis with antitumor activity. Coward, L; Gary, BD; Gorman, G; Hobrath, JV; Keeton, AB; Li, Y; Mathew, B; Maxuitenko, YY; Piazza, GA; Reynolds, RC; Sani, B; Thaiparambil, J; Tinsley, HN; Whitt, JD, 2009)	0.35
" With genetic testing, irinotecan dosage was reduced 25% in homozygotes with the UGT1A1*28 variant allele."	( Cost effectiveness of pharmacogenetic testing for uridine diphosphate glucuronosyltransferase 1A1 before irinotecan administration for metastatic colorectal cancer. Blinder, V; Gold, HT; Hall, MJ; Schackman, BR, 2009)	0.35
" The CPT-11 dosage was 150 mg/m(2)."	( [Two cases of advanced colorectal cancer with UGT1A1*28 homozygosity treated by FOLFIRI]. Fukuoka, T; Hatano, N; Imamura, Y; Morita, Y; Usui, H; Yokoyama, S, 2009)	0.35
"Weekly dosing of combination of irinotecan and docetaxel is active against MBC."	( N0332 phase 2 trial of weekly irinotecan hydrochloride and docetaxel in refractory metastatic breast cancer: a North Central Cancer Treatment Group (NCCTG) Trial. Anderson, DM; Bernath, AM; Gamini, SS; Hillman, DW; Niedringhaus, R; Northfelt, DW; Palmieri, F; Perez, EA; Salim, M; Stella, PJ; Tan, WW, 2010)	0.36
"The HCPT-PEG-PCL-NPs increase the solubility of HCPT in water and are valuable for the development of the novel dosage form of HCPT."	( [Preparation and characterization of hydroxycamptothecin nanoparticles of amphiphilic block copolymer]. Hou, LB; Xi, N, 2009)	0.61
" Starting chemotherapy dosage (dose level: 0) was capecitabine 550 mg/m bid, day 1 to 5 every week through out x-ray therapy, irinotecan 30 mg/ m IV on days 1, 8, 22, 29 (no treatment on day 15 and day 36), and celecoxib 400 mg PO bid from day 1 till the last day of radiation."	( A phase I study of capecitabine, irinotecan, celecoxib, and radiation as neoadjuvant therapy of patients with locally advanced rectal cancer. Alqaisi, M; Bernal, P; Bush, D; Byrd, J; Garberoglio, C; Hussein, F; Malik, I, 2010)	0.36
"Recommended dosage for future trials is capecitabine 625 mg/m bid, irinotecan 35 mg/m, and celecoxib 400 mg orally bid in combination with pelvic radiation."	( A phase I study of capecitabine, irinotecan, celecoxib, and radiation as neoadjuvant therapy of patients with locally advanced rectal cancer. Alqaisi, M; Bernal, P; Bush, D; Byrd, J; Garberoglio, C; Hussein, F; Malik, I, 2010)	0.36
"A PK/PD model was built that linked the dosing regimen of a compound to the inhibition of tumor growth in mouse xenograft models."	( Preclinical pharmacokinetic/pharmacodynamic models to predict synergistic effects of co-administered anti-cancer agents. Ashwell, S; Brassil, PJ; Dai, J; Garner, CE; Gönen, M; Goteti, K; Kern, SE; Moustakas, DT; Schwartz, GK; Utley, L; Zabludoff, S, 2010)	0.36
" When Model II was applied to the antitumor activity of irinotecan and flavopiridol combination therapy, the modeling was able to reproduce the optimal dosing interval between administrations of the compounds."	( Preclinical pharmacokinetic/pharmacodynamic models to predict synergistic effects of co-administered anti-cancer agents. Ashwell, S; Brassil, PJ; Dai, J; Garner, CE; Gönen, M; Goteti, K; Kern, SE; Moustakas, DT; Schwartz, GK; Utley, L; Zabludoff, S, 2010)	0.36
"The every 2 week dosing is well tolerated with a phase II recommended dose of 45 mg/m of flavopiridol in combination with irinotecan (80 mg/m) and gemcitabine (800 mg/m)."	( A phase I study of flavopiridol in combination with gemcitabine and irinotecan in patients with metastatic cancer. Chyi Lee, F; Fekrazad, HM; Rabinowitz, I; Royce, M; Smith, HO; Verschraegen, CF, 2010)	0.36
" It is also considered necessary to adjust the dosage of the anticancer drugs and the dosing period for patients with a PS of 2 when preparing a chemotherapeutic regimen for digestive carcinoma, including stomach carcinoma."	( [Combination chemotherapy of S-1 and CPT-11 for advanced recurrent gastric cancer]. Akasaka, O; Anan, H; Ando, T; Iwase, S; Kasama, M; Koh, R; Matsueda, R; Miwa, H; Morita, S, 2009)	0.35
"Although triweekly administration of paclitaxel is approved for gastric cancer in Japan, currently, the drug is often delivered with a weekly schedule because of the equivalent efficacy and lesser toxicity of this dosing schedule as compared with the triweekly administration schedule."	( Weekly paclitaxel for heavily treated advanced or recurrent gastric cancer refractory to fluorouracil, irinotecan, and cisplatin. Boku, N; Fukutomi, A; Hironaka, S; Kojima, T; Machida, N; Onozawa, Y; Sakamoto, T; Shimoyama, R; Taku, K; Todaka, A; Tomita, H; Tsushima, T; Yamazaki, K; Yasui, H, 2009)	0.35
"Individualized drug dosing is a longstanding goal of clinical pharmacologists."	( Individualizing dosing of irinotecan. Innocenti, F; Ratain, MJ, 2010)	0.36
"Twenty-six patients were treated at nine dosage levels (1."	( A phase I study of 7-t-butyldimethylsilyl-10-hydroxycamptothecin in adult patients with refractory or metastatic solid malignancies. Arnold, SM; DeSimone, PA; Eckardt, JR; Fields, SZ; Kee, BK; Leggas, M; Moscow, JA; Rinehart, JJ; Shelton, BJ; Tsakalozou, E, 2010)	0.61
" This phase I study was performed to determine the recommended dosage (RD) of metronomic chemotherapy using oral fluoropyrimidine S-1 plus weekly irinotecan (CPT-11) in patients with previously untreated advanced or recurrent colorectal cancer."	( Dosage escalation study of S-1 and irinotecan in metronomic chemotherapy against advanced colorectal cancer. Akagi, Y; Ishibashi, N; Mori, S; Ogata, Y; Sasatomi, T; Shirouzu, K, 2009)	0.35
" The goal of this review is to summarize the relevant literature for others interested in the field of camptothecin-based therapeutics, specifically in the context of biodistribution, dosing regimens, and pharmacokinetics with the desire of providing a useful source of comparative data."	( Cancer therapies utilizing the camptothecins: a review of the in vivo literature. Simanek, EE; Venditto, VJ, 2010)	0.86
"There is no major difference of efficacy and safety between cetuximab given every 2 weeks and a weekly dosing regimen, in association with irinotecan."	( Irinotecan associated with cetuximab given every 2 weeks versus cetuximab weekly in metastatic colorectal cancer. De la Fouchardiere, C; Desseigne, F; Dussart, S; Errihani, H; Mrabti, H; Negrier, S, )	0.13
"Thirty-two patients with unresectable stage IIIA/B NSCLC received irinotecan (30 mg/m) and carboplatin dosed to a target area under the concentration curve of 2, each administered weekly for 7 weeks."	( Efficacy and toxicity of chemoradiotherapy with carboplatin and irinotecan followed by consolidation docetaxel for unresectable stage III non-small cell lung cancer. Bastos, BR; Gomez, J; Hatoum, GF; Lopes, G; Raez, LE; Santos, ES; Takita, C; Tolba, K; Walker, GR, 2010)	0.36
" As the drug is orally administered, capecitabine permits greater convenience and flexibility in dosing by eliminating the need for continuous infusion and its potential complications."	( Dosing considerations for capecitabine-irinotecan regimens in the treatment of metastatic and/or locally advanced colorectal cancer. Boehm, KA; Cartwright, T; McCollum, D, 2010)	0.36
"75) would seem to provide a good index of dosage requirement of CPT-11 in pediatric patients."	( Pharmacokinetic and pharmacodynamic investigation of irinotecan hydrochloride in pediatric patients with recurrent or progressive solid tumors. Barrett, JS; Ida, K; Ishida, Y; Kaneko, M; Kashiwase, S; Kimura, T; Kumagai, M; Makimoto, A; Mugishima, H; Nagatoshi, Y; Taga, T, 2010)	0.36
" The synergy with docetaxel depended on the treatment sequence; a schedule of MK-2206 dosed before docetaxel was not effective."	( MK-2206, an allosteric Akt inhibitor, enhances antitumor efficacy by standard chemotherapeutic agents or molecular targeted drugs in vitro and in vivo. Hatch, H; Hirai, H; Kotani, H; Majumder, PK; Miyama, K; Nakatsuru, Y; Pan, BS; Sootome, H; Taguchi, S; Tsujioka, K; Ueno, Y, 2010)	0.36
" Previous studies have reported the toxic effects of the test article following repeated IV dosing of CKD-602, a novel camptothecin-derivative anti-tumor agent that was developed by Chong Kun Dang Pharmaceutical Corporation in Seoul, Korea."	( Toxicity study of a new camptothecin anti-cancer agent CKD-602 in dogs: 4-week continuous intravenous dose by infusion pump and 4-week repeated intravenous dose. Han, EH; Han, SC; Hwang, IC; Kim, CY; Kim, DG; Kim, YB, 2010)	0.88
" For Docetaxel and 5-FU, a linear correlation between this sensitizing effect and the ascorbate dosage is observed."	( Ascorbate exerts anti-proliferative effects through cell cycle inhibition and sensitizes tumor cells towards cytostatic drugs. Aigner, A; Czubayko, F; Frömberg, A; Gutsch, D; Schulze, D; Vollbracht, C; Weiss, G, 2011)	0.37
" The review aims to provide an evidence-based update of clinical trials investigating the clinical efficacy, adverse-event profile, dosage and administration of this drug, alone or in combination with conventional chemotherapeutics and/or new target-oriented drugs, in the management of colorectal cancer patients."	( Update on capecitabine alone and in combination regimens in colorectal cancer patients. Azzariti, A; Cinieri, S; Colucci, G; De Vita, F; Lorusso, V; Maiello, E; Millaku, A; Numico, G; Petriella, D; Pisconti, S; Russo, A; Santini, D; Silvestris, N; Tommasi, S, 2010)	0.36
"The 23 patients for a single-dose pharmacokinetic experiment were divided into 3 dosing cohorts."	( A phase I pharmacokinetics study of 9-nitrocamptothecin in patients with advanced solid tumors. Chen, P; Huang, C; Li, K; Liu, M; Wang, L; Xue, J; Yan, Z; Zhu, Z, 2011)	0.63
" These observations have potential implications in the optimal dosing of liposomal agents."	( Population pharmacokinetics of pegylated liposomal CKD-602 (S-CKD602) in patients with advanced malignancies. Bang, YJ; Belani, CP; Edwards, RP; Friedland, DM; Maruca, LJ; Ramalingam, S; Ramanathan, RK; Stoller, RG; Strychor, S; Wu, H; Zamboni, BA; Zamboni, WC, 2012)	0.38
" 3a and 3b demonstrated significant brain penetration when dosed orally in mice."	( 14-Aminocamptothecins: their synthesis, preclinical activity, and potential use for cancer treatment. Ahluwalia, D; Bhupathi, D; Cai, X; Duan, JX; Hart, CP; Huang, H; Jiao, H; Jung, B; Jung, D; Liu, Q; Matteucci, J; Matteucci, M; Meng, F; Sun, JD, 2011)	0.8
" Despite this, 150 mg/m(2) CPT is widely prescribed and is the maximum dosage covered by Japanese health insurance."	( Retrospective analysis of the international standard-dose FOLFIRI (plus bevacizumab) regimen in Japanese patients with unresectable advanced or recurrent colorectal carcinoma. Akutsu, N; Fujii, H; Hamamoto, Y; Miyamoto, J; Nagase, M; Nishi, T; Warita, E; Yamanaka, Y, 2011)	0.37
" Cetuximab was given at the approved dosage to all patients."	( Retrospective analysis of cetuximab monotherapy for patients with irinotecan-intolerant metastatic colorectal cancer. Inaba, Y; Kato, M; Kondo, C; Mizota, A; Muro, K; Nomura, M; Sato, Y; Shitara, K; Takahari, D; Ura, T; Yamaura, H; Yokota, T, 2011)	0.37
"5 and 50 mg/day) and continuous daily dosing (CDD; 37."	( A phase I study of sunitinib in combination with FOLFIRI in patients with untreated metastatic colorectal cancer. Aranda, E; Carrato, A; Chau, I; Countouriotis, AM; Cunningham, D; Guillen-Ponce, C; Iveson, TJ; Ramos, FJ; Ruiz-Garcia, A; Saunders, MP; Starling, N; Tabernero, J; Tursi, JM; Vázquez-Mazón, F; Wei, G, 2012)	0.38
"Administration of an oral cephalosporin allowed advancement of the dosage of oral irinotecan."	( Dose escalation of intravenous irinotecan using oral cefpodoxime: a phase I study in pediatric patients with refractory solid tumors. Crews, KR; Furman, WL; Houghton, PJ; McCarville, MB; McGregor, LM; Navid, F; Rodriguez-Galindo, C; Santana, VM; Stewart, CF; Tagen, M; Wozniak, A; Wu, J, 2012)	0.38
" Cohorts of 3-6 pediatric patients with refractory solid tumors were enrolled at 4 dosage levels, starting at the single-agent irinotecan MTD of 20 mg/m(2) /dose."	( Dose escalation of intravenous irinotecan using oral cefpodoxime: a phase I study in pediatric patients with refractory solid tumors. Crews, KR; Furman, WL; Houghton, PJ; McCarville, MB; McGregor, LM; Navid, F; Rodriguez-Galindo, C; Santana, VM; Stewart, CF; Tagen, M; Wozniak, A; Wu, J, 2012)	0.38
"Patients with metastatic colorectal cancer who had progressed on therapy with 5-FU, oxaliplatin and irinotecan in the first and second line setting and on the combination of irinotecan and cetuximab in third line setting independent of their KRAS mutation status, were treated with irinotecan and cetuximab combined with bevacizumab in a dosage of 5 mg/kg."	( Bevacizumab in combination with cetuximab and irinotecan after failure of cetuximab and irinotecan in patients with metastatic colorectal cancer. Bjerregaard, JK; Fromm, AL; Hoegdall, E; Jensen, BV; Jørgensen, TL; Larsen, FO; Nielsen, D; Pfeiffer, P; Qvortrup, C; Skougaard, K; Vistisen, K, 2011)	0.37
" Considering the rapid formation of SN-38, the proportional increase in exposure levels, and its longer elimination half-life, less frequent dosing of SN2310 emulsion may be considered for the treatment of patients with advanced solid malignancies."	( Pharmacokinetics of SN2310, an injectable emulsion that incorporates a new derivative of SN-38 in patients with advanced solid tumors. Anderson, K; Burris, HA; Jones, S; Marier, JF; Pheng, L; Porubek, D; Trinh, MM; Warner, S, 2011)	0.37
" The circadian disruptive effects of irinotecan, a topoisomerase I inhibitor, was investigated according to dosing time and sex."	( Sex and dosing-time dependencies in irinotecan-induced circadian disruption. Ahowesso, C; Beau, J; Claustrat, B; Delaunay, F; Dulong, S; Filipski, E; Hossard, V; Lévi, F; Li, XM; Peteri-Brunbäck, B; Zampera, S, 2011)	0.37
" Further studies with this regimen using the dosing schedules evaluated in this study are not warranted."	( Phase I study of sunitinib and irinotecan for patients with recurrent malignant glioma. Coan, A; Desjardins, A; Friedman, HS; Gururangan, S; Herndon, JE; Peters, KB; Reardon, DA; Rich, JN; Sathornsumetee, S; Vredenburgh, JJ, 2011)	0.37
" Using colorectal xenograft models, we examined the therapeutic benefit of Cathepsin S inhibition using Fsn0503 in combination with a metronomic dosing regimen of CPT-11."	( Inhibition of Cathepsin S by Fsn0503 enhances the efficacy of chemotherapy in colorectal carcinomas. Burden, RE; Gazdoiu, M; Gormley, JA; Jaquin, TJ; Johnston, JA; Kuehn, D; Kwok, HF; McClurg, A; Olwill, SA; Scott, CJ; Ward, C, 2012)	0.38
" Irinotecan dosing started at 50 mg m(-2) and was escalated in patients by 25 mg m(-2) increments up to a maximum dose of 150 mg m(-2)."	( Phase I study of irinotecan and gefitinib in patients with gefitinib treatment failure for non-small cell lung cancer. Horai, T; Horiike, A; Kasahara, K; Kudo, K; Miyauchi, E; Nishio, M; Ohyanagi, F, 2011)	0.37
" A single injection or 2 injections of IHL-305 on several dosing schedules also resulted in a significant antitumor effect compared to that of vehicle control in a dose-dependent manner and showed comparable antitumor activity at about one-fifth the dose of the maximum tolerated dose of CPT-11."	( Antitumor activity of IHL-305, a novel pegylated liposome containing irinotecan, in human xenograft models. Furuta, T; Hashimoto, S; Kodaira, H; Kurita, A; Matsuzaki, T; Nohara, G; Sawada, S; Takagi, A; Ueno, S, 2012)	0.38
"Camptothecin analogues are anticancer drugs effective when dosed in protracted schedules."	( Pharmacokinetic modeling to assess factors affecting the oral bioavailability of the lactone and carboxylate forms of the lipophilic camptothecin analogue AR-67 in rats. Adane, ED; Anderson, BD; Leggas, M; Liu, Z; Xiang, TX, 2012)	2.03
" Liposomal drug delivery systems have the ability to provide a dual mechanism of activity where tumor accumulation can deliver high local concentrations of the drug at the site of action with concomitant slow release of the drug from carriers in the blood compartment that results in antivascular effects, similar to that achieved when dosing frequently at low levels."	( Lipid-based nanoformulation of irinotecan: dual mechanism of action allows for combination chemo/angiogenic therapy. Anantha, M; Bally, MB; Sutherland, B; Verreault, M; Waterhouse, DN; Yapp, D, 2011)	0.37
" Angiogenesis was induced in normal adult rat mesentery by intraperitoneal injection of a low dosage of VEGF-A."	( Low-dosage metronomic chemotherapy and angiogenesis: topoisomerase inhibitors irinotecan and mitoxantrone stimulate VEGF-A-mediated angiogenesis. Albertsson, P; Lennernäs, B; Norrby, K, 2012)	0.38
" We show that real-time flow cytometric quantification of compound-uptake is reliably measured and that analyzing their respective uptake kinetic provides additional valuable information which can be used for improving drug dosage and delivery."	( Utilizing inherent fluorescence of therapeutics to analyze real-time uptake and multi-parametric effector kinetics. Efferth, T; Eichhorn, T; Korn, B; Paulsen, M; Wiench, B, 2012)	0.38
" The antitumor activity, different dosing sequences, and dosing regimens of TH-302 in combination with commonly used conventional chemotherapeutics were investigated in human tumor xenograft models."	( TH-302, a hypoxia-activated prodrug with broad in vivo preclinical combination therapy efficacy: optimization of dosing regimens and schedules. Ahluwalia, D; Ammons, WS; Baker, AF; Cranmer, LD; Curd, JG; Duan, JX; Ferraro, D; Hart, CP; Liu, Q; Matteucci, MD; Sun, JD; Wang, J; Wang, Y, 2012)	0.38
" Simultaneous administration of TH-302 and chemotherapeutics increased toxicity versus schedules with dosing separations."	( TH-302, a hypoxia-activated prodrug with broad in vivo preclinical combination therapy efficacy: optimization of dosing regimens and schedules. Ahluwalia, D; Ammons, WS; Baker, AF; Cranmer, LD; Curd, JG; Duan, JX; Ferraro, D; Hart, CP; Liu, Q; Matteucci, MD; Sun, JD; Wang, J; Wang, Y, 2012)	0.38
" After recovery from the adverse event, another 4 courses at a 20% lower dosage for safety were administered."	( [A case of S-1-resistant resected advanced gastric cancer with para-aortic lymph node recurrence responding to bi-weekly CPT-11 and CDDP]. Ikeda, T; Minamoto, K; Yuasa, I, 2012)	0.38
" We conducted a phase I study to determine the AUC-calculated optimal dosage of NDP used in combination chemotherapy with irinotecan (CPT-11) for gynecologic malignancies."	( Area under the curve calculation of nedaplatin dose used in combination chemotherapy with irinotecan in a phase I study of gynecologic malignancies. Fujiwara, H; Harada, T; Itamochi, H; Kigawa, J; Machida, S; Oishi, T; Sato, S; Shimada, M; Suzuki, M; Takei, Y, 2012)	0.38
"The recommended dosage of NDP calculated by AUC with Ishibashi's formula was set to AUC 10 in combination chemotherapy with CPT-11."	( Area under the curve calculation of nedaplatin dose used in combination chemotherapy with irinotecan in a phase I study of gynecologic malignancies. Fujiwara, H; Harada, T; Itamochi, H; Kigawa, J; Machida, S; Oishi, T; Sato, S; Shimada, M; Suzuki, M; Takei, Y, 2012)	0.38
" In due course, the strategy embodied in conjugate 1 could allow for more precise monitoring of dosage levels, as well as an improved understanding of cellular uptake and release mechanisms."	( Direct fluorescence monitoring of the delivery and cellular uptake of a cancer-targeted RGD peptide-appended naphthalimide theragnostic prodrug. Bhuniya, S; Han, JH; Kang, C; Kim, JS; Kim, JY; Lee, MH; Sessler, JL, 2012)	0.38
"The objective of the current investigation was to study the degradation behavior of irinotecan hydrochloride under different International Conference on Harmonization (ICH) recommended stress conditions using ultra-performance liquid chromatography and liquid chromatography-mass spectrometry and to establish a validated stability-indicating reverse-phase ultra-performance liquid chromatographic method for the quantitative determination of irinotecan hydrochloride and its seven impurities and degradation products in pharmaceutical dosage forms."	( UPLC and LC-MS studies on degradation behavior of irinotecan hydrochloride and development of a validated stability-indicating ultra-performance liquid chromatographic method for determination of irinotecan hydrochloride and its impurities in pharmaceutic Kumar, N; Reddy, SP; Sangeetha, D, 2012)	0.38
"Vandetanib (an orally bioavailable VEGFR-2 and EGFR tyrosine kinases inhibitor) was combined at 100 mg, 200 mg, or 300 mg daily with standard dosed cetuximab and irinotecan (3+3 dose-escalation design)."	( Phase I study of cetuximab, irinotecan, and vandetanib (ZD6474) as therapy for patients with previously treated metastastic colorectal cancer. Abrams, TA; Ancukiewicz, M; Blaszkowsky, L; Chan, JA; Duda, DG; Elliott, M; Enzinger, PC; Goldstein, M; Jain, RK; Kulke, MH; Meyerhardt, JA; Regan, E; Schrag, D; Wolpin, BM; Zhu, AX, 2012)	0.38
"The efficacy and tolerability of bevacizumab every 2 or 4 weeks using the same dosage in combination with biweekly FOLFIRI were retrospectively evaluated in metastatic colorectal cancer (mCRC) patients in the first-line and second-line therapy."	( Bevacizumab every 4 weeks is as effective as every 2 weeks in combination with biweekly FOLFIRI in metastatic colorectal cancer. Alkis, N; Benekli, M; Berk, V; Buyukberber, S; Ciltas, A; Coskun, U; Dane, F; Dikilitas, M; Dogu, GG; Durnali, AG; Kaplan, MA; Karaca, H; Ozkan, M; Sevinc, A; Yetisyigit, T; Yildiz, R, 2012)	0.38
" However, our study clearly points out the need for determination of optimum biological dosing interval of bevacizumab in well-designed, prospective, randomized trials."	( Bevacizumab every 4 weeks is as effective as every 2 weeks in combination with biweekly FOLFIRI in metastatic colorectal cancer. Alkis, N; Benekli, M; Berk, V; Buyukberber, S; Ciltas, A; Coskun, U; Dane, F; Dikilitas, M; Dogu, GG; Durnali, AG; Kaplan, MA; Karaca, H; Ozkan, M; Sevinc, A; Yetisyigit, T; Yildiz, R, 2012)	0.38
" Dose escalation (n = 44) was associated with an increase in skin reactions ≥ grade 2 compared with standard (n = 45) dosing (59% v 38%, respectively)."	( Intrapatient cetuximab dose escalation in metastatic colorectal cancer according to the grade of early skin reactions: the randomized EVEREST study. Cats, A; Ciardiello, F; Gallerani, E; Gelderblom, H; Glimelius, B; Hendlisz, A; Humblet, Y; Moehler, M; Peeters, M; Sagaert, X; Schlichting, M; Tejpar, S; Van Cutsem, E; Vanbeckevoort, D; Vermorken, JB; Viret, F; Vlassak, S, 2012)	0.38
" In this study, we developed a novel microbubble carrying 10-HCPT which only needs a particularly low single dose of injection (4-6 mg) for tumor therapy in clinical application, therefore, the required high dosing of drug loaded MBs for ultrasound mediated drug delivery is not necessary."	( Ultrasound triggered drug release from 10-hydroxycamptothecin-loaded phospholipid microbubbles for targeted tumor therapy in mice. Li, P; Lin, Y; Ran, H; Ren, J; Tan, J; Wang, Z; Zhang, Q; Zheng, Y, 2012)	0.63
"IHL-305, a novel preparation of irinotecan encapsulated in liposomes, can be safely given to patients in a repeated fashion on a 4- or 2-week dosing schedule."	( Phase I and pharmacokinetic study of IHL-305 (PEGylated liposomal irinotecan) in patients with advanced solid tumors. Bendell, JC; Burris, HA; Chan, E; Ikeda, S; Infante, JR; Jones, SF; Keedy, VL; Kodaira, H; Lee, W; Rothenberg, ML; Wu, H; Zamboni, WC, 2012)	0.38
" It was designed to maximize cytoreduction via high dosing of synergistically interacting agents, while minimizing morbidity in patients with resistant neuroblastoma (NB) and ineligible for clinical trials due to myelosuppression from previous therapy."	( 5-day/5-drug myeloablative outpatient regimen for resistant neuroblastoma. Basu, EM; Cheung, NK; Kramer, K; Kushner, BH; Modak, S; Roberts, SS, 2013)	0.39
"The results in this study suggest that FOLFIRI, a common regimen combining irinotecan and 5-FU, should switch the dosing sequence, namely from 5-FU to irinotecan, to enhance hydrolytic activation of irinotecan."	( Regulation of carboxylesterase-2 expression by p53 family proteins and enhanced anti-cancer activities among 5-fluorouracil, irinotecan and doxazolidine prodrug. Charpentier, M; Guo, L; Lu, W; Xiao, D; Yan, B; Yang, D, 2013)	0.39
"Patients with advanced solid malignancies were enrolled to an open-label, single-arm, dose-escalation study, in which CRLX101 was administered intravenously over 60 min among two dosing schedules, initially weekly at 6, 12, and 18 mg/m(2) and later bi-weekly at 12, 15, and 18 mg/m(2)."	( First-in-human phase 1/2a trial of CRLX101, a cyclodextrin-containing polymer-camptothecin nanopharmaceutical in patients with advanced solid tumor malignancies. Bassett, D; Chao, J; Choi, CHJ; Chow, W; Chung, V; Davis, ME; Forman, SJ; Garmey, E; Hwang, J; Kalinoski, DL; Koczywas, M; Longmate, J; Melton, RJ; Morgan, R; Neidhart, JA; Neidhart, JD; Oliver, J; Peterkin, JJ; Ramanathan, RK; Ryan, JL; Schluep, T; Synold, TW; Twardowski, P; Weiss, GJ; Yen, Y, 2013)	0.62
" The dosing schedule appears to affect the toxicity profile of the drug."	( A systematic review on topoisomerase 1 inhibition in the treatment of metastatic breast cancer. Balslev, E; Brünner, N; Kümler, I; Nielsen, DL; Stenvang, J, 2013)	0.39
" Pharmacokinetically-directed dosing protocols of everolimus and irinotecan were established and used to assess the in vivo antitumor effects of the agents."	( Utilization of quantitative in vivo pharmacology approaches to assess combination effects of everolimus and irinotecan in mouse xenograft models of colorectal cancer. Bradshaw-Pierce, EL; Eckhardt, SG; Gustafson, DL; Kulikowski, G; Merz, AL; Pitts, TM; Selby, H; Serkova, NJ; Weekes, CD, 2013)	0.39
" Combination effects of everolimus and irinotecan were determined in CRC xenograft models using clinically-relevant dosing protocols."	( Utilization of quantitative in vivo pharmacology approaches to assess combination effects of everolimus and irinotecan in mouse xenograft models of colorectal cancer. Bradshaw-Pierce, EL; Eckhardt, SG; Gustafson, DL; Kulikowski, G; Merz, AL; Pitts, TM; Selby, H; Serkova, NJ; Weekes, CD, 2013)	0.39
" The optimum dosing combination of these two agents has yet to be determined however, and in many patients it is likely that greater overall survival will be achieved by using them in successive lines rather than in combination."	( New oxaliplatin-based combinations in the treatment of colorectal cancer. Cassidy, J; Hochster, H, 2003)	0.32
"Irinotecan dosing based on UGT1A1*28 and *6 is feasible, and higher doses of irinotecan can be safely administered in patients with 0 or 1 DA, compared to those with 2 DA."	( A UGT1A1*28 and *6 genotype-directed phase I dose-escalation trial of irinotecan with fixed-dose capecitabine in Korean patients with metastatic colorectal cancer. Bae, KS; Chang, HM; Hong, YS; Kang, YK; Kim, HS; Kim, KP; Kim, TW; Lee, JL; Lee, JS; Shin, JG; Sym, SJ, 2013)	0.39
" It is predicted that prophylaxis of CPT-11 induced diarrhea will reduce sub-therapeutic dosing as well as hospitalizations and will eventually lead to dose escalations resulting in better response rates."	( Therapeutic targeting of CPT-11 induced diarrhea: a case for prophylaxis. Goel, S; Mani, S; Swami, U, 2013)	0.39
" The goal of the contemporary research is to determine the predictive factors that will enable the individual adjustment of the individual drug dosage while minimising the adverse effects and maintaining the treatment benefit."	( Predictors of irinotecan toxicity and efficacy in treatment of metastatic colorectal cancer. Filip, S; Grim, J; Paulík, A, 2012)	0.38
"In sequential phase II studies assessing two dosing schedules, patients with metastatic colorectal cancers refractory to bevacizumab-, fluoropyrimidine-, oxaliplatin-, and irinotecan-based regimens received everolimus 70 mg/wk (n = 99) or 10 mg/d (n = 100)."	( Phase II study of everolimus in patients with metastatic colorectal adenocarcinoma previously treated with bevacizumab-, fluoropyrimidine-, oxaliplatin-, and irinotecan-based regimens. Arrowsmith, ER; Bajetta, E; Del Prete, SA; Fuchs, CS; Hwang, J; Jin, J; Malek, K; Ng, K; Ryan, DP; Sedova, M; Sharma, S; Tabernero, J, 2013)	0.39
"Traditional post-surgical chemotherapy for pancreatic cancer is notorious for its devastating side effects due to the high dosage required."	( Drug-eluting scaffold to deliver chemotherapeutic medication for management of pancreatic cancer after surgery. Chen, H; Deng, X; Jin, J; Li, H; Peng, C; Shen, B; Zhan, Q; Zhang, X, 2013)	0.39
" However, CPT-11 dosage can be adjusted according to measured SN-38 pharmacokinetics."	( Analysis of UGT1A1*28 genotype and SN-38 pharmacokinetics for irinotecan-based chemotherapy in patients with advanced colorectal cancer: results from a multicenter, retrospective study in Shanghai. Cai, X; Cao, W; Ding, H; Liu, T; Wang, L; Wang, M; Xu, Q; Zhao, Z; Zhong, M; Zhou, X, 2013)	0.39
" For the (TA)6/(TA)6 genotype, CPT-11 dosage can be increased gradually to improve efficacy for patients with SN-38 peak concentration ≤43."	( Analysis of UGT1A1*28 genotype and SN-38 pharmacokinetics for irinotecan-based chemotherapy in patients with advanced colorectal cancer: results from a multicenter, retrospective study in Shanghai. Cai, X; Cao, W; Ding, H; Liu, T; Wang, L; Wang, M; Xu, Q; Zhao, Z; Zhong, M; Zhou, X, 2013)	0.39
" Histologic observations of the epithelial layer of small intestinal segments of the gastrointestinal tract (GIT) at 4 h post dosing supported no evidence of toxicity at the evaluated doses of PAMAM dendrimers."	( Poly(amido amine) dendrimers as absorption enhancers for oral delivery of camptothecin. Bartlett, K; Ghandehari, H; Hubbard, D; McGill, LD; Ray, A; Sadekar, S; Thiagarajan, G, 2013)	0.62
" Urinary excretion of polymer-conjugated CPT occurs primarily within the initial 24 h after dosing in animals and humans."	( Correlating preclinical animal studies and human clinical trials of a multifunctional, polymeric nanoparticle. Case, RI; Chao, J; Cole, RO; Davis, ME; Eliasof, S; Han, H; Hwang, J; Lazarus, D; Lin, J; Peters, CG; Schluep, T; Wiley, DT; Yen, Y; Zuckerman, JE, 2013)	0.39
" Sensitive, rapid, and fully validated electrochemical and RP-LC methods for the determination of IRT in its dosage form were presented in details."	( Analytical application of polymethylene blue-multiwalled carbon nanotubes modified glassy carbon electrode on anticancer drug irinotecan and determination of its ionization constant value. Akmese, B; Can, A; Dogan-Topal, B; Karadas, N; Ozkan, SA; Sanli, S, 2013)	0.39
" We aimed to assess the efficacy and safety of two etirinotecan pegol dosing schedules in patients with previously treated metastatic breast cancer to determine an optimum dosing schedule for phase 3 trials."	( Two schedules of etirinotecan pegol (NKTR-102) in patients with previously treated metastatic breast cancer: a randomised phase 2 study. Awada, A; Barrett-Lee, PJ; Chan, S; Chia, YL; Cocquyt, V; Coleman, RE; Garcia, AA; Hamm, JT; Hannah, AL; Hoch, U; Huizing, MT; Jerusalem, GH; Mehdi, A; O'Reilly, SM; Perez, EA; Sideras, K; Young, DE; Zhao, C, 2013)	0.39
"UGT1A1 genotype affects the dose and pharmacokinetics of the CAPIRINOX regimen and UGT1A1 genotype-guided dosing of CAPIRINOX is ongoing in a phase II study of small bowel cancer (NCT00433550)."	( UGT1A1 genotype-guided phase I study of irinotecan, oxaliplatin, and capecitabine. Ames, MM; Erlichman, C; Goetz, MP; Goldberg, RM; Grothey, AA; Kuffel, MA; Mandrekar, SJ; McGovern, RM; McKean, HA; McWilliams, R; Reid, JM; Safgren, SL; Tan, AD, 2013)	0.39
" With current dosing regimens, axitinib plus FOLFOX or FOLFIRI seems to be less well tolerated than bevacizumab-based regimens."	( Axitinib or bevacizumab plus FOLFIRI or modified FOLFOX-6 after failure of first-line therapy for metastatic colorectal cancer: a randomized phase II study. Barone, C; Bendell, JC; Bloom, J; Kim, JG; Kim, S; Pastorelli, D; Pericay, C; Ricart, AD; Rosbrook, B; Sobrero, AF; Swieboda-Sadlej, A; Tarazi, J; Tournigand, C; Wainberg, ZA, 2013)	0.39
" However, there is a paucity of data from sufficiently powered pharmacokinetic and pharmacodynamic studies to support dosage recommendations in such patients."	( Optimization of cancer chemotherapy on the basis of pharmacokinetics and pharmacodynamics: from patients enrolled in clinical trials to those in the 'real world'. Fujita, K; Sasaki, Y, 2014)	0.4
" Dosing at ZT15 rather than ZT3 reduced mean leucopenia (9% vs 53%; p<0."	( Optimization of irinotecan chronotherapy with P-glycoprotein inhibition. Berland, E; Filipski, E; Guettier, C; Lévi, F; Okyar, A; Ozturk, N; van der Horst, GT, 2014)	0.4
"We evaluated week-on/week-off axitinib dosing plus chemotherapy in patients with gastrointestinal tumours, including tumour thymidine uptake by fluorine-18 3'-deoxy-3'-fluorothymidine positron emission tomography ((18)FLT-PET)."	( Intermittent dosing of axitinib combined with chemotherapy is supported by (18)FLT-PET in gastrointestinal tumours. Bendell, JC; Burris, HA; Hoh, CK; Infante, JR; Kim, S; Reid, TR; Rosbrook, B; Tarazi, J, 2014)	0.4
") axitinib 7 mg (n=3) or 10 mg (n=18) for 7 days followed by a 7-day dosing interruption; serial (18)FLT-PET scans were performed before day 1 and on days 7, 10, and 14."	( Intermittent dosing of axitinib combined with chemotherapy is supported by (18)FLT-PET in gastrointestinal tumours. Bendell, JC; Burris, HA; Hoh, CK; Infante, JR; Kim, S; Reid, TR; Rosbrook, B; Tarazi, J, 2014)	0.4
" To uncover the sources of heterogeneity, subgroup meta-analysis was conducted according to the dosage of IRI."	( UGT1A1*6 polymorphisms are correlated with irinotecan-induced toxicity: a system review and meta-analysis in Asians. Cheng, L; Dong, XL; Hu, J; Li, M; Liu, BR; Qian, XP; Ren, W; Sun, ZP; Xie, L; Xu, GX, 2014)	0.4
" The biological study will play a positive role in guiding and monitoring the aspects of dosage selection and judgment of therapeutic efficacy."	( Clinical therapeutic effect and biological monitoring of p53 gene in advanced hepatocellular carcinoma. Chen, J; Chen, S; Xi, W; Xu, W; Yin, G, 2014)	0.4
"3%); alteration and complete recovery (31%) or sustained deterioration (45%), possibly due to inadequate chronotherapy dosing and/or timing."	( The circadian rest-activity rhythm, a potential safety pharmacology endpoint of cancer chemotherapy. Beau, J; Innominato, PF; Iurisci, I; Karaboue, A; Lévi, F; Madrid, JA; Moreau, T; Ortiz-Tudela, E; Rol, MA, 2014)	0.4
" The ECM algorithm for incomplete data is applied to estimating the dose-response relationship in the proposed model."	( Modeling sustained treatment effects in tumor xenograft experiments. Deng, D; Fang, HB; Tan, M; Zhang, T, 2014)	0.4
" However, the clinical utility of routine UGT1A1*28 genotyping to pre-emptively adjust irinotecan dosage is dependent upon whether UGT1A1*28 also affects patient survival following irinotecan therapy."	( The effect of the UGT1A1*28 allele on survival after irinotecan-based chemotherapy: a collaborative meta-analysis. Boige, V; Dias, MM; Glimelius, B; Karapetis, CS; Kweekel, DM; Lara, PN; Laurent-Puig, P; Martinez-Balibrea, E; McKinnon, RA; Páez, D; Pignon, JP; Punt, CJ; Redman, MW; Sorich, MJ; Toffoli, G; Wadelius, M, 2014)	0.4
"After determining the maximum tolerated dose using neutropenia as a toxicity endpoint, xenografts received AR-67 under varying dosing schedules and were monitored for survival."	( Protracted dosing of the lipophilic camptothecin analogue AR-67 in non-small cell lung cancer xenografts and humans. Adane, ED; Arnold, SM; Leggas, M; Liang, Y; Tsakalozou, E, 2014)	0.68
"Low-dose protracted dosing schedules increased animal survival compared to less frequent, but higher-dose courses and the expression of Top1 and γH2AX were schedule dependent."	( Protracted dosing of the lipophilic camptothecin analogue AR-67 in non-small cell lung cancer xenografts and humans. Adane, ED; Arnold, SM; Leggas, M; Liang, Y; Tsakalozou, E, 2014)	0.68
"We demonstrated that low-dose protracted dosing schedules of AR-67 are therapeutically effective and Top1 reflects the biological activity of AR-67 in xenografts."	( Protracted dosing of the lipophilic camptothecin analogue AR-67 in non-small cell lung cancer xenografts and humans. Adane, ED; Arnold, SM; Leggas, M; Liang, Y; Tsakalozou, E, 2014)	0.68
"This study attempted to determine the therapeutic dosage of irinotecan and S-1 (IRIS) as a second-line treatment for colorectal cancer (CRC)."	( Phase I/II trial of irinotecan and S-1 combination chemotherapy as a second-line treatment for advanced colorectal cancer. Akazawa, K; Funakoshi, K; Hasegawa, J; Hatakeyama, K; Maruyama, S; Okada, T; Takii, Y; Tani, T; Yamazaki, T, 2013)	0.39
" The irinotecan dose was then escalated to determine the maximum-tolerated dose and the recommended dose at a fixed dosage of S-1 (80 or 65 mg·m(-2)·day(-1))."	( Phase I/II trial of irinotecan and S-1 combination chemotherapy as a second-line treatment for advanced colorectal cancer. Akazawa, K; Funakoshi, K; Hasegawa, J; Hatakeyama, K; Maruyama, S; Okada, T; Takii, Y; Tani, T; Yamazaki, T, 2013)	0.39
"The UGT1A1*28 genotype can be used to individualize dosing of irinotecan."	( Dose-finding and pharmacokinetic study to optimize the dosing of irinotecan according to the UGT1A1 genotype of patients with cancer. Das, S; House, LK; Innocenti, F; Janisch, L; Karrison, T; Maitland, ML; Marsh, R; Ramírez, J; Ratain, MJ; Salgia, R; Schilsky, RL; Turcich, M; Undevia, S; Wu, K, 2014)	0.4
"This review aims to provide an evidence-based update of clinical trials that have investigated the clinical efficacy, adverse-event profile, dosage and administration of S-1, given alone or in combination with conventional chemotherapeutics and new target-oriented drugs, in the management of colorectal cancer (CRC)."	( Efficacy of S-1 in colorectal cancer. Baba, H; Miyamoto, Y; Sakamoto, Y; Yoshida, N, 2014)	0.4
" But the dosing schedules are essential to achieve a balance between vascular collapse and intratumoral uptake of chemotherapeutic agents."	( Antimetastasis and antitumor efficacy promoted by sequential release of vascular disrupting and chemotherapeutic agents from electrospun fibers. Chen, M; Li, X; Luo, X; Wei, J; Zhang, H; Zhang, Y, 2014)	0.4
" Twenty-five patients received treatment in three dosing cohorts and were evaluated for safety and tolerability of the combination and pharmacokinetics of individual drugs."	( A phase I open-label study of the safety, tolerability, and pharmacokinetics of pazopanib in combination with irinotecan and cetuximab for relapsed or refractory metastatic colorectal cancer. Bennouna, J; Botbyl, J; de Labareyre, C; Delord, JP; Deslandres, M; Ruiz-Soto, R; Senellart, H; Suttle, AB; Wixon, C, 2015)	0.42
" In a mouse xenograft model of human colon carcinoma, nal-IRI dosing could achieve higher intratumoral levels of the prodrug irinotecan and its active metabolite SN-38 compared with free irinotecan."	( Preclinical activity of nanoliposomal irinotecan is governed by tumor deposition and intratumor prodrug conversion. Cain, J; Drummond, DC; Fitzgerald, JB; Kalra, AV; Kim, J; Klinz, SG; Nielsen, UB; Paz, N, 2014)	0.4
" The present study investigated the protective efficacy of α-tocopherol on the peroxidative damage and abnormal antioxidant levels in the myocardial tissue of camptothecin (CPT), administered at the dosage of 6 mg/kg/day in male Wistar rats."	( α-Tocopherol mediated amelioration of camptothecin-induced free radical damage to avert cardiotoxicities. Bhori, M; Marar, T; Singh, K, 2015)	0.88
"Seven patients with metastases confined to the liver were included and stratified into two groups, depending of dosage of systemic chemotherapy."	( Fluorouracil, leucovorin and irinotecan combined with intra-arterial hepatic infusion of drug-eluting beads preloaded with irinotecan in unresectable colorectal liver metastases: side effects and results of a concomitant treatment schedule. Clinical inves Badzek, S; Golem, H; Gorsic, I; Kekez, D; Librenjak, N; Perkov, D; Plestina, S; Prejac, J; Smiljanic, R, )	0.13
" The advantage of fractionated dosing was demonstrated, with potential implications for the clinical dosing schedule."	( Improving the therapeutic index in cancer therapy by using antibody-drug conjugates designed with a moderately cytotoxic drug. Cardillo, TM; Goldenberg, DM; Govindan, SV; McBride, WJ; Rossi, EA; Sharkey, RM; Trisal, P, 2015)	0.42
" Future strategies should focus on investigating the immunomodulatory effects of chemotherapy in conjunction with TroVax, understanding the optimal dosing and schedule of the combination, and examining potential predictive biomarkers to determine which patients may benefit from immunotherapy from those who do not."	( TroVax in colorectal cancer. Cen, P; Rowe, J, 2014)	0.4
" The treatment effects of sequential 5-FU dosing following IrC™ are additive with no additional toxicity in contrast to previous studies where concurrent 5-FU and IrC™ treatment exacerbated 5-FU toxicity."	( Irinophore C™, a lipid nanoparticulate formulation of irinotecan, improves vascular function, increases the delivery of sequentially administered 5-FU in HT-29 tumors, and controls tumor growth in patient derived xenografts of colon cancer. Anantha, M; Bally, MB; Gill, N; Karim, T; Neijzen, R; Ng, SS; Strutt, D; Tai, IT; Wang, H; Waterhouse, D; Wong, MQ; Yapp, DT, 2015)	0.42
" Data simulations were used to interrogate various dosing regimens and give dosing recommendations."	( Integrative population pharmacokinetic and pharmacodynamic dose finding approach of the new camptothecin compound namitecan (ST1968). Barbieri, P; Cresta, S; Delmonte, A; Fasolo, A; Gallerani, E; Gianni, L; Hess, D; Joerger, M; Pace, S; Sessa, C, 2015)	0.64
" A distinct relationship was found between drug exposure and haematological toxicity, supporting flat-dosing once every 3 weeks as the most adequate dosing regimen."	( Integrative population pharmacokinetic and pharmacodynamic dose finding approach of the new camptothecin compound namitecan (ST1968). Barbieri, P; Cresta, S; Delmonte, A; Fasolo, A; Gallerani, E; Gianni, L; Hess, D; Joerger, M; Pace, S; Sessa, C, 2015)	0.64
" Our own data as well as data from the literature was used to calculate those R levels revealing that the formation of 5'-DFUR - the immediate precursor of 5-fluorouracil - was not affected by concomitant medication within the dosing range investigated."	( A simple method for comparing enzymatic capecitabine activation in various mono- and combination chemotherapies. Baroian, N; Buchner, P; Czejka, M; Dittrich, C; Sahmanovic, A; Schreiber, V, 2015)	0.42
" Alternative dosing schedules of SN38-TS NPs were compared to irinotecan."	( Nanoparticle delivery of an SN38 conjugate is more effective than irinotecan in a mouse model of neuroblastoma. Alferiev, IS; Brodeur, GM; Chorny, M; Croucher, JL; Iyer, R; Kolla, V; Levy, RJ; Mangino, JL, 2015)	0.42
" Due to frequent skipping of day 8 dosing for cytopenias, the study was expanded to test namitecan dosing on day 1 every 21 days (D1-Q21) at a starting dose of 17."	( Phase-I dose finding and pharmacokinetic study of the novel hydrophilic camptothecin ST-1968 (namitecan) in patients with solid tumors. Barbieri, P; Delmonte, A; Gallerani, E; Hess, D; Joerger, M; Pace, S; Sessa, C, 2015)	0.65
"5, 20 mg dosing cohorts), 29 patients into the D1-21D group (17."	( Phase-I dose finding and pharmacokinetic study of the novel hydrophilic camptothecin ST-1968 (namitecan) in patients with solid tumors. Barbieri, P; Delmonte, A; Gallerani, E; Hess, D; Joerger, M; Pace, S; Sessa, C, 2015)	0.65
" An adaptive reduction in chemotherapy dosage was required in 2 patients due to hematological toxicity, and a delay in chemotherapy cycles was required for 3 patients."	( FOLFIRI plus bevacizumab as a second-line therapy for metastatic intrahepatic cholangiocarcinoma. Bengrine, L; Ghiringhelli, F; Guion-Dusserre, JF; Lorgis, V; Vincent, J, 2015)	0.42
" Our results indicate that to have the most synergistic anticancer effect, the drugs in the optimized regimen should be dosage specific and ratio specific."	( Optimized combinations of bortezomib, camptothecin, and doxorubicin show increased efficacy and reduced toxicity in treating oral cancer. Ding, X; Matsuo, K; Xu, L; Yang, J; Zheng, L, 2015)	0.69
" Dosing decisions were based on the probability of experiencing a dose-limiting toxicity (DLT) during the first two 21-day treatment cycles."	( Phase I study of everolimus, cetuximab and irinotecan as second-line therapy in metastatic colorectal cancer. Beck, JT; Brandt, U; Davidson, SJ; Garrett, CR; Hecht, JR; Mackenzie, MJ; Reid, TR; Rizvi, S; Sharma, S, 2015)	0.42
" Additional studies should evaluate the effect of nomogram-guided dosing on efficacy in patients receiving irinotecan."	( An internally and externally validated nomogram for predicting the risk of irinotecan-induced severe neutropenia in advanced colorectal cancer patients. Ando, Y; Fujita, K; Ichikawa, W; Minamimura, K; Miyauchi, H; Morita, S; Moriwaki, T; Nakamura, M; Ohashi, Y; Okutani, Y; Sadahiro, S; Sakata, Y; Shinozaki, K; Sugihara, M; Sugiyama, T; Takahashi, T; Takii, Y; Tanaka, C; Tsuji, A; Uehara, K, 2015)	0.42
" Clinically relevant dosing schemes of IMMU-132 administered either every other week, weekly, or twice weekly in mice bearing human pancreatic or gastric cancer xenografts demonstrate similar, significant antitumor effects in both models."	( Sacituzumab Govitecan (IMMU-132), an Anti-Trop-2/SN-38 Antibody-Drug Conjugate: Characterization and Efficacy in Pancreatic, Gastric, and Other Cancers. Arrojo, R; Cardillo, TM; Chang, CH; Goldenberg, DM; Govindan, SV; Liu, D; Rossi, EA; Sharkey, RM; Trisal, P, 2015)	0.42
" Doxycycline (Dox)-induced overexpression of Myc-ELAS1 caused γ-irradiation to induce apoptosis in human osteosarcoma (U2OS) cells, at 1/10th the effective dosage of γ-irradiation required for apoptosis in Myc-vector-expressing cells; ELAS1 peptide incorporation into U2OS cells also showed similar apoptotic effects."	( ELAS1-mediated inhibition of the cyclin G1-B'γ interaction promotes cancer cell apoptosis via stabilization and activation of p53. Mukai, S; Naito, Y; Nojima, H; Ohno, S; Yabuta, N, 2015)	0.42
" Using genomic biomarkers, patients at high risk for developing side effects can be distinguished before initiating medical treatment, allowing the choice of an appropriate drug/initial dosage regimen."	( [Utilization of Genomic Biomarkers for Post-marketing Safety of Drugs]. Kaniwa, N, 2015)	0.42
"The current work integrates cell-cycle dynamics occurring in the bone marrow compartment as a key element in the structure of a semimechanistic pharmacokinetic/pharmacodynamic model for neutropenic effects, aiming to describe, with the same set of system- and drug-related parameters, longitudinal data of neutropenia gathered after the administration of the anticancer drug diflomotecan (9,10-difluoro-homocamptothecin) under different dosing schedules to patients (n = 111) with advanced solid tumors."	( Semimechanistic cell-cycle type-based pharmacokinetic/pharmacodynamic model of chemotherapy-induced neutropenic effects of diflomotecan under different dosing schedules. Buil-Bruna, N; Garrido, MJ; Mangas-Sanjuan, V; Soto, E; Trocóniz, IF, 2015)	0.58
" No difference in other treatment toxicity was observed between the two groups, and patients exhibited high compliance in dosing administration."	( Double-blind, placebo-controlled, randomized phase II study of TJ-14 (Hangeshashinto) for infusional fluorinated-pyrimidine-based colorectal cancer chemotherapy-induced oral mucositis. Aoyama, T; Kataoka, M; Kono, T; Matsuda, C; Mishima, H; Morita, S; Munemoto, Y; Nagata, N; Oshiro, M; Sakamoto, J, 2015)	0.42
"0 on day 1) every 3 weeks, with 3-6 patients treated at each irinotecan dosage level (levels I-IV)."	( Weekly irinotecan combined with carboplatin for patients with small-cell lung cancer: A phase I study. Inoue, A; Ishimoto, O; Maemondo, M; Nukiwa, T; Sugawara, S, 2015)	0.42
" Thus, irinotecan dosage should be closely monitored for effective and safe chemotherapy in obese cancer patients who are at a higher risk of developing liver toxicity."	( Impact of obesity on accumulation of the toxic irinotecan metabolite, SN-38, in mice. Gandhi, A; Ghose, R; Mallick, P; Shah, P, 2015)	0.42
"Female nude mice were intracranially or intracardially implanted with human brain seeking breast cancer cells (MDA-MB-231Br) and dosed with irinotecan or NKTR-102 to determine plasma and tumor pharmacokinetics of irinotecan and SN38."	( NKTR-102 Efficacy versus irinotecan in a mouse model of brain metastases of breast cancer. Adkins, CE; Eldon, MA; Hoch, U; Hye, T; Lockman, PR; Mohammad, AS; Mohan, NK; Nounou, MI; Terrell-Hall, T, 2015)	0.42
" Because of its amphiphilic nature, the CPT-FUDR conjugate self-assembled into stable nanoparticles which could simultaneously release fixed dosage of the two drugs in cancer cells."	( Synergistic Combination Chemotherapy of Camptothecin and Floxuridine through Self-Assembly of Amphiphilic Drug-Drug Conjugate. Hu, M; Huang, P; Su, Y; Wang, Y; Yan, D; Zhou, L; Zhu, X, 2015)	0.68
"Because the serum concentration of 5-FU fluctuates and displays various patterns, the dosage should not be based on body surface area."	( Fluctuation in Plasma 5-Fluorouracil Concentration During Continuous 5-Fluorouracil Infusion for Colorectal Cancer. Higashida, M; Hirai, T; Kubota, H; Matsumoto, H; Murakami, H; Okumura, H; Tohyama, K; Tsuruta, A, 2015)	0.42
" We confirmed in these studies that after completion of the Q7D×3 dosing of IrC™, but not IRN, the tumor-associated vascular was normalized as compared to untreated tumors."	( Determination of an optimal dosing schedule for combining Irinophore C™ and temozolomide in an orthotopic model of glioblastoma. Anantha, M; Backstrom, I; Bally, MB; Chu, F; Kalra, J; Masin, D; Strutt, D; Verreault, M; Walker, D; Waterhouse, D; Wehbe, M; Yapp, DT, 2015)	0.42
" This review first summarizes the roles of irinotecan in chemotherapy for metastatic CRC and then discusses the optimal dosing of irinotecan based on the aforementioned factors affecting systemic exposure to SN-38, with the ultimate goal of achieving personalized irinotecan-based chemotherapy."	( Irinotecan, a key chemotherapeutic drug for metastatic colorectal cancer. Fujita, K; Ishida, H; Kubota, Y; Sasaki, Y, 2015)	0.42
" On the 7th day, the mice were euthanized, and intestinal samples were collected for histopathology and morphometric analysis, as well as for the determination of myeloperoxidase activity and cytokine dosage (TNF-α and IL-6)."	( A new animal model of intestinal mucositis induced by the combination of irinotecan and 5-fluorouracil in mice. Almeida, PR; Assis-Júnior, EM; Brito, GA; Lima-Júnior, RC; Melo, AT; Pereira, VB; Ribeiro, RA; Wong, DV, 2016)	0.43
" Twice-daily oral dosing of veliparib (10-50 mg) occurred on days 3 to 14 (cycle 1) and days -1 to 14 (subsequent cycles) followed by a 6-day rest."	( Phase I Safety, Pharmacokinetic, and Pharmacodynamic Study of the Poly(ADP-ribose) Polymerase (PARP) Inhibitor Veliparib (ABT-888) in Combination with Irinotecan in Patients with Advanced Solid Tumors. Bell, T; Boerner, JL; Boerner, SA; Bowditch, A; Burger, A; Cai, D; Chen, AP; Cleary, JM; Ferry-Galow, K; Heilbrun, LK; Ji, J; Kinders, RJ; Li, J; LoRusso, PM; Marrero, AM; Parchment, RE; Pilat, MJ; Rubinstein, L; Sausville, EA; Shapiro, GI; Smith, D; Tolaney, SM; Wolanski, A; Zhang, J; Zhang, Y, 2016)	0.43
"DS-8201a exhibited a HER2 expression-dependent cell growth-inhibitory activity and induced tumor regression with a single dosing at more than 1 mg/kg in a HER2-positive gastric cancer NCI-N87 model."	( DS-8201a, A Novel HER2-Targeting ADC with a Novel DNA Topoisomerase I Inhibitor, Demonstrates a Promising Antitumor Efficacy with Differentiation from T-DM1. Abe, Y; Agatsuma, T; Aida, T; Arakawa, S; Atsumi, R; Hagihara, K; Harada, N; Hayakawa, I; Hirai, T; Ishii, C; Nakada, T; Ogitani, Y; Oitate, M; Okamoto, H; Soma, M; Yamaguchi, J, 2016)	0.43
" We discuss the possible reasons why the pharmacological advantages of carrier-mediated chemotherapy did not translate into enhanced clinical efficacy including the role of the enhanced permeability and retention (EPR) effect and the tumor microenvironment, the optimal dosing regimen for carrier-mediated agents, and the lack of standardization in the conduct and reporting of preclinical studies evaluating anticancer efficacy of these agents."	( Meta-analysis of clinical and preclinical studies comparing the anticancer efficacy of liposomal versus conventional non-liposomal doxorubicin. Alzghari, SK; Chee, W; La-Beck, NM; Petersen, GH; Sankari, SS, 2016)	0.43
" Expert commentary: Pending issues that shall be addressed in the upcoming years include the optimization of ramucirumab dosing schedule, assessment of its role with other chemotherapy regimens or in other treatment settings, comparative evaluation of this agent with other antiangiogenics, and identification of predictive biomarkers to improve the therapeutic index and cost-effectiveness of this drug."	( The safety and efficacy of ramucirumab for the treatment of metastatic colorectal cancer. Diaz-Serrano, A; Garcia-Carbonero, R; Riesco-Martinez, MC, 2016)	0.43
" This platform, which utilizes a 3D printed fluidic device, allows for dynamic dosing of three dimensional cell cultures, also known as spheroids."	( Drug penetration and metabolism in 3D cell cultures treated in a 3D printed fluidic device: assessment of irinotecan via MALDI imaging mass spectrometry. Heller, AA; Hummon, AB; LaBonia, GJ; Lockwood, SY; Spence, DM, 2016)	0.43
" The subsequent free-flowing, SLH solid dosage form contained high loading levels of molecularly dispersed SN38 (5%w/w) and significantly enhanced in vitro dissolution in simulated gastrointestinal media."	( Facilitating gastrointestinal solubilisation and enhanced oral absorption of SN38 using a molecularly complexed silica-lipid hybrid delivery system. Bala, V; Prestidge, CA; Rao, S, 2016)	0.43
" This relationship favors new treatment strategies with white blood cell growth factors or chemotherapy dosing based on muscle value."	( Sarcopenia is Associated with Chemotherapy Toxicity in Patients Undergoing Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis from Colorectal Cancer. Ammari, S; Antoun, S; Bayar, MA; Chemama, S; Elias, D; Goéré, D; Lanoy, E; Raynard, B; Stoclin, A, 2016)	0.43
" In consideration of the long-term biological toxicity, the prodrug nanoparticles with higher drug content exhibit more excellent anticancer efficiency due to that lower dosage of them are enough for effectively killing HeLa cells."	( Fabrication of Reductive-Responsive Prodrug Nanoparticles with Superior Structural Stability by Polymerization-Induced Self-Assembly and Functional Nanoscopic Platform for Drug Delivery. Hong, CY; Pan, CY; Zhang, WJ, 2016)	0.43
" In these situations, instead of determining a dose that works for every patient, the trial aims to identify a dosing algorithm that prescribes dose according to the patient's biomarker or pharmacokinetic expression."	( Sequential designs for individualized dosing in phase I cancer clinical trials. Cheung, YK; Mao, X, 2017)	0.46
" The dose of S-1 was escalated in a stepwise fashion from 40 (level 1) to 60 mg/m (level 2) and then 80 mg/m (level 3), whereas the dosage of irinotecan remained the same (150 mg/m)."	( Phase I Clinical Study of Irinotecan Plus S-1 in Patients With Advanced or Recurrent Cervical Cancer Previously Treated With Platinum-Based Chemotherapy. Kimura, T; Kobayashi, E; Kozasa, K; Mabuchi, S; Owa, T; Tomimatsu, T; Tsutui, T; Yamashita, M; Yoki, T; Yokoi, E, 2016)	0.43
" In vitro cytotoxicity evaluation and in vivo tumor suppression with low dosage drugs further demonstrated the favorable potency of the redox-responsive nanoplatform in tumor combination chemotherapy."	( Visible light-induced crosslinking and physiological stabilization of diselenide-rich nanoparticles for redox-responsive drug release and combination chemotherapy. Hu, X; Hu, Y; Wu, B; Xing, D; Zhai, S, 2017)	0.46
" Essentially no differences between wall-deficient and wild-type cells were observed with respect to dose-response and time-course of camptothecin and mastoparan."	( The Cytotoxic Effects of Camptothecin and Mastoparan on the Unicellular Green Alga Chlamydomonas reinhardtii. Morawski, M; Voigt, J; Wöstemeyer, J, 2017)	0.96
" Using a genetically engineered model of NSCLC arising from induced mutation of KRas and knockout of Trp53, we continuously dosed mice with STA-8666 from immediately after tumor induction for 15 weeks."	( Tumor-targeted SN38 inhibits growth of early stage non-small cell lung cancer (NSCLC) in a KRas/p53 transgenic mouse model. Deneka, AY; Gaponova, AV; Golemis, EA; Haber, L; Kopp, MC; Nikonova, AS, 2017)	0.46
" The influence of pH, the time of polymerization, and the dosage of the drug on particle size and encapsulation efficiency (EE) were studied."	( Enhanced oral bioavailability of 10-hydroxycamptothecin through the use of poly (n-butyl cyanoacrylate) nanospheres. Asghar, S; Chen, Z; Jin, X; Li, H; Li, Y; Liu, J; Ping, Q; Xiao, Y; Zhu, X, 2017)	0.72
" The authors performed a phase 2 cooperative group study (North Central Cancer Treatment Group N0543, Alliance) using genotype-dosed capecitabine, irinotecan, and oxaliplatin (gCAPIRINOX), with dosing assigned based on UDP glucuronosyltransferase family 1 member A1 (UGT1A1) genotype to test: 1) whether the addition of irinotecan would improve outcomes; and 2) whether UGT1A1 genotype-based dosing could optimize tolerability."	( North Central Cancer Treatment Group N0543 (Alliance): A phase 2 trial of pharmacogenetic-based dosing of irinotecan, oxaliplatin, and capecitabine as first-line therapy for patients with advanced small bowel adenocarcinoma. Ames, MM; Foster, NR; Goetz, MP; Hobday, TJ; Horvath, LE; Jatoi, A; Mahoney, MR; McWilliams, RR; Meyers, JP; Murray, JA; Schneider, DJ; Smyrk, TC, 2017)	0.46
"Previously untreated patients with advanced small bowel adenocarcinoma received irinotecan (day 1), oxaliplatin (day 1), and capecitabine (days 2-15) in a 21-day cycle and were dosed with gCAPIRINOX according to UGT1A1*28 genotypes (6/6, 6/7, and 7/7)."	( North Central Cancer Treatment Group N0543 (Alliance): A phase 2 trial of pharmacogenetic-based dosing of irinotecan, oxaliplatin, and capecitabine as first-line therapy for patients with advanced small bowel adenocarcinoma. Ames, MM; Foster, NR; Goetz, MP; Hobday, TJ; Horvath, LE; Jatoi, A; Mahoney, MR; McWilliams, RR; Meyers, JP; Murray, JA; Schneider, DJ; Smyrk, TC, 2017)	0.46
"UGT1A1 genotype-directed dosing (gCAPIRINOX) appears to be feasible with favorable rates of hematologic toxicity compared with prior 3-drug studies in unselected patients."	( North Central Cancer Treatment Group N0543 (Alliance): A phase 2 trial of pharmacogenetic-based dosing of irinotecan, oxaliplatin, and capecitabine as first-line therapy for patients with advanced small bowel adenocarcinoma. Ames, MM; Foster, NR; Goetz, MP; Hobday, TJ; Horvath, LE; Jatoi, A; Mahoney, MR; McWilliams, RR; Meyers, JP; Murray, JA; Schneider, DJ; Smyrk, TC, 2017)	0.46
"Purpose The objectives were to evaluate dosing schedules of labetuzumab govitecan, an antibody-drug conjugate targeting carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) for tumor delivery of 7-ethyl-10-hydroxycamptothecin (SN-38), in an expanded phase II trial of patients with relapsed or refractory metastatic colorectal cancer."	( Phase I/II Trial of Labetuzumab Govitecan (Anti-CEACAM5/SN-38 Antibody-Drug Conjugate) in Patients With Refractory or Relapsing Metastatic Colorectal Cancer. Berlin, JD; Cohen, SJ; Dotan, E; Goldberg, RM; Goldenberg, DM; Govindan, SV; Guarino, MJ; Hecht, JR; Lieu, CH; Marshall, JL; Messersmith, WA; Sharkey, RM; Simpson, PS; Starodub, AN; Wegener, WA, 2017)	0.64
" This would allow fine-tuning the dosage according to the patient's metabolism, a key condition to reduce side effects."	( Peptide biosensors for anticancer drugs: Design in silico to work in denaturizing environment. Battisti, A; Berti, F; Buzzo, M; Giodini, L; Gladich, I; Guida, F; Laio, A; Marangon, E; Toffoli, G, 2018)	0.48
" Dosage adjustment occurred in only 3 (30."	( A pilot clinical study of apatinib plus irinotecan in patients with recurrent high-grade glioma: Clinical Trial/Experimental Study. Jiang, X; Li, C; Liang, L; Liu, L; Lu, P; Qiao, Y; Wang, L; Xia, Y; Yang, T, 2017)	0.46
"At present, drug dosage is based on standardised approaches that disregard pharmakokinetic differences between patients and lead to non-optimal efficacy and unnecessary side effects."	( pH-Mediated molecular differentiation for fluorimetric quantification of chemotherapeutic drugs in human plasma. Guldin, S; Krol, S; Salvati, E; Serrano, LA; Stellacci, F; Yang, Y, 2018)	0.48
" Other than BSA, which was already accounted by a BSA-based dosing scheme, no other covariates were deemed to have clinical implications."	( Integrated population pharmacokinetics of etirinotecan pegol and its four metabolites in cancer patients with solid tumors. Chia, YL; Eldon, MA; Gordi, T; Hoch, U; Sy, SKB, 2018)	0.48
" Alternatively, the concept of prior dosing allows for the application of dialyzable chemotherapeutic drugs using a normal dose, with an HD followed shortly after to mimic normal renal function."	( Chemotherapeutic agents eligible for prior dosing in pancreatic cancer patients requiring hemodialysis: a systematic review . Egger, J; Hann, A; Hermann, PC; Keller, F; Nosalski, E; Seufferlein, T, 2018)	0.48
" Dosage was more often reduced in patients receiving FOLFOX based therapy."	( Chemotherapy for metastatic colon cancer: No effect on survival when the dose is reduced due to side effects. Evert, M; Fest, P; Fichtner-Feigl, S; Gerken, M; Herr, W; Klinkhammer-Schalke, M; Munker, S; Ott, C; Reng, M; Schlitt, HJ; Schnoy, E; Stroszczynski, C; Teufel, A; Vogelhuber, M; Wiggermann, P, 2018)	0.48
"Contrary to our expectations, the need to reduce chemotherapy dosage due to side effects does not indicate a worse prognosis in our retrospective analysis."	( Chemotherapy for metastatic colon cancer: No effect on survival when the dose is reduced due to side effects. Evert, M; Fest, P; Fichtner-Feigl, S; Gerken, M; Herr, W; Klinkhammer-Schalke, M; Munker, S; Ott, C; Reng, M; Schlitt, HJ; Schnoy, E; Stroszczynski, C; Teufel, A; Vogelhuber, M; Wiggermann, P, 2018)	0.48
" However, to date, in Japan, factors influencing cholinergic symptoms, such as dosage of CPT-11, regular medications, and laboratory values indicating liver function, have not been studied."	( [Factors Affecting Development of Cholinergic Symptoms after Irinotecan Administration]. Ishikura, K; Mizukami, Y; Okuyama, H; Tamura, K, 2018)	0.48
" The individualized dosing of CPT-11 is essential to ensure optimal pharmacotherapy in cancer patients, given the wide interindividual pharmacokinetic variability of this drug and its active metabolite SN-38."	( Population pharmacokinetic model of irinotecan and its metabolites in patients with metastatic colorectal cancer. Aldaz, A; Insausti, A; Oyaga-Iriarte, E; Sayar, O, 2019)	0.51
" Low dosage CPT combined with MV was also found to elicit the same therapeutic effect as high doses of CPT."	( Chemovirotherapeutic Treatment Using Camptothecin Enhances Oncolytic Measles Virus-Mediated Killing of Breast Cancer Cells. Lin, LT; Liu, CH; Pan, YC; Richardson, CD; Tai, CJ; Wong, SH, 2019)	0.79
" In this article, an ultra-high performance liquid chromatography tandem mass spectrometry method for the analysis of 10-hydroxycamptothecin and tetrandrine in plasma has been developed, validated, and utilized to compare the pharmacokinetics of both drugs in the original dosage form and administered as liposome complexes."	( Pharmacokinetics of 10-hydroxycamptothecin-tetrandrine liposome complexes in rat by a simple and sensitive ultra-high performance liquid chromatography with tandem mass spectrometry. Mao, J; Ping, Y; Shuang, R; Wang, M; Zou, J, 2020)	1.05
" When administrated at the same dosage of 10 mg/kg (CPT equivalent), SAPD 1, the one with the lowest CMC, shows the best efficacy in tumor suppression."	( The role of critical micellization concentration in efficacy and toxicity of supramolecular polymers. Anderson, CF; Cui, H; Dai, W; Li, Y; Ran, W; Su, H; Wang, F; Wang, H; Wang, Z; Zhang, P; Zhang, W; Zheng, C, 2020)	0.56
" Given the known sex differences in fluoropyrimidine pharmacokinetics, sex-specific dosing of fluoropyrimidines warrants further investigation."	( Sex and Adverse Events of Adjuvant Chemotherapy in Colon Cancer: An Analysis of 34 640 Patients in the ACCENT Database. Alberts, SR; Allegra, CJ; Andre, T; Blanke, CD; de Gramont, A; Dixon, JG; Francini, E; George, TJ; Goldberg, RM; Grothey, A; Haller, DG; Kerr, R; Marsoni, S; O'Connell, MJ; Saltz, LB; Seitz, JF; Shi, Q; Taieb, J; Twelves, C; VanCutsem, E; Wagner, AD; Wolmark, N; Yothers, G, 2021)	0.62
"Findings will provide timely information on the safety, efficacy, and optimal dosing of t-PA to treat moderate/severe COVID-19-induced ARDS, which can be rapidly adapted to a phase III trial (NCT04357730; FDA IND 149634)."	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Xun, J; Yaffe, MB; Yalew, A; Yamamoto, S; Yan, D; Yan, H; Yan, S; Yan, X; Yang, AD; Yang, E; Yang, H; Yang, J; Yang, JL; Yang, K; Yang, M; Yang, P; Yang, Q; Yang, S; Yang, W; Yang, X; Yang, Y; Yao, JC; Yao, WL; Yao, Y; Yaqub, TB; Ye, J; Ye, W; Yen, CW; Yeter, HH; Yin, C; Yip, V; Yong-Yi, J; Yu, HJ; Yu, MF; Yu, S; Yu, W; Yu, WW; Yu, X; Yuan, P; Yuan, Q; Yue, XY; Zaia, AA; Zakhary, SY; Zalwango, F; Zamalloa, A; Zamparo, P; Zampini, IC; Zani, JL; Zeitoun, R; Zeng, N; Zenteno, JC; Zepeda-Palacio, C; Zhai, C; Zhang, B; Zhang, G; Zhang, J; Zhang, K; Zhang, Q; Zhang, R; Zhang, T; Zhang, X; Zhang, Y; Zhang, YY; Zhao, B; Zhao, D; Zhao, G; Zhao, H; Zhao, Q; Zhao, R; Zhao, S; Zhao, T; Zhao, X; Zhao, XA; Zhao, Y; Zhao, Z; Zheng, Z; Zhi-Min, G; Zhou, CL; Zhou, HD; Zhou, J; Zhou, W; Zhou, XQ; Zhou, Z; Zhu, C; Zhu, H; Zhu, L; Zhu, Y; Zitzmann, N; Zou, L; Zou, Y, 2022)	0.72
" Therefore, HCPT-SMEDDS involved designing for the ease of manufacture, and provided a potent oral dosage form for preserving its active lactone form as well as enhancing the dissolution rate."	( Enhanced Stability of the Pharmacologically Active Lactone Form of 10-Hydroxycamptothecin by Self-Microemulsifying Drug Delivery Systems. Feng, M; Lai, B; Li, R; Wang, Y; Yang, Q; Zhou, X, 2020)	0.79
" Dose-response projections suggested an increase in ORR (67."	( Exposure-Response Relationships in Patients With HER2-Positive Metastatic Breast Cancer and Other Solid Tumors Treated With Trastuzumab Deruxtecan. AbuTarif, M; Garimella, T; Iwata, H; Kastrissios, H; LaCreta, F; Lee, C; Lin, CC; Shahidi, J; Tamura, K; Wada, R; Watanabe, J; Yin, O; Zhang, L, 2021)	0.62
"FOLFIRINOX and FOLFOXIRI are combination chemotherapy treatments that incorporate the same drug cocktail (folinic acid, 5-fluorouracil, oxaliplatin and irinotecan) but exploit an altered dosing regimen when used in the management of pancreatic and colorectal cancer, respectively."	( A single microbubble formulation carrying 5-fluorouridine, Irinotecan and oxaliplatin to enable FOLFIRINOX treatment of pancreatic and colon cancer using ultrasound targeted microbubble destruction. Callan, B; Callan, JF; Gao, J; Griffith, DM; Logan, KA; Love, M; McHale, AP; McKaig, T; Nesbitt, H; Taylor, M, 2021)	0.62
" While the recommended dosing schedule for the triplet chemotherapy regimen with 5-fluorouracil, oxaliplatin and irinotecan (FOLFOXIRI) in combination with bevacizumab is well established, the optimal dosing of FOLFOXIRI in combination with anti-EGFR agents is unknown."	( Triplet chemotherapy in combination with anti-EGFR agents for the treatment of metastatic colorectal cancer: Current evidence, advances, and future perspectives. Cremolini, C; Esser, R; Falcone, A; Folprecht, G; Martinelli, E; Mazard, T; Modest, DP; Tsuji, A, 2022)	0.72
"To determine the safety, feasibility, pharmacokinetics, and cost of UGT1A1 genotype-guided dosing of irinotecan."	( UGT1A1 genotype-guided dosing of irinotecan: A prospective safety and cost analysis in poor metaboliser patients. Bins, S; Creemers, GJ; de Man, FM; de With, M; Deenen, MJ; Deiman, BALM; Gelderblom, H; Guchelaar, HJ; Houterman, S; Houtsma, D; Hövels, AM; Hulshof, EC; Koolen, SLW; Laven, MMJ; Luelmo, SAC; Mathijssen, RHJ; McLeod, HL; Shulman, K; Swen, JJ; Thijs, AMJ; van Schaik, RHN, 2022)	0.72
" Systemic exposure of SN-38 of reduced dosing in UGT1A1 PMs was still slightly higher compared to a standard-dosed irinotecan patient cohort (difference: +32%)."	( UGT1A1 genotype-guided dosing of irinotecan: A prospective safety and cost analysis in poor metaboliser patients. Bins, S; Creemers, GJ; de Man, FM; de With, M; Deenen, MJ; Deiman, BALM; Gelderblom, H; Guchelaar, HJ; Houterman, S; Houtsma, D; Hövels, AM; Hulshof, EC; Koolen, SLW; Laven, MMJ; Luelmo, SAC; Mathijssen, RHJ; McLeod, HL; Shulman, K; Swen, JJ; Thijs, AMJ; van Schaik, RHN, 2022)	0.72
"UGT1A1 genotype-guided dosing significantly reduces the incidence of febrile neutropenia in UGT1A1 PM patients treated with irinotecan, results in a therapeutically effective systemic drug exposure, and is cost-saving."	( UGT1A1 genotype-guided dosing of irinotecan: A prospective safety and cost analysis in poor metaboliser patients. Bins, S; Creemers, GJ; de Man, FM; de With, M; Deenen, MJ; Deiman, BALM; Gelderblom, H; Guchelaar, HJ; Houterman, S; Houtsma, D; Hövels, AM; Hulshof, EC; Koolen, SLW; Laven, MMJ; Luelmo, SAC; Mathijssen, RHJ; McLeod, HL; Shulman, K; Swen, JJ; Thijs, AMJ; van Schaik, RHN, 2022)	0.72
"The literature recommends that reduced dosage of CPT-11 should be applied in patients with UGT1A1 homozygous mutations, but the impact of UGT1A1 heterozygous mutations on the adverse reactions of CPT-11 is still not fully clear."	( Characteristics and Clinical Implication of UGT1A1 Heterozygous Mutation in Tumor. Cao, B; Gu, Y; Li, Q; Liang, L; Liu, W; Liu, Y; Sun, H; Sun, T; Wang, Q; Xiao, Y; Yao, Y; Yi, F; Yin, W; Yu, J; Zhang, H, 2022)	0.72
"005), and the other adverse reactions spectrum was similar to that of the whole patient cohort, and efficacy and prognosis were similar between patients with different genotypes and patients treated with reduced CPT-11 dosage or not."	( Characteristics and Clinical Implication of UGT1A1 Heterozygous Mutation in Tumor. Cao, B; Gu, Y; Li, Q; Liang, L; Liu, W; Liu, Y; Sun, H; Sun, T; Wang, Q; Xiao, Y; Yao, Y; Yi, F; Yin, W; Yu, J; Zhang, H, 2022)	0.72
" In colorectal cancer, UGT1A1*6 is significantly related to diarrhea post CPT-11 use, efficacy and prognosis is not affected by various genotypes or CPT-11 dosage reduction."	( Characteristics and Clinical Implication of UGT1A1 Heterozygous Mutation in Tumor. Cao, B; Gu, Y; Li, Q; Liang, L; Liu, W; Liu, Y; Sun, H; Sun, T; Wang, Q; Xiao, Y; Yao, Y; Yi, F; Yin, W; Yu, J; Zhang, H, 2022)	0.72
" The high dosing regimen allowed the clinical dose to reach the majority of cancer cells, which has been linked to improved efficacy."	( Antibody-Drug Conjugate Sacituzumab Govitecan Drives Efficient Tissue Penetration and Rapid Intracellular Drug Release. Cardillo, TM; Donnell, J; Govindan, SV; Hofsess, S; Kopp, A; Thurber, GM, 2023)	0.91
" SNSS NAs have demonstrated a passive targeting effect on tumor tissues, a superior antitumor effect compared to irinotecan (CPT-11), and satisfactory biocompatibility with double dosage treatment."	( Disulfide Bond-Based SN38 Prodrug Nanoassemblies with High Drug Loading and Reduction-Triggered Drug Release for Pancreatic Cancer Therapy. Duan, HQ; Duan, XC; Li, XZ; Liu, JT; Qin, N; Zhong, ZX, 2023)	0.91