irinotecan

Research Excerpts

Overview

Irinotecan (IR/CPT-11) is a semisynthetic, water-soluble derivative of the alkaloid camptothecin. It is a topoisomerase inhibitor, widely used in treatment of malignancies including pancreatic ductal adenocarcinoma.

Excerpt	Reference	Relevance
"Irinotecan is a cytotoxic agent that is widely used in the treatment of several types of solid tumors. "	( Elucidating the role of pharmacogenetics in irinotecan efficacy and adverse events in metastatic colorectal cancer patients. Páez, D; Riera, P, 2021)	2.33
"Irinotecan (IRN) is a semisynthetic derivative of camptothecin that acts as a topoisomerase I inhibitor. "	( pH-responsive and folate-coated liposomes encapsulating irinotecan as an alternative to improve efficacy of colorectal cancer treatment. Branco de Barros, AL; Cassali, GD; de Aguiar Ferreira, C; de Alcântara Lemos, J; de Oliveira Silva, J; Fernandes, RS; Miranda, SEM; Nunes, SS; Oliveira, MC; Townsend, DM, 2021)	2.31
"Irinotecan (CPT-11) is a camptothecin chemotherapy drug largely used in treating cancers. "	( Selenium-enriched Bifidobacterium longum DD98 attenuates irinotecan-induced intestinal and hepatic toxicity in vitro and in vivo. Chen, D; Gao, F; Kan, S; Lu, C; Qian, Z; Yin, Y; Zhu, H, 2021)	2.31
"Irinotecan (CPT-11) is an anticancer agent widely used to treat adult solid tumours. "	( Integration of DNA sequencing with population pharmacokinetics to improve the prediction of irinotecan exposure in cancer patients. Bies, RR; Cecchin, E; Cox, NJ; Etheridge, AS; Forrest, A; Innocenti, F; Karas, S; Mathijssen, RHJ; Mohlke, KL; Nickerson, DA; Toffoli, G, 2022)	2.38
"Irinotecan is an anticancer agent widely used for the treatment of solid tumors, including colorectal and pancreatic cancers. "	( All You Need to Know About Innocenti, F; Karas, S, 2022)	2.16
"Irinotecan (IR/CPT-11) is a semisynthetic, water-soluble derivative of the alkaloid camptothecin. "	( Curcumin protects against testis-specific side effects of irinotecan. Aydın, M; Başak, N; Çetin, A; Çiftci, O; Gökhan Turtay, M; Gürbüz, Ş; Oğuztürk, H; Uyanık, Ö; Yücel, N, 2021)	2.31
"Irinotecan is a topoisomerase inhibitor, widely used in treatment of malignancies including pancreatic ductal adenocarcinoma (PDAC) as part of the FOLFIRINOX regimen prescribed as a first-line treatment in several countries. "	( Liposomal irinotecan (Onivyde): Exemplifying the benefits of nanotherapeutic drugs. Innocenti, F; Milano, G; Minami, H, 2022)	2.57
"Irinotecan (Iri) is a key drug to treat metastatic colorectal cancer, but its clinical activity is often limited by de novo and acquired drug resistance. "	( Single cell mass spectrometry studies reveal metabolomic features and potential mechanisms of drug-resistant cancer cell lines. Chen, X; Sun, M; Yang, Z, 2022)	2.16
"Irinotecan (CPT-11) is a camptothecin derivative whose potent anti-tumor activity depends on the rapid formation of an in vivo active metabolite, SN38 (7-ethyl-10-hydroxycamptothecin). "	( A novel irinotecan derivative ZBH-1207 with different anti-tumor mechanism from CPT-11 against colon cancer cells. Li, Y; Shi, W; Wu, D; Yu, H; Zhang, G; Zhao, D; Zhong, B, 2022)	2.6
"Irinotecan is a useful anticancer drug for colorectal cancer treatment. "	( 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)	2.58
"Irinotecan (IRI) is a common chemotherapeutic drug for colorectal cancer; however, the mechanism underlying its immunomodulatory effect remains unclear. "	( Curcumin Suppresses the Progression of Colorectal Cancer by Improving Immunogenic Cell Death Caused by Irinotecan. Fang, Z; Gao, F; Peng, L; Peng, W; Song, F; Zhu, C, 2022)	2.38
"Irinotecan is a chemotherapeutic agent used to treat a variety of tumors, including colorectal cancer (CRC). "	( Irinotecan-gut microbiota interactions and the capability of probiotics to mitigate Irinotecan-associated toxicity. Ahmed, KA; Aidy, SE; Azmy, AF; Dishisha, T; El-Gendy, AO; Hassan, A; Mahdy, MS; Mohamed, WR, 2023)	3.8
"Irinotecan (CPT-11) is an anticancer drug with indications for use in treating various cancers, but severe diarrhea develops as a side effect. "	( Green tea extract prevents CPT-11-induced diarrhea by regulating the gut microbiota. Fukuda, M; Hosoe, T; Ikarashi, N; Kamei, J; Kon, R; Miyaoka, K; Noguchi, H; Sakai, H; Teshima, Y; Tomimoto, R; Yamaguchi, A; Yamaguchi, T, 2023)	2.35
"Irinotecan is a topoisomerase I inhibitor which has been widely used to combat several solid tumors, whereas irinotecan therapy can induce liver injury. "	( Contribution of HIF-1α/BNIP3-mediated autophagy to lipid accumulation during irinotecan-induced liver injury. Shi, C; Wang, Z; Xu, R; Zhang, Y; Zhang, Z, 2023)	2.58
"Irinotecan (CPT-11) is a topoisomerase I inhibitor that was approved for cancer treatment in 1994. "	( Artesunate ameliorates irinotecan-induced intestinal injury by suppressing cellular senescence and significantly enhances anti-tumor activity. Dai, QL; Jia, HJ; Rui Bai, S; Wang, XB; Xia, J; Yue He, S; Zhou, M, 2023)	2.66
"Irinotecan (SN-38) is a potent and broad-spectrum anticancer drug that targets DNA topoisomerase I (Top1). "	( Resistance to TOP-1 Inhibitors: Good Old Drugs Still Can Surprise Us. Kumar, S; Sherman, MY, 2023)	2.35
"Irinotecan is a major chemotherapeutic agent used for SCLC."	( Phase II study of IRInotecan treatment after COmbined chemo-immunotherapy for extensive-stage small cell lung cancer: Protocol of IRICO study. Akagi, K; Dotsu, Y; Fukuda, M; Gyotoku, H; Hayashi, F; Hisamatsu, Y; Ikeda, T; Kinoshita, A; Morinaga, R; Mukae, H; Nagashima, S; Nakatomi, K; Ogata, R; Ono, S; Senju, H; Shimada, M; Soda, H; Sugasaki, N; Tagawa, R; Takemoto, S; Taniguchi, H; Tomono, H; Umeyama, Y, 2023)	1.97
"Irinotecan (CPT-11) is an anti-tumor drug and formulated as nanomedicines to reduce side effects and improve efficacy. "	( Excipient-free nanodispersion of 7-ethyl-10-hydroxycamptothecin exerts potent therapeutic effects against pancreatic cancer cell lines and patient-derived xenografts. Ding, Y; Du, R; Ge, W; Hu, S; Huang, Y; Kong, Y; Shen, Y; Wang, W; Xu, H; Yan, Y; Zhang, L; Zheng, H; Zhou, J; Zhou, Q; Zhou, X, 2019)	1.96
"Irinotecan (CPT-11) is a cytotoxic drug that has wide applicability and usage in cancer treatment. "	( Identify old drugs as selective bacterial β-GUS inhibitors by structural-based virtual screening and bio-evaluations. Chang, S; Chen, Z; Kong, R; Liu, J; Piao, L; Xu, X, 2020)	2
"Irinotecan is a chemotherapeutic drug used in the treatment of advanced colorectal cancer and elevated blood concentrations of its active metabolite, SN-38 leads to increased gastrointestinal (GI) toxicity and diarrhea in patients. "	( Effects of inflammation on irinotecan pharmacokinetics and development of a best-fit PK model. Chityala, PK; Chow, DS; Ghose, R; Wu, L, 2020)	2.3
"Irinotecan (Ir) is a potent antitumor chemotherapeutics in clinic and used for the treatment of a various cancers, but the degree of its application is critically limited by toxic side-effects and marked heterogeneities. "	( Vitamin E-based prodrug self-delivery for nanoformulated irinotecan with synergistic antitumor therapeutics. Hu, Y; Ismail, M; Li, B; Ling, L; Shang, Z, 2020)	2.25
"Irinotecan (CPT-11) is an anticancer agent widely used in the treatment of a variety of adult solid tumors. "	( Optimal Sampling Strategies for Irinotecan (CPT-11) and its Active Metabolite (SN-38) in Cancer Patients. Bies, RR; Cecchin, E; Etheridge, AS; Forrest, A; Innocenti, F; Karas, S; Mathijssen, RHJ; Ramírez, J; Ratain, MJ; Toffoli, G; Tsakalozou, E; van Schaik, RHN, 2020)	2.28
"Irinotecan is a novel anticancer drug that has worked wonders in combination with other anticancer drugs. "	( Irinotecan inducing sinus pause bradycardia in a patient with small round cell cancer. Ambreen, S; Denha, EJ; Lohia, P; Mir, TA; Rahim, A; Shaikhli, RA; Yassin, AS, 2020)	3.44
"Irinotecan (CPT-11) is a valuable chemotherapeutic compound, but its use is associated with severe diarrhea in some patients. "	( Identification of the bioactive components of Banxia Xiexin Decoction that protect against CPT-11-induced intestinal toxicity via UPLC-based spectrum-effect relationship analyses. Chang, XY; Dong, L; Jiang, ZP; Jin, WY; Li, ZZ; Shi, JW; Shi, Y; Sun, H; Wu, JS, 2021)	2.06
"Irinotecan (IRI) is a potent antitumor chemotherapeutic in clinical practice and has been used for treating various malignant tumors, including colorectal cancer (CRC)."	( Combinatorial miRNA-34a replenishment and irinotecan delivery Cui, X; Deng, X; Jia, F; Li, Y; Lu, J; Pan, Z; Shao, L; Wang, X; Wu, Y, 2020)	1.54
"Irinotecan is an anticancer drug for which significant benefits from personalised dosing are expected. "	( A simple, rapid and low-cost spectrophotometric method for irinotecan quantification in human plasma and in pharmaceutical dosage forms. Argyropoulou, A; Gkotzamani, P; Karkalousos, P; Petro, V; Tsotsou, GE, 2021)	2.31
"Irinotecan is an important first- and second-line chemotherapy option for mCRC."	( Optimum patient selection for irinotecan-containing regimens in metastatic colorectal cancer: Literature review and lessons from clinical practice. Basade, M; Mane, A, )	1.14
"Irinotecan (CPT11) is an important drug for small cell lung cancer (SCLC) chemotherapy (CTx). "	( UGT1A1 Gene Polymorphisms in Patients with Small Cell Lung Cancer Treated with Irinotecan-Platinum Doublet Chemotherapy and Their Association with Gastrointestinal Toxicity and Overall Survival. Bandyopadhyay, A; Behera, D; Sharma, S; Singh, N, 2021)	2.29
"Irinotecan is a widely intravenously used drug for the treatment of certain types of solid tumours. "	( Possible roles of intestinal P-glycoprotein and cytochrome P450 3A on the limited oral absorption of irinotecan. Arimori, K; Furuya, Y; Hidaka, M; Kawano, Y; Ono, H; Yamasaki, K, 2021)	2.28
"Irinotecan is a kind of alkaloid with antitumour activity, but its low solubility and high toxicity limit its application. "	( EGCG synergizes the therapeutic effect of irinotecan through enhanced DNA damage in human colorectal cancer cells. Chen, D; Chen, L; Dong, J; Geng, R; Gou, H; Liu, J; Ren, S; Wu, W; Xiang, B; Yang, X; Zhang, Z, 2021)	2.33
"Irinotecan (IRN) is a highly effective chemotherapeutic drug against various types of cancer including colon cancer along with its analogous dose-limiting side effects viz."	( Green tea catechins in combination with irinotecan attenuates tumorigenesis and treatment-associated toxicity in an inflammation-associated colon cancer mice model. Bharali, MK; Borah, G, 2021)	1.61
"Irinotecan (CPT-11) is an important drug used in the treatment of several solid tumor types. "	( Development of an LC-MS/MS Method for Measurement of Irinotecan and Its Major Metabolites in Plasma: Technical Considerations. Aoullay, Z; Cherrah, Y; Lynch, KL; Meddah, B; Van Wijk, XMR; Wu, AHB; Yanhui, M, 2022)	2.41
"Irinotecan is a natural alkaloid agent widely used in cancer therapy. "	( Effect of irinotecan on HMGB1, MMP9 expression, cell cycle, and cell growth in breast cancer (MCF-7) cells. Keyvani-Ghamsari, S; Rabbani-Chadegani, A; Sargolzaei, J; Shahhoseini, M, 2017)	2.3
"Irinotecan (CPT-11) is an effective chemotherapeutic agent widely used to treat different cancers. "	( Improved selectivity and cytotoxic effects of irinotecan via liposomal delivery: A comparative study on Hs68 and HeLa cells. Acedo, P; Cañete, M; Casadó, A; Mora, M; Rello-Varona, S; Sagristá, ML; Stockert, JC; Villanueva, A, 2017)	2.16
"Irinotecan is a prodrug and is often prescribed as part of therapeutic regimes for patients with advanced colorectal cancer."	( MALDI Mass Spectrometry Imaging for Evaluation of Therapeutics in Colorectal Tumor Organoids. Flinders, C; Hummon, AB; Liu, X; Mumenthaler, SM, 2018)	1.2
"Irinotecan (IRI) is a widely used chemotherapeutic drug, mostly used for first-line treatment of colorectal and pancreatic cancer. "	( Pharmacokinetic and Pharmacogenetic Markers of Irinotecan Toxicity. Antunes, MV; Hahn, RZ; Linden, R; Perassolo, MS; Schwartsmann, G; Suyenaga, ES; Verza, SG, 2019)	2.21
"Irinotecan is a key chemotherapeutic agent for the treatment of colorectal (CRC) and pancreatic (PDAC) cancer. "	( Improved Efficacy and Reduced Toxicity Using a Custom-Designed Irinotecan-Delivering Silicasome for Orthotopic Colon Cancer. Chan, R; Chang, CH; Ji, Y; Jiang, J; Liao, YP; Lin, J; Lin, P; Liu, X; Lu, J; Meng, H; Nel, AE; Okene, M; Qiu, W; Tang, I; Wainberg, ZA; Wang, X; Zheng, E, 2019)	2.2
"Irinotecan is a camptothecin analog used worldwide for a broad range of solid tumors, including colorectal cancer. "	( The risk of adverse events of CPT- 11. Ichikawa, W; Imataka, H; Sekikawa, T, 2016)	1.88
"Irinotecan (CPT-11) is a drug used against a wide range of tumor types. "	( Population pharmacokinetic model of irinotecan and its metabolites in patients with metastatic colorectal cancer. Aldaz, A; Insausti, A; Oyaga-Iriarte, E; Sayar, O, 2019)	2.23
"Irinotecan is an anticancer drug with a broad spectrum of activity, characterized by multistep and complex pharmacology. "	( Intestinal bacterial β-glucuronidase as a possible predictive biomarker of irinotecan-induced diarrhea severity. Armand, JP; Chamseddine, AN; Ducreux, M; Mir, O; Paci, A; Paoletti, X; Satar, T, 2019)	2.19
"Irinotecan (CPT‑11) is a DNA topoisomerase I inhibitor which is widely used in clinical chemotherapy, particularly for colorectal cancer treatment. "	( Protective effect of curcumin against irinotecan‑induced intestinal mucosal injury via attenuation of NF‑κB activation, oxidative stress and endoplasmic reticulum stress. Lu, Y; Luo, Z; Ouyang, M; Wu, J; Yao, X; Zhang, W; Zhu, D, 2019)	2.23
"Irinotecan is a strong anticancer drug whose mechanism of action has been reported only for the inhibition of DNA topoisomerase I (Topo I) through its active metabolite SN-38. "	( A novel mechanism of irinotecan targeting MDM2 and Bcl-xL. Chi, SW; Lee, B; Lee, SO; Min, JA; Nashed, A; Yi, GS; Yoo, JC, 2019)	2.28
"Irinotecan (CPT-11) is a drug used against a wide variety of tumors, which can cause severe toxicity, possibly leading to the delay or suspension of the cycle, with the consequent impact on the prognosis of survival. "	( 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)	2.32
"Irinotecan is a major anticancer agent specifically targeting DNA topoisomerase I. "	( Acquired irinotecan resistance is accompanied by stable modifications of cell cycle dynamics independent of MSI status. Bastian, G; Escargueil, AE; Guérin, E; Larsen, AK; Ouaret, D; Petitprez, A; Poindessous, V; Regairaz, M, 2013)	2.25
"Irinotecan is a semisynthetic derivative of camptothecin that exerts potent antitumor activity by inhibiting topoisomerase I. "	( Synthesis, metabolite analysis, and in vivo evaluation of [(11)C]irinotecan as a novel positron emission tomography (PET) probe. Fujinaga, M; Hashimoto, H; Hatori, A; Kawamura, K; Kumata, K; Ogawa, M; Wakizaka, H; Xie, L; Yamasaki, T; Yui, J; Zhang, MR, 2013)	2.07
"Irinotecan is a powerful anticancer drug with severe systemic side effects that limit its clinical application. "	( Irinotecan delivery by microbubble-assisted ultrasound: in vitro validation and a pilot preclinical study. Bouakaz, A; Escoffre, JM; Lecomte, T; Novell, A; Serrière, S, 2013)	3.28
"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)	1.83
"Irinotecan is a key drug in second- or further-line chemotherapy for patients with advanced gastric cancer. "	( A phase II trial of trastuzumab combined with irinotecan in patients with advanced HER2-positive chemo-refractory gastric cancer: Osaka Gastrointestinal Cancer Chemotherapy Study Group OGSG1203 (HERBIS-5). Doki, Y; Furukawa, H; Kudo, T; Kurokawa, Y; Nishikawa, K; Oka, Y; Sakai, D; Satoh, T; Shimokawa, T; Tsujinaka, T, 2013)	2.09
"Irinotecan is a key chemotherapeutic drug used to treat many tumors, including cervical and ovarian cancers; however, irinotecan can cause toxicity, particularly in the presence of uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene polymorphisms, which are associated with reduced enzyme activity. "	( 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)	2.07
"Etirinotecan pegol is a long-acting topoisomerase-I inhibitor designed to provide prolonged tumour-cell exposure to SN38, the active metabolite."	( 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)	1.28
"Irinotecan HCl (CPT-11) is an anticancer prodrug, but there is no available information addressing CPT-11-inhibited leukemia cells in in vitro and in vivo studies. "	( Antitumor effects with apoptotic death in human promyelocytic leukemia HL-60 cells and suppression of leukemia xenograft tumor growth by irinotecan HCl. Chen, YL; Chiang, JH; Chueh, FS; Chung, JG; Hsueh, SC; Lee, CS; Lu, CC; Lu, HF; Yang, JS, 2015)	2.06
"As irinotecan is a P-gp substrate, we tested here whether cetuximab could modify irinotecan concentration in mice."	( Cetuximab increases concentrations of irinotecan and of its active metabolite SN-38 in plasma and tumour of human colorectal carcinoma-bearing mice. Abbara, C; Bonhomme-Faivre, L; Chu, C; Farinotti, R; Gonin, P; Polrot, M; Tandia, M, 2014)	1.19
"Irinotecan is a useful chemotherapeutic for the treatment of various cancers. "	( Inflammasome activation is reactive oxygen species dependent and mediates irinotecan-induced mucositis through IL-1β and IL-18 in mice. Arifa, RD; de Paula, TP; Fagundes, CT; Lima, RL; Madeira, MF; Menezes-Garcia, Z; Rachid, MA; Ryffel, B; Souza, DG; Tavares, LD; Teixeira, MM; Zamboni, DS, 2014)	2.08
"Irinotecan is a topoisomerase I inhibitor approved worldwide as a first- and second-line chemotherapy for advanced or recurrent colorectal cancer (CRC). "	( RNA-seq reveals determinants for irinotecan sensitivity/resistance in colorectal cancer cell lines. Cai, SJ; Huang, LY; Li, XX; Liang, L; Peng, JJ; Shi, DB; Zheng, HT, 2014)	2.13
"Irinotecan is a cytotoxic agent administered by IV infusion in the treatment of advanced colorectal cancer. "	( [Interest of UGT1A1 genotyping within digestive cancers treatment by irinotecan]. Bouquié, R; Boyer, JC; Broly, F; Etienne-Grimaldi, MC; Gagnieu, MC; Gaub, MP; Ged, C; Ghiringhelli, F; Le Guellec, C; Le Morvan, V; Loriot, MA; Philibert, L; Picard, N; Poncet, D; Quaranta, S; Thomas, F, 2014)	2.08
"Irinotecan is a potent inhibitor of deoxyribonucleic acid topoisomerase 1 and the weekly schedule of 100-125 or 350 mg/m(2) administration on Day 1 every 3 weeks is recommended for recurrent small cell lung cancer. "	( Low-dose irinotecan as a second-line chemotherapy for recurrent small cell lung cancer. Goto, K; Matsumoto, S; Morise, M; Niho, S; Ohe, Y; Ohmatsu, H; Umemura, S; Yoh, K, 2014)	2.26
"Irinotecan is a water-soluble camptothecin derivative with clinical activity against colorectal and small cell lung cancers and is currently a standard of care therapeutic in the treatment of colorectal cancer in combination with 5-fluorouracil. "	( Irinophore C™, a lipid nanoparticle formulation of irinotecan, abrogates the gastrointestinal effects of irinotecan in a rat model of clinical toxicities. Anantha, M; Bally, MB; Harasym, N; Manisali, I; Masin, D; Osooly, M; Ostlund, C; Santos, ND; Strutt, D; Sutherland, BW; Waterhouse, DN; Webb, MS; Wehbe, M, 2014)	2.1
"Irinotecan (IRI) is a broad spectrum chemotherapeutic agent used individually or in combination to treat multiple malignancies. "	( Polypeptide-based Micelles for Delivery of Irinotecan: Physicochemical and In vivo Characterization. Cho, HJ; Choi, HG; Choi, JY; Kim, JO; Ramasamy, T; Shin, BS; Umadevi, SK; Yong, CS, 2015)	2.12
"Irinotecan is a topoisomerase 1 inhibitor used for decades for the treatment of colorectal cancer."	( A phase II study of weekly irinotecan in patients with locally advanced or metastatic HER2- negative breast cancer and increased copy numbers of the topoisomerase 1 (TOP1) gene: a study protocol. Balslev, E; Brünner, N; Kümler, I; Nielsen, D; Stenvang, J, 2015)	1.44
"Irinotecan is a camptothecin analogue currently used in clinical practice to treat advanced colorectal cancer. "	( FL118, a novel camptothecin derivative, is insensitive to ABCG2 expression and shows improved efficacy in comparison with irinotecan in colon and lung cancer models with ABCG2-induced resistance. Del Rio, M; Gongora, C; Jin, C; Lam, H; Li, F; Ling, X; Wani, M; Welch, J; Westover, D, 2015)	2.07
"Irinotecan is a widely used topoisomerase-I-inhibitor with a very narrow therapeutic window because of its severe toxicity. "	( 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)	2.12
"Irinotecan is an effective drug in the treatment of colorectal cancer. "	( [Examination of UGT1A1 polymorphisms and irinotecan-induced neutropenia in patients with Colorectal cancer]. Azuma, Y; Hanashiro, K; Nakachi, A; Nishiki, T; Ota, M; Shimabuku, M; Shimabukuro, N; Shiroma, H; Teruya, T; Toritsuka, D, 2015)	2.13
"Irinotecan is a cytotoxic agent used widely for the treatment of solid tumors, particularly for metastatic colorectal cancers. "	( ABCC5 and ABCG1 polymorphisms predict irinotecan-induced severe toxicity in metastatic colorectal cancer patients. Cecchin, E; Chen, S; Couture, F; Guillemette, C; Innocenti, F; Jonker, D; Laverdière, I; Lévesque, E; Toffoli, G; Villeneuve, L, 2015)	2.13
"Irinotecan is a cytotoxic agent used in the treatment of metastatic colorectal cancer. "	( Determination of irinotecan and SN38 in human plasma by TurboFlow™ liquid chromatography-tandem mass spectrometry. Authier, N; Durando, X; Eschalier, A; Herviou, P; Libert, F; Pinguet, J; Richard, D; Roche, L, 2016)	2.22
"Irinotecan is a camptothecin analog used worldwide for a broad range of solid tumors, including colorectal and lung cancers. "	( [UGT1A1 Genotyping for Proper Use of Irinotecan]. Ando, Y; Matsuoka, A, 2015)	2.13
"Irinotecan hydrochloride is a camptothecin derivative that exerts antitumor activity against a variety of tumors. "	( Irinotecan, a key chemotherapeutic drug for metastatic colorectal cancer. Fujita, K; Ishida, H; Kubota, Y; Sasaki, Y, 2015)	3.3
"Irinotecan (CPT-11) is a first-line anti-colon cancer drug, however; CPT-11-induced toxicity remains a key factor limiting its clinical application. "	( Irinotecan (CPT-11)-induced elevation of bile acids potentiates suppression of IL-10 expression. Cao, YF; Chen, Q; Chen, Y; Fang, ZZ; Gonzalez, FJ; Jiang, C; Lu, D; Sun, DX; Tanaka, N; Wang, H; Xie, C; Zhang, D, 2016)	3.32
"Irinotecan is a useful chemotherapeutic agent for the treatment of several solid tumors. "	( The reduction of oxidative stress by nanocomposite Fullerol decreases mucositis severity and reverts leukopenia induced by Irinotecan. Arifa, RDN; Barcelos, LS; Garcia, ZM; Krambrock, K; Ladeira, LO; Lima, RL; Madeira, MFM; Paula, TP; Pinheiro, MVB; Pinho, V; Souza, DG; Teixeira, MM; Ÿvila, TV, 2016)	2.08
"Irinotecan is a widely used antineoplastic drug, mostly employed for the treatment of colorectal cancer. "	( 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)	2.1
"Irinotecan (IRT) is an important part of the first- and second-line regimen for metastatic colorectal and some other cancers. "	( Development of polymeric irinotecan nanoparticles using a novel lactone preservation strategy. Choi, HG; Gupta, B; Kim, JO; Poudel, BK; Ramasamy, T; Thapa, RK; Yong, CS; Youn, YS, 2016)	2.18
"Irinotecan is a topo-isomerase-I inhibitor with broad antitumor activity in solid tumors. "	( Clinical and pharmacogenetic factors associated with irinotecan toxicity. Gelderblom, H; Guchelaar, HJ; Kweekel, D, 2008)	2.04
"Irinotecan hydrochloride is an inhibitor of DNA topoisomerase I enzyme by its main active metabolite SN-38. "	( [Prevention of irinotecan hydrochloride-induced diarrhea by oral administration of Lactobacillus casei strain Shirota in rats]. Miya, T; Morimoto, Y; Ooi, K; Sasaki, H, 2008)	2.14
"Irinotecan is a cytotoxic agent with activity against gliomas. "	( A phase II study of thalidomide and irinotecan for treatment of glioblastoma multiforme. Cole, BF; Eskey, CJ; Fadul, CE; Kingman, LS; Meyer, LP; Newton, HB; Pipas, JM; Rhodes, CH; Roberts, DW, 2008)	2.06
"Irinotecan is an active drug in the first and subsequent lines of chemotherapy for patients with advanced colorectal cancer. "	( Irinotecan in the treatment of elderly patients with advanced colorectal cancer. Díaz-Rubio, E; García-Saenz, JA; Puente, J; Sastre, J, 2008)	3.23
"Irinotecan (IRI) is a topoisomerase I inhibitor active as first- or second-line chemotherapy in advanced colorectal cancer (ACRC). "	( Weekly irinotecan plus protracted venous fluorouracil infusion (WI-FI) in advanced colorectal cancer: a phase II study. Bergnolo, P; Berno, E; Biscardi, M; Boglione, A; Comandone, A; Cutin, SC; Dal Canton, O; Garetto, F; Inguì, M; Oliva, C; Pochettino, P, )	2.03
"Irinotecan (CPT-11) is a clinically important anticancer prodrug that requires enzymatic hydrolysis by carboxyesterase to generate the active metabolite SN-38. "	( Local enzymatic hydrolysis of an endogenously generated metabolite can enhance CPT-11 anticancer efficacy. Chen, KC; Prijovich, ZM; Roffler, SR, 2009)	1.8
"Irinotecan is a topoisomerase-I (Top-I) inhibitor used for the treatment of colorectal cancer. "	( Epigenetic mechanisms of irinotecan sensitivity in colorectal cancer cell lines. Cortesi, F; Crea, F; Danesi, R; Del Tacca, M; Gallegos Ruiz, MI; Giovannetti, E; Mey, V; Nannizzi, S; Peters, GJ; Ricciardi, S, 2009)	2.1
"Irinotecan is a chemotherapeutic agent used in the treatment of CRC and has demonstrated synergistic potential when used with radiation."	( Treatment of fluorouracil-refractory patients with liver metastases from colorectal cancer by using yttrium-90 resin microspheres plus concomitant systemic irinotecan chemotherapy. Bower, GD; Briggs, GM; George, J; Goldstein, D; Olver, IN; Pavlakis, N; Price, D; Rossleigh, MA; Tapner, MJ; Taylor, DJ; van Hazel, GA, 2009)	1.27
"Irinotecan is an anti-neoplastic agent that is widely used for treating colorectal and lung cancers, but often causes toxicities such as severe myelosuppression and diarrhea. "	( Single nucleotide polymorphism in ABCG2 is associated with irinotecan-induced severe myelosuppression. Cha, PC; Furuhata, T; Harada, H; Hirata, K; Kawamoto, S; Mushiroda, T; Nakamura, Y; Nishidate, T; Sasaki, K; Shimoyama, R; Shinoda, N; Zembutsu, H, 2009)	2.04
"Irinotecan (CPT-11) is a genotoxic topoisomerase I inhibitor."	( Attenuation of cytogenetic effects by erythropoietin in human lymphocytes in vitro and P388 ascites tumor cells in vivo treated with irinotecan (CPT-11). Chrisafi, S; Digkas, E; Hatzimichail, A; Kareli, D; Lialiaris, T; Mantadakis, E; Passadaki, T; Vargemezis, V, 2010)	1.29
"Irinotecan (CPT-11) is a common chemotherapeutic agent, but it causes side effects, including genotoxicity with damages the DNA of blood cells."	( Genotoxicity of irinotecan and its modulation by vitamins A, C and E in human lymphocytes from healthy individuals and cancer patients. Drozda, R; Grzegorczyk, K; Kontek, R; Sliwiński, M, 2010)	1.43
"Irinotecan is an interesting agent for individualized dosing, given its complex metabolism and increasing knowledge of its pharmacokinetics predictors."	( Individualizing dosing of irinotecan. Innocenti, F; Ratain, MJ, 2010)	1.38
"Irinotecan is a promising anticancer agent for the treatment of childhood cancer unresponsive to conventional chemotherapy. "	( Treatment of childhood sarcoma with irinotecan: bilirubin level as a predictor of gastrointestinal toxicity. Attinà, G; Coccia, P; Riccardi, R; Ruggiero, A; Scalzone, M, 2009)	2.07
"Irinotecan is an anticancer agent that stabilizes topoisomerase I/DNA complexes. "	( In vivo bioassay to detect irinotecan-stabilized DNA/topoisomerase I complexes in rats. Barth, SW; Briviba, K; Esselen, M; Jäger, N; Marko, D; Watzl, B, 2010)	2.1
"Irinotecan is a topoisomerase I interactive agent, widely used in the treatment of metastatic colorectal cancer. "	( Assessment of cyto/genotoxicity of irinotecan in v79 cells using the comet, micronucleus, and chromosome aberration assay. Gamulin, M; Kasuba, V; Rozgaj, R; Trosić, I, 2010)	2.08
"Irinotecan (CPT-11) is a widely used anticancer drug, especially for the treatment of colorectal cancer. "	( Pharmacogenetics of irinotecan disposition and toxicity: a review. Fujita, K; Sparreboom, A, 2010)	2.13
"Irinotecan is a camptothecin analog used as an anticancer drug. "	( Irinotecan pharmacogenomics. Hoskins, JM; Marsh, S, 2010)	3.25
"Irinotecan (CPT-11) is an anticancer drug with a complex in vivo metabolism widely used in the treatment of colon cancer. "	( Fast liquid chromatography-tandem mass spectrometry method for routine assessment of irinotecan metabolic phenotype. Casetta, B; Corona, G; Elia, C; Toffoli, G, 2010)	2.03
"Irinotecan is an S-phase cell cycle specific plant alkaloid."	( A patient with metastatic colon cancer to the liver presenting with cardiac arrest status post receiving combination irinotecan-panitumumab: a case report. Toema, BM, 2010)	1.29
"Irinotecan (CPT-11) is a topoisomerase I inhibitor with activity in metastatic disease."	( A randomized phase III trial of adjuvant chemotherapy with irinotecan, leucovorin and fluorouracil versus leucovorin and fluorouracil for stage II and III colon cancer: a Hellenic Cooperative Oncology Group study. Aravantinos, G; Bafaloukos, D; Bamias, A; Basdanis, G; Dimopoulos, MA; Economopoulos, T; Efstratiou, I; Fountzilas, G; Kafiri, G; Kalofonos, HP; Karanikiotis, C; Karina, M; Klouvas, G; Korantzis, I; Makatsoris, T; Malettou, L; Matsiakou, F; Miliaras, D; Papadimitriou, CA; Papakostas, P; Papaspirou, I; Pectasides, D; Pentheroudakis, G; Pisanidis, N; Samantas, E; Xiros, N, 2011)	1.33
"Irinotecan is a known radiosensitizer with activity in neuroblastoma."	( Phase I study of vincristine, irinotecan, and ¹³¹I-metaiodobenzylguanidine for patients with relapsed or refractory neuroblastoma: a new approaches to neuroblastoma therapy trial. Chesler, L; DuBois, SG; Goodarzian, F; Groshen, S; Hawkins, R; Marachelian, A; Maris, JM; Matthay, KK; Mosse, YP; Shimada, H; Stewart, C; Tagen, M; Tsao-Wei, D; Villablanca, JG; Yanik, G, 2012)	1.39
"Irinotecan is a second-line anticancer drug, but clinical treatment with irinotecan is limited due to its side effects."	( Caspase-mediated pro-apoptotic interaction of panaxadiol and irinotecan in human colorectal cancer cells. Calway, T; Du, GJ; Du, W; He, TC; Somogyi, J; Wang, CZ; Wen, XD; Yuan, CS; Zhang, ZY, 2012)	1.34
"Irinotecan is a major drug for treatment of metastatic colorectal cancer and a promising agent for other applications like gastric cancer. "	( Irinotecan resistance is accompanied by upregulation of EGFR and Src signaling in human cancer models. Larsen, AK; Petitprez, A, 2013)	3.28
"Irinotecan is an active radiosensitizer in preclinical studies and clinical trials in lung cancer."	( Irinotecan, cisplatin, and radiation in esophageal cancer. Ilson, DH; Kelsen, D; Minsky, B, 2002)	2.48
"Irinotecan (CPT-11) is a prodrug of SN-38 and has been registered for the treatment of advanced colorectal cancer. "	( Modulation of irinotecan metabolism by ketoconazole. de Bruijn, P; Kehrer, DF; Mathijssen, RH; Sparreboom, A; Verweij, J, 2002)	2.12
"Irinotecan (CPT-11) is a topoisomerase I inhibitor used in the treatment of metastatic colorectal cancer. "	( Non-linear pharmacokinetics of irinotecan in mice. Canal, P; Chatelut, E; Guichard, S; Rouits, E, 2002)	2.04
"Irinotecan (CPT-11) is an anticancer agent for the treatment of colon cancer. "	( Secreted and tumour targeted human carboxylesterase for activation of irinotecan. de Graaf, M; Gerritsen, WR; Haisma, HJ; Kruyt, FA; Oosterhoff, D; Pinedo, HM; Sone, T; van Beusechem, VW; van der Meulen, IH, 2002)	1.99
"Irinotecan is a first-line chemotherapeutic agent for patients with metastatic colorectal cancer (CRC). "	( Modulators of ceramide metabolism sensitize colorectal cancer cells to chemotherapy: a novel treatment strategy. Bilchik, AJ; Cabot, MC; Litvak, DA, 2003)	1.76
"Irinotecan is a water-soluble derivative of camptothecin, an alkylator originally extracted from the Chinese tree Camptotheca acuminata. "	( The emerging role of irinotecan (CPT-11) in the treatment of malignant glioma in brain tumors. Friedman, HS; Houghton, PJ; Keir, ST, 2003)	2.08
"Irinotecan is an active drug in the treatment of a number of neoplastic diseases and is not concerned with the multidrug-resistance phenotype of tumor cells, a common mechanism of drug inactivation and resistance in patients with RCC."	( A phase II study of irinotecan in patients with advanced renal cell carcinoma. Chevreau, C; Culine, S; Droz, JP; Escudier, B; Fizazi, K; Mery-Mignard, D; Rolland, F, 2003)	1.36
"Irinotecan is a promising new cytotoxic agent in treatment concurrently with radiation therapy in newly diagnosed locally advanced cervical cancer. "	( Concurrent radiation therapy and irinotecan in stage IIIB cervical cancer. Chanslip, Y; Pattaranutaporn, P; Suntornpong, N; Thephamongkhol, K, 2003)	2.04
"Irinotecan (CPT-11) is a chemotherapeutic drug for cancer that causes severe diarrhea by an uncertain mechanism. "	( Irinotecan causes severe small intestinal damage, as well as colonic damage, in the rat with implanted breast cancer. Bowen, JM; Cummins, AG; Gibson, RJ; Inglis, MR; Keefe, DM, 2003)	3.2
"Irinotecan (CPT-11) is a prodrug that is used to treat metastatic colorectal cancer. "	( The relative contributions of carboxylesterase and beta-glucuronidase in the formation of SN-38 in human colorectal tumours. Clarke, S; Dodds, HM; Rivory, LP; Schnitzler, M; Tobin, PJ, )	1.57
"Irinotecan is an effective treatment for metastatic colorectal cancer. "	( Compassionate use programme of irinotecan in colorectal cancer patients in The Netherlands. de Witte, JH; Keizer, HJ; Peters, WG; ten Bokkel Huinink, WW; van Groeningen, CJ; Voest, EE, 2003)	2.05
"Irinotecan is an active radiosensitizer, and trials have evaluated the combination of irinotecan with concurrent radiotherapy."	( Irinotecan in esophageal cancer. Ilson, DH; Minsky, B, 2003)	2.48
"Irinotecan (Campto) is a topoisomerase I inhibitor currently approved for the treatment of metastatic colon cancer. "	( Irinotecan (Campto) in the treatment of pancreatic cancer. Pizzolato, JF; Saltz, LB, 2003)	3.2
"Irinotecan is a water-soluble derivative of camptothecin, which is isolated from a Chinese tree, Camptotheca acuminata; Its effectiveness against neuroblastoma was confirmed by in vivo preclinical studies, and phase I clinical trials in Japan concluded the maximum tolerated dose of this agent is 160-180 mg/m2/day for 3 consecutive days, repeated after 25 days off. "	( Current treatment and future directions in neuroblastoma. Ikeda, H; Kuroiwa, M; Shitara, T; Tsuchida, Y, 2003)	1.76
"Irinotecan is an active drug in colorectal cancer. "	( Continuous infusion of hepatic arterial irinotecan in pretreated patients with colorectal cancer metastatic to the liver. de Greve, J; Giaccone, G; Gruia, G; Pinedo, HM; van Groeningen, CJ; van Riel, JM, 2004)	2.03
"5-FU/irinotecan is a valuable regimen for second-line treatment in 5-FU/platinum-resistant O-G carcinoma."	( Phase II study of irinotecan and 5-fluorouracil/leucovorin in patients with primary refractory or relapsed advanced oesophageal and gastric carcinoma. Assersohn, L; Brown, G; Cunningham, D; Hill, ME; Norman, AR; Oates, J; Ward, C; Waters, JS, 2004)	1.17
"Irinotecan is a topoisomerase I inhibitor previously shown to be active in the treatment of malignant glioma. "	( Phase 1 trial of irinotecan plus BCNU in patients with progressive or recurrent malignant glioma. Affronti, ML; Allen, D; Bigner, DD; Bohlin, C; Friedman, AH; Friedman, HS; Gururangan, S; Herndon, JE; Jackson, S; Lentz, C; Provenzale, JM; Quinn, JA; Reardon, DA; Rich, JN; Sampson, JH; Schweitzer, H; Tourt-Uhlig, S; Vredenburgh, J; Walker, A; Ziegler, K, 2004)	2.11
"Irinotecan is an active cytotoxic agent for various cancers, and is converted to SN-38, its most active metabolite, by carboxylesterase converting enzyme (CCE) in vivo. "	( In vitro conversion of irinotecan to SN-38 in human plasma. Asaka-Amano, Y; Kasahara, Y; Kuriyama, T; Kurosu, K; Matsubara, H; Shingyoji, M; Takiguchi, Y; Tanabe, N; Tatsumi, K; Watanabe-Uruma, R, 2004)	2.08
"Irinotecan (Camptosar) is a derivative of camptothecin, an inhibitor of the nuclear enzyme topoisomerase I."	( Topoisomerase I inhibitors in small-cell lung cancer. The Japanese experience. Horiike, A; Saijo, N, 2004)	1.04
"Irinotecan (Camptosar) is a promising agent in advanced non-small-cell (NSCLC) and small-cell lung cancer (SCLC)."	( Irinotecan in advanced lung cancer: focus on North American trials. Langer, CJ, 2004)	2.49
"Irinotecan (CPT-11) is a widely-used potent anticancer drug that inhibits mammalian DNA topoisomerase I, however overexpression of the ATP-binding cassette transporter ABCG2 can confer cancer cells resistance to SN-38, the active form of CPT-11. "	( Transport of SN-38 by the wild type of human ABC transporter ABCG2 and its inhibition by quercetin, a natural flavonoid. Ikegami, Y; Ishikawa, T; Mitomo, H; Sano, K; Sawada, S; Yoshida, H; Yoshikawa, M, 2004)	1.77
"Irinotecan is an active drug after fluorouracil (FU) failure in patients with colorectal cancer (CRC). "	( Activity of irinotecan, cisplatin and dacarbazine (CPD) combination in previously treated patients with advanced colorectal carcinoma. Akbulut, H; Buyukcelik, A; Demirkazik, A; Icli, F; Onur, H; Utkan, G; Yalcin, B, 2004)	2.15
"Irinotecan is a selective inhibitor of topoisomerase I, an enzyme part of the replication and transcription system of DNA. "	( New approaches to prevent intestinal toxicity of irinotecan-based regimens. Alimonti, A; Cognetti, F; Di Palma, M; Ferretti, G; Gelibter, A; Pavese, I; Rasio, D; Satta, F; Vecchione, A, 2004)	2.02
"Irinotecan is an effective and safe second-line treatment for colorectal cancer."	( A randomised phase II multicentre trial of irinotecan (CPT-11) using four different schedules in patients with metastatic colorectal cancer. Beijnen, JH; Bertelsen, K; Fennelly, D; Garin, A; Glimelius, B; Gruia, G; Kjaer, M; Kuppens, IE; Lefebvre, P; Moiseyenko, V; Mourier, A; Norum, J; Poulsen, JP; Richel, DJ; Schellens, JH; Schoemaker, NE; Sibaud, D; Smaaland, R; Starkhammer, H; ten Bokkel Huinink, WW; Tveit, KM; Voznyi, E, 2004)	1.31
"Irinotecan (CPT-11) is an effective drug in patients with advanced colorectal cancer (CRC). "	( Weekly irinotecan (CPT-11) in 5-FU heavily pretreated and poor-performance-status patients with advanced colorectal cancer. Balcells, M; Benavides, M; Carabantes, F; Cobo, M; García-Alfonso, P; Gil-Calle, S; Graupera, J; Muñoz-Martín, A; Pérez-Manga, G; Villar, E, 2004)	2.22
"Irinotecan is an anticancer drug approved in combination therapy for advanced colorectal cancer. "	( Pharmacogenetics of irinotecan toxicity. Marsh, S; McLeod, HL, 2004)	2.09
"Irinotecan is a topoisomerase I inhibitor that has been approved for use as a first- and second-line treatment for colorectal cancer. "	( Prediction of irinotecan pharmacokinetics by use of cytochrome P450 3A4 phenotyping probes. de Bruijn, P; de Jong, FA; Figg, WD; Friberg, LE; Graveland, WJ; Lepper, ER; Mathijssen, RH; Rietveld, T; Sparreboom, A; van Schaik, RH; Verweij, J, 2004)	2.13
"Irinotecan (CPT-11) is an important anti-cancer agent activated by carboxylesterase (CE). "	( Effect of carboxylesterase inhibition on the anti-tumour effects of irinotecan. Fujii, M; Kasakura, Y; Morishita, Y; Takayama, T, )	1.81
"Irinotecan is a commonly used effective chemotherapeutic agent, causing severe gastrointestinal mucositis and diarrhea."	( Palifermin reduces diarrhea and increases survival following irinotecan treatment in tumor-bearing DA rats. Bowen, JM; Gibson, RJ; Keefe, DM, 2005)	1.29
"Irinotecan (CPT-11) is a chemotherapeutic drug used to treat tumors by acting on malignant cells through inhibition of DNA topoisomerase I and inducing premature apoptosis. "	( Irinotecan-induced colitis. Bouzourene, H; Chaubert, P; Sandmeier, D, 2005)	3.21
"Irinotecan is a cornerstone drug in the management of metastatic colorectal cancer, as demonstrated by several randomized studies proving a survival benefit for the first time. "	( Irinotecan-based regimens in the adjuvant therapy of colorectal cancer. Douillard, JY, 2005)	3.21
"Irinotecan is an analogue of camptothecin, a topoisomerase I inhibitor, that has an important role in the management of advanced colorectal cancer. "	( Severe irinotecan-induced toxicities in a patient with uridine diphosphate glucuronosyltransferase 1A1 polymorphism. Chung, G; Mehra, R; Murren, J; Psyrri, A; Smith, B, 2005)	2.23
"Irinotecan is a topoisomerase I inhibitor that is highly active against small cell lung cancer (SCLC). "	( Irinotecan and etoposide for previously untreated extensive-disease small cell lung cancer: a phase II trial of West Japan Thoracic Oncology Group. Ariyoshi, Y; Fukuda, Y; Fukuoka, M; Isobe, T; Katakami, N; Komuta, K; Kudoh, S; Nakamura, S; Nakano, T; Takada, M; Takada, Y, 2005)	3.21
"Irinotecan (CPT11) is a prodrug activated in humans mainly by carboxylesterase 2 (CES2) generating the SN38 metabolite responsible for the drug efficacy and toxicity. "	( Carboxylesterase isoform 2 mRNA expression in peripheral blood mononuclear cells is a predictive marker of the irinotecan to SN38 activation step in colorectal cancer patients. Biason, P; Buonadonna, A; Cattarossi, G; Cecchin, E; Colussi, A; Corona, G; Frustaci, S; Masier, S; Toffoli, G, 2005)	1.98
"Irinotecan (CPT-11) is a novel antineoplastic agent that takes effect by inhibiting topoisomerase I. "	( Phase II study of a protracted irinotecan schedule in children with refractory or recurrent soft tissue sarcoma. Arcamone, G; Bertolini, P; Bisogno, G; Carli, M; Paolucci, P; Prete, A; Provenzi, M; Riccardi, R; Ruggiero, A; Surico, G, 2006)	2.06
"Irinotecan (CPT-11) is a prodrug that is used to treat metastatic colorectal cancer. "	( The in vitro metabolism of irinotecan (CPT-11) by carboxylesterase and beta-glucuronidase in human colorectal tumours. Aulds, S; Clarke, S; Crawford, M; Eyers, T; Gallagher, J; Lee, S; Rivory, L; Seale, JP; Solomon, M; Tobin, P, 2006)	2.07
"Irinotecan is a standard option for relapsed/refractory advanced colorectal cancer. "	( Single-agent irinotecan as second-line weekly chemotherapy in elderly patients with advanced colorectal cancer. Cordio, S; Rosati, G, )	1.94
"Irinotecan (CPT-11) is a new drug of the camptothecin family which has shown significant activity in the treatment of metastatic colorectal cancer. "	( 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, )	1.82
"Irinotecan (CPT-11) is an important anticancer drug in management of advanced colon cancer. "	( A mechanistic study on altered pharmacokinetics of irinotecan by St. John's wort. Cao, J; Chan, E; Chen, X; Duan, W; Hu, ZP; Huang, M; Wen, JY; Yang, XX; Yu, XQ; Zhou, SF, 2007)	2.03
"Irinotecan is a chemotherapeutic agent which is commonly used in solid tumors, and causes GI mucositis manifested by severe diarrhea."	( 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)	1.31
"Irinotecan (CPT-11) is an inhibitor of DNA topoisomerase I and is clinically effective against several cancers. "	( Role of cytokines (TNF-alpha, IL-1beta and KC) in the pathogenesis of CPT-11-induced intestinal mucositis in mice: effect of pentoxifylline and thalidomide. Brito, GA; Carvalho, SB; Cunha, FQ; Melo, ML; Ribeiro, RA; Silva, JV; Soares, PM; Soares, RC; Souza, MH; Vale, ML, 2008)	1.79
"Irinotecan is a common cytotoxic agent used in advanced colorectal cancers. "	( Establishment of a single-dose irinotecan model of gastrointestinal mucositis. Alvarez, E; Bowen, JM; Finnie, J; Gibson, RJ; Keefe, DM, 2007)	2.07
"Irinotecan is an established therapeutic option in colorectal cancer. "	( Phase II clinical trial for prevention of delayed diarrhea with cholestyramine/levofloxacin in the second-line treatment with irinotecan biweekly in patients with metastatic colorectal carcinoma. Fischbach, W; Flieger, D; Hainke, S; Keller, R; Klassert, C; Kleinschmidt, R, 2007)	1.99
"Irinotecan (CPT-11) is a key drug for the treatment of various cancers. "	( Tumor targeting carboxylesterase fused with anti-CEA scFv improve the anticancer effect with a less toxic dose of irinotecan. Curiel, DT; Harada, A; Harada, T; Kuroki, M; Nakanishi, Y; Sone, T; Takayama, K; Uchino, J, 2008)	2
"Irinotecan is a topoisomerase I inhibitor widely used as an anticancer agent in the treatment of metastatic colon cancer. "	( Altered expression of cell proliferation-related and interferon-stimulated genes in colon cancer cells resistant to SN38. Breil, C; Candeil, L; Conseiller, E; Copois, V; Del Rio, M; Denis, V; Fraslon, C; Gongora, C; Martineau, P; Molina, F; Pau, B; Vezzio, N, 2008)	1.79
"Irinotecan is an important drug for the treatment of solid tumors. "	( 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)	3.23
"Irinotecan is a prodrug converted to the active cytotoxic molecule SN38 predominantly by the action of liver carboxylesterases. "	( DTS-108, a novel peptidic prodrug of SN38: in vivo efficacy and toxicokinetic studies. Arranz, V; Boukaissi, M; Chéné, AS; de Coupade, C; Dubois, V; Fruchart, JS; Kearsey, J; Meyer-Losic, F; Michel, M; Nicolazzi, C; Quinonero, J; Ravel, D; Ribes, F; Tranchant, I; Zoubaa, I, 2008)	1.79
"Irinotecan is a drug commonly used for the treatment of cancer patients, both as a single agent or in combination therapy. "	( UGT1A1*28 and other UGT1A polymorphisms as determinants of irinotecan toxicity. Biason, P; Masier, S; Toffoli, G, 2008)	2.03
"Irinotecan (CPT-11) is a novel topoisomerase I inhibitor with clinical activity in human malignancies. "	( Limited sampling models for simultaneous estimation of the pharmacokinetics of irinotecan and its active metabolite SN-38. Chabot, GG, 1995)	1.96
"Irinotecan (CPT-11) is a novel water-soluble camptothecin derivative selected for clinical testing based on its good in vitro and in vivo activity in various experimental systems, including pleiotropic drug-resistant tumors. "	( 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)	1.98
"Irinotecan (CPT-11) is a camptothecine derivative with antitumor activity and inhibitor of DNA topoisomerase I. "	( [Effect of chemotherapy using irinotecan (CPT-11) against recurrent colorectal cancer]. Fujimura, T; Kanno, M; Kurosaka, Y; Miwa, K; Miyazaki, I; Nishimura, G; Satou, T; Sugiyama, K; Yonemura, Y; Yoshimitsu, Y, 1995)	2.02
"Irinotecan (CPT-11) is a novel water-soluble, semisynthetic derivative of camptothecin, with inhibitory effects on mammalian DNA topoisomerase I, high cytotoxic activity in vitro and anticancer activity in animal models. "	( Phase I and pharmacokinetic study of the camptothecin derivative irinotecan, administered on a weekly schedule in cancer patients. Bugat, R; Chabot, GG; Culine, S; de Forni, M; Extra, JM; Gouyette, A; Madelaine, I; Marty, ME; Mathieu-Boué, A, 1994)	1.97
"Irinotecan (CPT-11) is a camptothecin derivative used for the treatment of cancer. "	( 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)	1.93
"Irinotecan (CPT-11) is a semi-synthetic derivative of camptothecin currently in clinical trials. "	( Experimental antitumor activity and pharmacokinetics of the camptothecin analog irinotecan (CPT-11) in mice. Bissery, MC; Chabot, GG; Lavelle, F; Vrignaud, P, 1996)	1.96
"Irinotecan (CPT-II) is a semisynthetic derivative of camptothecin. "	( Irinotecan. A review of its pharmacological properties and clinical efficacy in the management of advanced colorectal cancer. Markham, A; Wiseman, LR, 1996)	3.18
"Irinotecan (CPT-11) is a new camptothecine derivative presently in development for the treatment of several advanced malignancies. "	( The transformation of irinotecan (CPT-11) to its active metabolite SN-38 by human liver microsomes. Differential hydrolysis for the lactone and carboxylate forms. Haaz, MC; Riché, C; Rivory, LP; Robert, J, 1997)	2.05
"Irinotecan (CPT-11) is a water-soluble analogue of camptothecin showing activity in colon cancer. "	( Metabolism of irinotecan (CPT-11) by human hepatic microsomes: participation of cytochrome P-450 3A and drug interactions. Haaz, MC; Riché, C; Rivory, L; Robert, J; Vernillet, L, 1998)	2.1
"Irinotecan (CPT-11) is a promising antitumor agent, recently approved for use in patients with metastatic colorectal cancer. "	( Genetic predisposition to the metabolism of irinotecan (CPT-11). Role of uridine diphosphate glucuronosyltransferase isoform 1A1 in the glucuronidation of its active metabolite (SN-38) in human liver microsomes. Coffman, BL; Green, MD; Iyer, L; King, CD; Ratain, MJ; Roy, SK; Tephly, TR; Whitington, PF, 1998)	2
"Irinotecan is a water-soluble camptothecin analogue. "	( A risk-benefit assessment of irinotecan in solid tumours. Rowinsky, EK; Siu, LL, 1998)	2.03
"Irinotecan (CPT-11) is a semisynthetic camptothecin derivative with a broad spectrum of anti-tumour activity. "	( Determinants of CPT-11 and SN-38 activities in human lung cancer cells. Boven, E; Dingemans, AM; Giaccone, G; Jansen, WJ; Kedde, MA; Pinedo, HM; van Ark-Otte, J; van der Vijgh, WJ, 1998)	1.74
"Irinotecan (CPT-11) is a new drug active in colorectal cancer. "	( Comparison of the pharmacokinetics and efficacy of irinotecan after administration by the intravenous versus intraperitoneal route in mice. Bugat, R; Canal, P; Chatelut, E; Guichard, S; Lochon, I; Mahjoubi, M, 1998)	1.99
"Irinotecan (CPT-11) is a chemotherapeutic agent that is active in the treatment of a variety of solid tumor malignancies. "	( Interleukin 15 offers selective protection from irinotecan-induced intestinal toxicity in a preclinical animal model. Black, JD; Cao, S; Rustum, YM; Troutt, AB, 1998)	2
"Irinotecan (CPT-11) is a topoisomerase I inhibitor that has been confirmed to be active against a broad spectrum of neoplasms including non-Hodgkin's lymphoma (NHL). "	( Unexpected hepatotoxicities in patients with non-Hodgkin's lymphoma treated with irinotecan (CPT-11) and etoposide. Igarashi, T; Kobayashi, Y; Murayama, T; Ohtsu, T; Sasaki, Y; Tobinai, K, 1998)	1.97
"Irinotecan (CPT-11) is an analogue of 20(S)-camptothecin with promising activity against several tumor types. "	( Pharmacokinetic interrelationships of irinotecan (CPT-11) and its three major plasma metabolites in patients enrolled in phase I/II trials. Armand, JP; Canal, P; Haaz, MC; Lokiec, F; Rivory, LP; Robert, J, 1997)	2.01
"Irinotecan is an effective agent for the treatment of advanced colorectal cancer. "	( Irinotecan: a new antineoplastic agent for the management of colorectal cancer. Cersosimo, RJ, 1998)	3.19
"Irinotecan is a useful addition to the antineoplastic drug family and offers significant efficacy for treatment of patients with fluorouracil-refractory colorectal cancer."	( Irinotecan: a new antineoplastic agent for the management of colorectal cancer. Cersosimo, RJ, 1998)	3.19
"Irinotecan (CPT11) is a synthetic camptothecin-derived DNA topoisomerase I inhibitor. "	( [Irinotecan: various administration schedules, study of drug combinations, phase I experience]. Armand, JP; Boige, V; Raymond, E, 1998)	2.65
"Irinotecan or CPT11 is a topoisomerase 1 inhibitor. "	( [Irinotecan monotherapy in the treatment of colorectal cancers: results of phase II trials]. Peeters, M; Van Cutsem, E, 1998)	2.65
"Irinotecan is a new topoisomerase I inhibitor. "	( [Irinotecan-containing combinations in solid tumors, except colonic carcinomas]. Armand, JP; Couteau, C, 1998)	2.65
"Irinotecan (CPT-11) is a DNA topoisomerase I inhibitor which has shown activity in vitro against several cancer cell lines and some promising clinical responses in phase I and II trials in various solid tumors. "	( In vitro sensitivity of fresh ovarian carcinoma specimens to CPT-11 (irinotecan). O'meara, AT; Sevin, BU, 1999)	1.98
"Irinotecan (CPT-11) is a derivative of the chemotherapeutic agent camptothecin. "	( A review of the clinical experience with irinotecan (CPT-11). Horowitz, RW; Wadler, S; Wiernik, PH, )	1.84
"Irinotecan is a DNA topoisomerase I inhibitor that has a wide spectrum of activity against human tumors in both preclinical and clinical studies. "	( A phase II trial of irinotecan in hormone-refractory prostate cancer. Chapman, Y; Prager, D; Reese, DM; Rosen, PJ; Tchekmedyian, S, )	1.9
"Irinotecan (CPT-11) is an anticancer drug that occasionally produces acute cholinergic side effects. "	( The mechanism for the inhibition of acetylcholinesterases by irinotecan (CPT-11). Dodds, HM; Rivory, LP, 1999)	1.99
"Irinotecan is a camptothecin analog with an active metabolite, SN-38, which inhibits topoisomerase I activity by stabilizing the topoisomerase I-DNA cleavable complex."	( Single-agent gemcitabine and gemcitabine/irinotecan combination (irimogem) in non-small cell lung cancer. Bahadori, HR; Eckardt, JR; Green, MR; Leong, SS; Perkel, JA; Putman, T; Rocha Lima, CM; Safa, AR; Sherman, CA, 1999)	1.29
"Irinotecan (CPT-11) is an anticancer agent widely employed in the treatment of colorectal carcinoma. "	( 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)	2.03
"Irinotecan (CPT-11) is a derivative of the chemotherapeutic agent Camptothecin. "	( [CPT-11 (irinotecan)--evidence from molecular and pharmacological studies and clinical applications]. Ishikawa, N; Isobe, T; Oguri, T, 2000)	2.17
"Irinotecan (CPT-11) is a topoisomerase I inhibitor commonly used in the treatment of colorectal tumors. "	( Characterization of CPT-11 converting carboxylesterase activity in colon tumor and normal tissues: comparison with p-nitro-phenylacetate converting carboxylesterase activity. Bugat, R; Canal, P; Chatelut, E; Guichard, S; Hennebelle, I; Terret, C, 2000)	1.75
"Irinotecan is a topoisomerase I inhibitor that prolongs survival in patients with colorectal cancer refractory to fluorouracil (5-FU) and leucovorin (LV). "	( Irinotecan plus fluorouracil/leucovorin for metastatic colorectal cancer: a new survival standard. Alakl, M; Awad, L; Douillard, JY; Elfring, GL; Gruia, G; Locker, PK; Miller, LL; Pirotta, N; Saltz, LB, 2001)	3.2
"Irinotecan (CPT-11) is a semi-synthetic camptothecin with a broad spectrum of clinical activity. "	( Metabolism of CPT-11. Impact on activity. Rivory, LP, 2000)	1.75
"Irinotecan (Camptosar) is an active chemotherapeutic agent for lung, gastric, esophageal, and colorectal cancers and a potent radiosensitizer. "	( Phase I study of irinotecan and concurrent radiation therapy for upper GI tumors. Ajani, JA; Blumenshein, GR; Fairweather, JS; Feig, BW; Ho, L; Janjan, NA; Komaki, R; Lynch, PM; Pazdur, R; Pisters, PW; Raijman, I; Walsh, GL, 2000)	2.09
"Irinotecan (Camptosar) is a topoisomerase I inhibitor with demonstrated antitumor activity against a wide variety of malignancies. "	( Irinotecan-based combinations for the adjuvant treatment of stage III colon cancer. Saltz, L, 2000)	3.19
"Irinotecan (CPT-11) is an active drug in the treatment of patients with advanced colorectal carcinoma. "	( Irinotecan and chronomodulated infusion of 5-fluorouracil and folinic acid in the treatment of patients with advanced colorectal carcinoma: a phase I study. Aschelter, AM; Comis, S; D'Attino, RM; Dogliotti, L; Garufi, C; Nisticó, C; Perrone, M; Pugliese, P; Tampellini, M; Terzoli, E, 2001)	3.2
"Irinotecan (CPT-11) is a semisynthetic derivative of camptothecine that has proved activity in the treatment of colorectal carcinoma. "	( Hepatic extraction, metabolism, and biliary excretion of irinotecan in the isolated perfused rat liver. Farabos, C; Gires, P; Haaz, MC; Robert, J, 2001)	2
"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)	2.03
"Irinotecan (CPT-11) is an anticancer prodrug. "	( A new metabolite of irinotecan in which formation is mediated by human hepatic cytochrome P-450 3A4. Kaniwa, N; Ozawa, S; Sai, K; Sawada, JI, 2001)	2.08
"Irinotecan (CPT-11) is a potent inhibitor of topoisomerase I, and has demonstrated antitumor activity against metastatic colorectal cancer. "	( [Standard therapy of CPT-11 for colorectal cancer]. Saitoh, S; Sakata, Y, 2001)	1.75
"Irinotecan is a prodrug that is hydrolyzed by carboxylesterase in vivo to form an active metabolite SN-38. "	( Polymorphisms of UDP-glucuronosyltransferase and pharmacokinetics of irinotecan. Ando, Y; Hasegawa, Y; Ichiki, M; Shimokata, K; Sugiyama, T; Ueoka, H, 2002)	1.99
"Irinotecan (CPT-11) is an active agent for the treatment of advanced colorectal cancer and other tumor types, which frequently metastasize in the liver."	( 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)	1.33
"Irinotecan/gemcitabine is a new combination that offers encouraging activity in terms of radiographic and CA 19-9 response and notable 1-year survival in pancreatic cancer. "	( Irinotecan plus gemcitabine induces both radiographic and CA 19-9 tumor marker responses in patients with previously untreated advanced pancreatic cancer. Bruckner, H; Compton, LD; Dudek, A; Eckardt, J; Elfring, GL; Green, MR; Hainsworth, J; Lester, E; Locker, PK; Miller, LL; Miller, W; Rocha Lima, CM; Savarese, D; Saville, W; Yunus, F, 2002)	3.2
"Irinotecan is a drug of the camptothecin family that has proven activity in advanced colon cancer, with about 20% responses in untreated as well as in 5-fluorouracil-resistant tumors. "	( Determinants of the cytotoxicity of irinotecan in two human colorectal tumor cell lines. Agostini, C; Charasson, V; Montaudon, D; Pavillard, V; Richard, S; Robert, J, 2002)	2.03
"Irinotecan (CPT-11) is an active drug in colorectal cancer."	( Irinotecan hepatic arterial infusion chemotherapy for hepatic metastases from colorectal cancer: results of a phase I clinical study. Cantore, M; Fiorentini, G; Giovanis, P; Guadagni, S; Lucchi, SR; Papiani, G, )	2.3
"Irinotecan is a novel antineoplastic agent that works by inhibiting the enzyme, topoisomerase 1. "	( Irinotecan for pediatric solid tumors: the Memorial Sloan-Kettering experience. Calleja, E; Cosetti, M; Gerald, W; Gorlick, R; Healey, JH; Huvos, AG; LaQuaglia, M; Meyers, PA; Trippett, T; Wexler, LH, 2002)	3.2
"Irinotecan (CPT-11) is a topoisomerase I inhibitor with antitumor activity on a wide variety of neoplasms in several preclinical studies, but it showed poor efficacy in patients with nervous system tumors. "	( Antitumoral effect of irinotecan (CPT-11) on an experimental model of malignant neuroectodermal tumor. Morales, C; Vaquero, J; Zurita, M, 2002)	2.07
"Irinotecan (CPT-11) is a water-soluble camptothecin (CPT) derivative that has been recently approved in the United States for patients as a first-line therapy in advanced colorectal cancer. "	( Intestinal transport of irinotecan in Caco-2 cells and MDCK II cells overexpressing efflux transporters Pgp, cMOAT, and MRP1. Guo, A; Luo, FR; Paranjpe, PV; Rubin, E; Sinko, P, 2002)	2.06

Effects

Irinotecan has a highly complex metabolism, including hydrolyzation by carboxylesterases to its active metabolite SN-38, which is 100- to 1000-fold more active compared with irinotecen itself. Irinotacan has an anti-VEGF effect inhibiting endothelial cell proliferation, increasing apoptosis and reducing microvascular density.

Irinotecan has been found a better salvage therapy in patients who are resistant to 5-fluorouracil. The drug has a highly complex metabolism, including hydrolyzation by carboxylesterases to its active metabolite SN-38, which is 100- to 1000-fold more active compared with irinotecen itself.

Excerpt	Reference	Relevance
"Irinotecan has a highly complex metabolism, including hydrolyzation by carboxylesterases to its active metabolite SN-38, which is 100- to 1000-fold more active compared with irinotecan itself."	( Individualization of Irinotecan Treatment: A Review of Pharmacokinetics, Pharmacodynamics, and Pharmacogenetics. Bins, S; de Man, FM; Goey, AKL; Mathijssen, RHJ; van Schaik, RHN, 2018)	1.52
"Irinotecan has a 20% to 25% response rate (RR) in patients with previously treated metastatic breast cancer (MBC). "	( N0436 (Alliance): A Phase II Trial of Irinotecan With Cetuximab in Patients With Metastatic Breast Cancer Previously Exposed to Anthracycline and/or Taxane-Containing Therapy. Advani, PP; Crozier, JA; Hobday, T; Jaslowski, AJ; LaPlant, B; Moreno-Aspitia, A; Perez, EA, 2016)	2.15
"Irinotecan has an important place in the treatment of metastatic colorectal cancer. "	( Current place of high-dose irinotecan chemotherapy in patients with metastatic colorectal cancer. Ducreux, M; Hebbar, M; Ychou, M, 2009)	2.09
"Irinotecan has an anti-VEGF effect inhibiting endothelial cell proliferation, increasing apoptosis and reducing microvascular density which is only limited by irinotecan toxicity levels."	( Irinotecan therapy and molecular targets in colorectal cancer: a systemic review. Ho, YH; Lam, AK; Sebesan, S; Weekes, J, 2009)	2.52
"Irinotecan has an established role in the treatment of metastatic rectal cancer."	( Irinotecan and radiosensitization in rectal cancer. Illum, H, 2011)	2.53
"Irinotecan has a significant anti-tumour activity and acceptable toxicity in patients with relapsed hepatoblastoma and therefore should be considered for the treatment of these patients. "	( Efficacy of irinotecan single drug treatment in children with refractory or recurrent hepatoblastoma--a phase II trial of the childhood liver tumour strategy group (SIOPEL). Brock, P; Brugières, L; Casanova, M; Child, M; Czauderna, P; de Camargo, B; Maibach, R; Morland, B; Pariente, D; Paris, C; Perilongo, G; Plaschkes, J; Roebuck, D; Ronghe, M; Zimmermann, A; Zsíros, J, 2012)	2.2
"Irinotecan has a reported response rate of 10%-20% in such patients."	( The palliative benefit of irinotecan in 5-fluorouracil-refractory colorectal cancer: its prospective evaluation by a Multicenter Canadian Trial. Feld, R; Fields, A; Goel, R; Hedley, D; Jolivet, J; Lee, IM; Maroun, J; Michael, M; Moore, MJ; Oza, A; Pintilie, M, 2002)	1.34
"Irinotecan has an acceptable tolerability profile and is not associated with cumulative toxicities in patients with metastatic CRC; regimens containing irinotecan extend treatment duration and improve survival."	( Irinotecan in the treatment of colorectal cancer. Fuchs, C; Hoff, PM; Mitchell, EP, 2006)	2.5
"Irinotecan-bevacizumab has been recommended in this setting in France after encouraging results of pilot studies."	( The role of irinotecan-bevacizumab as rescue regimen in children with low-grade gliomas: a retrospective nationwide study in 72 patients. Andre, N; Beccaria, K; Bertozzi, AI; Boddaert, N; Bourdeaut, F; Butel, T; Cuinet, A; De Carli, E; de Marcellus, C; Dufour, C; Figarella-Branger, D; Fouyssac, F; Grill, J; Leblond, P; Pasqualini, C; Puget, S; Robert, MP; Tauziède-Espariat, A; Valteau-Couanet, D; Varlet, P, 2022)	1.82
"Irinotecan has been found a better salvage therapy in patients who are resistant to 5-fluorouracil."	( Irinotecan inducing sinus pause bradycardia in a patient with small round cell cancer. Ambreen, S; Denha, EJ; Lohia, P; Mir, TA; Rahim, A; Shaikhli, RA; Yassin, AS, 2020)	2.72
"Irinotecan has been used in the treatment of various malignancies for many years. "	( Irinotecan-Still an Important Player in Cancer Chemotherapy: A Comprehensive Overview. Kciuk, M; Kontek, R; Marciniak, B, 2020)	3.44
"Irinotecan has a highly complex metabolism, including hydrolyzation by carboxylesterases to its active metabolite SN-38, which is 100- to 1000-fold more active compared with irinotecan itself."	( Individualization of Irinotecan Treatment: A Review of Pharmacokinetics, Pharmacodynamics, and Pharmacogenetics. Bins, S; de Man, FM; Goey, AKL; Mathijssen, RHJ; van Schaik, RHN, 2018)	1.52
"Irinotecan (CPT-11) has been approved for the treatment of advanced or metastatic disease either as a single agent or, more commonly, as part of combined chemotherapeutic regimens."	( Irinotecan toxicity during treatment of metastatic colorectal cancer: focus on pharmacogenomics and personalized medicine. Filip, S; Nekvindová, J; Paulík, A, 2020)	2.72
"Irinotecan and topotecan have been widely used as anticancer drugs for the past 20 years. "	( Targeting Topoisomerase I in the Era of Precision Medicine. Pommier, Y; Thomas, A, 2019)	1.96
"Irinotecan (CPT-11) has also shown efficacy in recurrent gliomas monotherapy with moderate response."	( Irinotecan and temozolomide brain distribution: a focus on ABCB1. Beccaria, K; Carpentier, A; Farinotti, R; Fernandez, C; Goldwirt, L, 2014)	2.57
"Irinotecan has synergism with 5-fluorouracil and shows efficacy in advanced breast cancer."	( Irinotecan and capecitabine combination chemotherapy in a patient with triple-negative breast cancer relapsed after adjuvant chemotherapy with anthracycline and taxane. Cho, JM; Go, SI; Jeon, KN; Kang, JH; Kang, MH; Kim, HG; Kim, MJ; Lee, A; Lee, GW; Lee, JH; Lee, US; Lee, WS, 2015)	2.58
"Irinotecan has shown some efficacy in recurrent malignant gliomas."	( Preclinical impact of bevacizumab on brain and tumor distribution of irinotecan and temozolomide. Beccaria, K; Carpentier, A; Farinotti, R; Fernandez, C; Goldwirt, L; Idbaih, A; Labussiere, M; Levasseur, C; Milane, A; Schmitt, C, 2015)	1.37
"Irinotecan has also displayed efficacy in clinical trials of NSCLC."	( Topoisomerase-I PS506 as a Dual Function Cancer Biomarker. Gjerset, RA; Zhao, M, 2015)	1.14
"Irinotecan has a 20% to 25% response rate (RR) in patients with previously treated metastatic breast cancer (MBC). "	( N0436 (Alliance): A Phase II Trial of Irinotecan With Cetuximab in Patients With Metastatic Breast Cancer Previously Exposed to Anthracycline and/or Taxane-Containing Therapy. Advani, PP; Crozier, JA; Hobday, T; Jaslowski, AJ; LaPlant, B; Moreno-Aspitia, A; Perez, EA, 2016)	2.15
"Irinotecan has been used in the first-line treatment of metastatic colorectal cancer. "	( Phosphorylated retinoblastoma protein is a potential predictive marker of irinotecan efficacy for colorectal cancer. Fujiwara, H; Ikai, A; Kishimoto, M; Otsuji, E; Sakai, T; Sowa, Y; Watanabe, M; Yanagisawa, A, 2016)	2.11
"Irinotecan monotherapy has demonstrated efficacy; however, its efficacy appears to be enhanced when used in combination with other chemotherapeutic agents."	( Experience with irinotecan for the treatment of malignant glioma. Desjardins, A; Friedman, HS; Reardon, DA; Vredenburgh, JJ, 2009)	1.42
"Irinotecan has an important place in the treatment of metastatic colorectal cancer. "	( Current place of high-dose irinotecan chemotherapy in patients with metastatic colorectal cancer. Ducreux, M; Hebbar, M; Ychou, M, 2009)	2.09
"Irinotecan has an anti-VEGF effect inhibiting endothelial cell proliferation, increasing apoptosis and reducing microvascular density which is only limited by irinotecan toxicity levels."	( Irinotecan therapy and molecular targets in colorectal cancer: a systemic review. Ho, YH; Lam, AK; Sebesan, S; Weekes, J, 2009)	2.52
"Irinotecan has radiosensitizing effects and shows synergism with nitrosoureas. "	( Phase II NCCTG trial of RT + irinotecan and adjuvant BCNU plus irinotecan for newly diagnosed GBM. Ames, MM; Arusell, R; Ballman, KV; Brown, PD; Buckner, JC; Galanis, E; Giannini, C; Hammack, JE; Jaeckle, KA; McGovern, RM; Morton, RF; Nikcevich, DA; Reid, JM; Safgren, SL; Schomberg, PJ; Uhm, JH; Wender, DB, 2010)	2.09
"Irinotecan (CPT-11) has shown emerging promise in the treatment of malignant gliomas. "	( Metronomic treatment of malignant glioma xenografts with irinotecan (CPT-11) inhibits angiogenesis and tumor growth. Ishikawa, E; Kamiyama, H; Mashiko, R; Matsumura, A; Osuka, S; Takano, S, 2010)	2.05
"Irinotecan has significant activity in small-cell lung cancer (SCLC). "	( Weekly alternating therapy with irinotecan plus cisplatin and etoposide plus cisplatin in the treatment of patients with extensive small cell lung carcinoma. Blumenschein, GR; Feng, L; Fossella, FV; Glisson, BS; Johnson, FM; Karp, DD; Peeples, BO; Stewart, DJ; Uyeki, J; William, WN, 2010)	2.09
"Irinotecan has an established role in the treatment of metastatic rectal cancer."	( Irinotecan and radiosensitization in rectal cancer. Illum, H, 2011)	2.53
"Irinotecan has a significant anti-tumour activity and acceptable toxicity in patients with relapsed hepatoblastoma and therefore should be considered for the treatment of these patients. "	( Efficacy of irinotecan single drug treatment in children with refractory or recurrent hepatoblastoma--a phase II trial of the childhood liver tumour strategy group (SIOPEL). Brock, P; Brugières, L; Casanova, M; Child, M; Czauderna, P; de Camargo, B; Maibach, R; Morland, B; Pariente, D; Paris, C; Perilongo, G; Plaschkes, J; Roebuck, D; Ronghe, M; Zimmermann, A; Zsíros, J, 2012)	2.2
"Irinotecan has been tested in various combinations with platinum agents but the optimal regimen remains uncertain."	( A phase I clinical trial of irinotecan and carboplatin in patients with extensive stage small cell lung cancer. Bradbury, J; Cave, J; Crabb, SJ; Johnson, PW; Muthuramalingam, SR; Nolan, L; Ottensmeier, C; Selman, D, 2012)	1.39
"Irinotecan has also been studied in combination regimens, most commonly irinotecan plus cisplatin."	( Irinotecan in epithelial ovarian cancer. Gershenson, DM, 2002)	2.48
"Irinotecan has shown antitumour activity in human testicular tumour xenografts in nude mice."	( Irinotecan in patients with relapsed or cisplatin-refractory germ cell cancer: a phase II study of the German Testicular Cancer Study Group. Bokemeyer, C; Hentrich, M; Kanz, L; Klaproth, H; Kollmannsberger, C; Kubin, T; Kuczyk, M; Mayer, F; Rick, O; Sayer, HG; Spott, C; Welslau, M, 2002)	2.48
"Irinotecan (CPT-11) has been shown to prolong survival and improve quality of life in comparison to best supportive care in colorectal cancer patients with pretreatment of bolus 5-fluorouracil (5-FU). "	( Adding weekly irinotecan to high-dose 5-fluorouracil and folinic acid (HD-5-FU/FA) after failure for first-line HD-5-FU/FA in advanced colorectal cancer--a phase II study. Emig, M; Hartung, G; Hehlmann, R; Hochhaus, A; Hofheinz, R; Pilz, L; Queisser, W; Samel, S; Willeke, F, 2002)	2.12
"Irinotecan has a reported response rate of 10%-20% in such patients."	( The palliative benefit of irinotecan in 5-fluorouracil-refractory colorectal cancer: its prospective evaluation by a Multicenter Canadian Trial. Feld, R; Fields, A; Goel, R; Hedley, D; Jolivet, J; Lee, IM; Maroun, J; Michael, M; Moore, MJ; Oza, A; Pintilie, M, 2002)	1.34
"Irinotecan has moderate efficacy and substantial toxicity in patients with metastatic platinum-resistant or platinum-refractory epithelial ovarian or primary peritoneal cancer."	( Phase II trial of irinotecan in patients with metastatic epithelial ovarian cancer or peritoneal cancer. Bodurka, DC; Gano, J; Gershenson, DM; Kavanagh, JJ; Levenback, C; Wharton, JT; Wolf, JK, 2003)	2.1
"Irinotecan has been widely used in the treatment of metastatic colorectal cancer, small cell lung cancer and several other solid tumors."	( Lessons learned from the irinotecan metabolic pathway. Ma, MK; McLeod, HL, 2003)	1.34
"Irinotecan (CPT11) has established activity against advanced colorectal cancer without cross-resistance with 5-fluorouracil + leucovorin-based therapy. "	( Irinotecan (CPT11) plus high-dose 5-fluorouracil (5-FU) and leucovorin (LV) as salvage therapy for metastatic colorectal cancer (MCRC) after failed oxaliplatin plus 5-FU and LV: a pilot study in Taiwan. Chen, PM; Chen, WS; Chiou, TJ; Lin, JK; Liu, JH; Tai, CJ; Wang, WS; Yen, CC, 2003)	3.2
"Irinotecan has shown activity in advanced colorectal cancer resistant to leucovorin and fluorouracil. "	( Bimonthly leucovorin, infusion 5-fluorouracil, hydroxyurea, and irinotecan (FOLFIRI-2) for pretreated metastatic colorectal cancer. André, T; Artru, P; Carola, E; de Gramont, A; Gilles-Amar, V; Krulik, M; Louvet, C; Mabro, M, 2003)	2
"Irinotecan hydrochloride has been administered to patients with breast cancer resistant to anthracyclines and/or taxanes in our department. "	( [Retrospective study on utility of irinotecan hydrochloride in patients with advanced and recurrent breast cancer]. Hirono, M; Ikeda, M; Kurebayashi, J; Nakashima, K; Nomura, N; Okubo, S; Sonoo, H; Tanaka, K; Udagawa, K; Yamamoto, Y, 2003)	2.04
"Irinotecan has proven anti-tumor activity as induction treatment in combination with 5-fluorouracil (5-FU) or as second-line treatment after 5-FU in patients with metastatic colorectal cancer. "	( Prospective multicenter phase II study of irinotecan as third-line therapy in metastatic colorectal cancer and progression after bolus and infusional 5-fluorouracil. Batran, SA; Bokemeyer, C; Büchele, T; Haag, C; Hartmann, JT; Hofheinz, RD; Jäger, E; Kanz, L; Niederle, N; Oechsle, K; Pflüger, KH; Reis, HE; Wilke, HJ, 2004)	2.03
"Irinotecan has been shown to exhibit excellent antitumor activity against SCLC in monotherapy regimens and in combination with cisplatin."	( Topoisomerase I inhibitors in small-cell lung cancer. The Japanese experience. Horiike, A; Saijo, N, 2004)	1.04
"Irinotecan (CPT-11) has been shown to exhibit excellent antitumour activity against small-cell lung cancer (SCLC). "	( Multi-institutional phase II trial of irinotecan, cisplatin, and etoposide for sensitive relapsed small-cell lung cancer. Goto, K; Kakinuma, R; Kodama, T; Kubota, K; Kunitoh, H; Matsui, K; Matsumoto, T; Niho, S; Nishiwaki, Y; Nokihara, H; Ohe, Y; Ohmatsu, H; Saijo, N; Sekine, I; Shinkai, T; Sugiura, T; Tamura, T; Yamamoto, N; Yoshida, K, 2004)	2.04
"Irinotecan (Camptosar) has shown promising single-agent activity in a number of gastrointestinal cancers, including colorectal, pancreatic, and esophagogastric cancer."	( Phase II trial of weekly irinotecan/cisplatin in advanced esophageal cancer. Ilson, DH, 2004)	1.35
"Irinotecan has many acute adverse effects."	( Benefit-risk assessment of irinotecan in advanced colorectal cancer. Glimelius, B, 2005)	1.35
"Irinotecan HCl (CPT-11) has frequently been used in chemotherapy or concurrent chemoradiotherapy for patients with advanced cervical cancer, although an effective protocol for chemoradiotherapy with CPT-11 has not yet been established. "	( Combination effects of irradiation and irinotecan on cervical squamous cell carcinoma cells in vitro. Tanaka, T; Umesaki, N; Yukawa, K, 2005)	2.04
"Irinotecan has recently been found to be one of the most active agents in the treatment of small-cell lung cancer (SCLC). "	( Evolving role of irinotecan in small-cell lung cancer. Greco, FA; Spigel, DR, 2003)	2.1
"Irinotecan has shown improved survival in patients who had previously failed 5-fluorouracil (5-FU)-based therapy in phase II and III trials."	( Second-line treatment of patients with metastatic colorectal cancer. Lepere, C; Rougier, P, 2005)	1.05
"Irinotecan has demonstrated broad activity in a variety of epithelial malignancies."	( A phase II trial of irinotecan in patients with previously untreated advanced esophageal and gastric adenocarcinoma. Clark, JW; Earle, CC; Enzinger, PC; Fuchs, CS; Kim, H; Kulke, MH; Mayer, RJ; Michelini, AL; Ryan, DP; Vincitore, MM, 2005)	1.37
"Irinotecan/cisplatin have been shown to be superior to a standard treatment with etoposide/cisplatin in extensive disease SCLC."	( Simultaneous chemoradiotherapy with irinotecan and cisplatin in limited disease small cell lung cancer: a phase I study. Büscher, C; Fähndrich, S; Fietkau, R; Klautke, G; Semrau, S; Virchow, C, 2006)	1.33
"Irinotecan has an acceptable tolerability profile and is not associated with cumulative toxicities in patients with metastatic CRC; regimens containing irinotecan extend treatment duration and improve survival."	( Irinotecan in the treatment of colorectal cancer. Fuchs, C; Hoff, PM; Mitchell, EP, 2006)	2.5
"Irinotecan (CPT-11) has been tested as a single agent in several studies, and response rates of 18-23% have been reported in first-line gastric cancer therapy. "	( Irinotecan, fluorouracil and folinic acid (FOLFIRI) as effective treatment combination for patients with advanced gastric cancer in poor clinical condition. Bajetta, E; Beretta, E; Buzzoni, R; Di Bartolomeo, M; Ferrario, E; Gevorgyan, A; Mariani, L, )	3.02
"Irinotecan (CPT11) has been evaluated in multiple trials alone or in combined therapy with promising results and good tolerance."	( A general review of the role of irinotecan (CPT11) in the treatment of gastric cancer. Farhat, FS, 2007)	1.34
"Irinotecan has been introduced to improve the treatment of small-cell lung cancer (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)	2.05
"Irinotecan has activity in the treatment of patients with metastatic colorectal cancer. "	( Irinotecan is an active agent in untreated patients with metastatic colorectal cancer. Chou, TC; Conti, JA; Gonzalez, C; Huang, Y; Kemeny, NE; Pulliam, S; Saltz, LB; Sun, M; Tong, WP, 1996)	3.18
"Irinotecan has significant single-agent activity against colorectal cancer that has progressed during or shortly after treatment with 5-FU-based chemotherapy. "	( Phase II trial of irinotecan in patients with progressive or rapidly recurrent colorectal cancer. Burris, HA; Eckardt, JR; Eckhardt, SG; Elfring, GL; Hilsenbeck, SG; Kuhn, JG; Nelson, J; Rinaldi, DA; Rodriguez, GI; Rothenberg, ML; Schaaf, LJ; Smith, LS; Thurman, AM; Von Hoff, DD; Weiss, GR, 1996)	2.07
"Irinotecan has established the single-agent efficacy on both gastric and colorectal cancer."	( New systemic drugs in the treatment of gastrointestinal cancer. Ogawa, M, 1996)	1.02
"Irinotecan (CPT-11) has been reported to be cytotoxic to tumor cells through its inhibitory activity on type I DNA topoisomerase. "	( Induction of tumor necrosis factor by a camptothecin derivative, irinotecan, in mice and human mononuclear cells. Goto, S; Kera, J; Okutomi, T; Soma, G; Suma, Y; Takeuchi, S, )	1.81
"Irinotecan has shown activity in leukaemia, lymphoma and the following cancer sites: colorectum, lung, ovary, cervix, pancreas, stomach and breast."	( Clinical pharmacokinetics of irinotecan. Chabot, GG, 1997)	1.31
"Irinotecan has significant activity in patients with 5-FU-refractory colorectal cancer. "	( Irinotecan hydrochloride: drug profile and nursing implications of a topoisomerase I inhibitor in patients with advanced colorectal cancer. Berg, D, 1998)	3.19
"Irinotecan has been approved in Japan, France and USA, however, its clinical usefulness seems to be differently understood. "	( [New cancer therapies: balancing risk and benefit]. Rothenberg, ML, 1998)	1.74
"Irinotecan has been explored as a single agent in patients with newly diagnosed CRC and has generated response rates in the range of 19% to 32% and a median survival time of approximately 12 months, suggesting a level of antitumor activity similar to that observed with 5-FU and leucovorin."	( Efficacy and toxicity of irinotecan in patients with colorectal cancer. Rothenberg, ML, 1998)	1.32
"Irinotecan only has been evaluated prospectively in phase III studies."	( [Second-line irinotecan chemotherapy in the treatment of metastatic colorectal cancers: phase III trials]. Ducreux, M; Mitry, E; Rougier, P, 1998)	1.39
"Irinotecan also has been used in combination with other chemotherapeutic agents."	( Docetaxel and irinotecan, alone and in combination, in the treatment of non-small cell lung cancer. Adjei, AA; Argiris, A; Murren, JR, 1999)	1.39
"Irinotecan has appeared to have significant activity against previously treated and untreated small-cell lung cancer (SCLC). "	( Irinotecan in small-cell lung cancer--Japanese trials. Fukuoka, M; Kudoh, S; Masuda, N; Negoro, S, 2000)	3.19
"Irinotecan (Camptosar) has shown activity in several solid tumor malignancies, including gastric and pancreatic cancer. "	( Irinotecan in esophageal cancer. Enzinger, PC; Ilson, DH, 2000)	3.19
"Irinotecan (CPT-11) has been used recently for the treatment of several cancers in combination with 5-fluorouracil (5-FU). "	( Comparisons of the pharmacokinetics and the leukopenia and thrombocytopenia grade after administration of irinotecan and 5-fluorouracil in combination to rats. Kiba, T; Nakaoka, M; Numata, K; Saito, T; Sekihara, H; Shintani, S; Umezawa, T, )	1.79
"Irinotecan (CPT11) has established activity in the treatment of advanced colorectal cancer without cross-resistance with established 5-fluorouracil/folinic acid-based therapy. "	( Prospective phase II trial of iriontecan, 5-fluorouracil, and leucovorin in combination as salvage therapy for advanced colorectal cancer. Adam, R; Bismuth, H; Castaing, D; Coeffic, D; Durrani, AK; Gil-Delgado, MA; Guinet, F; Khayat, D, 2001)	1.75
"Irinotecan (CPT-11) has shown considerable activity in colorectal cancer, and its combination with 5-fluorouracil (5-FU) represents an attractive approach. "	( A dose-finding study of irinotecan (CPT-11) plus a four-day continuous 5-fluorouracil infusion in advanced colorectal cancer. Androulakis, N; Georgoulias, V; Kakolyris, S; Kalbakis, K; Kotsakis, A; Koukourakis, M; Kouroussis, C; Mavroudis, D; Romanos, J; Souglakos, J; Vardakis, N, 2001)	2.06
"Irinotecan has not yet been fully tested in this disease."	( A phase II trial of irinotecan (CPT-11) for unresectable biliary tree carcinoma. Kemeny, NE; O'Reilly, E; Raeburn, L; Saltz, LB; Sanz-Altamira, PM; Steger, C; Stuart, KE, 2001)	1.36
"Irinotecan has minimal activity in biliary tree carcinomas, but is well tolerated with appropriate supportive care, and produces occasional objective responses."	( A phase II trial of irinotecan (CPT-11) for unresectable biliary tree carcinoma. Kemeny, NE; O'Reilly, E; Raeburn, L; Saltz, LB; Sanz-Altamira, PM; Steger, C; Stuart, KE, 2001)	2.08

Actions

Irinotecan can cause high levels of diarrhea caused by toxic injury to the gastrointestinal microenvironment. Irinotecen plays an important part in the treatment of metastatic colorectal cancer. It increases mucin secretion and a net decrease in mucin-producing goblet cells.

Excerpt	Reference	Relevance
"Irinotecan can cause high levels of diarrhea caused by toxic injury to the gastrointestinal microenvironment. "	( Intestinal toll-like receptor 4 knockout alters the functional capacity of the gut microbiome following irinotecan treatment. Bowen, JM; Coller, JK; Crame, EE; Gibson, RJ; Secombe, KR; Tam, JSY; Wardill, HR, 2022)	2.38
"Irinotecan did not increase the number of TUNEL-positive cells and did not affect the population of propidium iodide (PI)-positive and annexin V-negative cells, corresponding to primary necrosis, or that of PI-positive and annexin-positive cells, corresponding to late apoptosis/secondary necrosis, in either of the two cell lines."	( Irinotecan induces cell cycle arrest, but not apoptosis or necrosis, in Caco-2 and CW2 colorectal cancer cell lines. Kaku, Y; Kanno, T; Nishizaki, T; Tsuchiya, A, 2015)	2.58
"Irinotecan causes an increase in mucin secretion and a net decrease in mucin-producing goblet cells, and the expression of Muc2 and Muc4 in the gastrointestinal tract is altered following treatment. "	( Irinotecan-induced mucositis is associated with changes in intestinal mucins. Bowen, JM; Gibson, RJ; Keefe, DM; Laurence, J; Logan, RM; Stringer, AM; Yeoh, AS, 2009)	3.24
"Irinotecan plays now an important part in the treatment of metastatic colorectal cancer."	( [Irinotecan in combination for colon cancer]. André, T; de Gramond, A; Ducreux, M; Gil-Delgado, M; Khayat, D; Ychou, M, 1998)	1.93

Treatment

Irinotecan treatment was highly effective in a preclinical model of human MTC, resulting in complete remission in 100% of the xenografts treated. IrinOTecan-treated patients had significantly prolonged survival, improved quality of life, and better control of disease-related symptoms.

Excerpt	Reference	Relevance
"In irinotecan-treated rats, ∼2-fold increases in Pept1 protein levels were observed in all three segments, whereas mRNA levels remained unchanged."	( Irinotecan-induced gastrointestinal damage alters the expression of peptide transporter 1 and absorption of cephalexin in rats. Akiyoshi, T; Hattori, T; Imaoka, A; Ohtani, H, 2023)	2.87
"The irinotecan-treated group showed statistically significant shortening and thinning of the lingual papillae."	( Effect of irinotecan on the tongue mucosa of juvenile male albino rat at adulthood. Elwan, WM; Ibrahim, MAAH, 2019)	1.4
"Irinotecan treats a range of solid tumors, but its effectiveness is severely limited by gastrointestinal (GI) tract toxicity caused by gut bacterial β-glucuronidase (GUS) enzymes. "	( Targeted inhibition of gut bacterial β-glucuronidase activity enhances anticancer drug efficacy. Azcarate-Peril, MA; Bailey, ST; Bhatt, AP; Biernat, KA; Bultman, SJ; Creekmore, BC; Darr, DB; Gharaibeh, RZ; Letertre, MM; Montgomery, SA; Pellock, SJ; Redinbo, MR; Roach, JM; Roques, JR; Sartor, RB; Swann, JR; Wallace, BD; Walton, WG; Wilson, ID, 2020)	2
"In irinotecan-treated patients, T allele of ABCB1C1236T SNP was associated with a lower risk of asthenia(OR = 0.047; 95 % CI = 0.004–0.493; P = 0.011) and Tallele of ABCB1 C3435T SNP was associated with a lower risk of diarrhea (OR = 0.177; 95 % CI = 0.034–0.919;P = 0.039), and individuals with two copies of GSTT1 gene had a lower risk for asthenia (OR = 0.093; 95 %CI = 0.011–0.794; P = 0.030). "	( 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)	1.28
"Irinotecan treatment is associated with mucositis, which clearly limits the use of the drug."	( Inflammasome activation is reactive oxygen species dependent and mediates irinotecan-induced mucositis through IL-1β and IL-18 in mice. Arifa, RD; de Paula, TP; Fagundes, CT; Lima, RL; Madeira, MF; Menezes-Garcia, Z; Rachid, MA; Ryffel, B; Souza, DG; Tavares, LD; Teixeira, MM; Zamboni, DS, 2014)	1.35
"Irinotecan, a first-line treatment for metastatic colorectal cancer and an agent with high activity against solid tumors of the gastrointestinal tract, is an inhibitor of topoisomerase I, a critical enzyme needed for DNA transcription."	( Experience with irinotecan for the treatment of malignant glioma. Desjardins, A; Friedman, HS; Reardon, DA; Vredenburgh, JJ, 2009)	1.42
"Irinotecan (CPT11) treatment significantly improves the survival of colorectal cancer patients and is routinely used for the treatment of these patients, alone or in combination with other agents. "	( Aprataxin tumor levels predict response of colorectal cancer patients to irinotecan-based treatment. Arango, D; Armengol, M; Bazzocco, S; Carreras, MJ; Dopeso, H; Elez, E; Espín, E; Hernández-Losa, J; Landolfi, S; Mariadason, JM; Mateo-Lozano, S; Mazzolini, R; Ramon Y Cajal, S; Ramos Pascual, FJ; Rodrigues, P; Schwartz, S; Tabernero, J; Wilson, AJ, 2010)	2.03
"Irinotecan-treated patients were genotyped for the MBL2 gene. "	( Effects of mannose-binding lectin polymorphisms on irinotecan-induced febrile neutropenia. de Jong, FA; Mathijssen, RH; Sleijfer, S; Sparreboom, A; van Daele, PL; van de Geijn, FE; van der Bol, JM; van Fessem, MA; van Schaik, RH; Verweij, J, 2010)	2.06
"Irinotecan treated rats were administrated irinotecan 250 mg/kg intraperitoneally on days designated 0 and 1, were then killed at 48 h after treatment, and tissues were collected for analysis."	( Irinotecan injures tight junction and causes bacterial translocation in rat. Iwata, T; Komatsu, M; Kurita, N; Nakao, T; Shimada, M; Utusnomiya, T; Yoshikawa, K, 2012)	2.54
"In irinotecan treated rats, claudin-1 mRNA of the small intestine decreased (P < 0.05), claudin-1 mRNA of large intestine had a tendency to decrease (P = 0.05), occludin mRNA of both small and large intestine decreased (P < 0.05)."	( Irinotecan injures tight junction and causes bacterial translocation in rat. Iwata, T; Komatsu, M; Kurita, N; Nakao, T; Shimada, M; Utusnomiya, T; Yoshikawa, K, 2012)	2.34
"Irinotecan, now used for treatments of many cancers, is metabolically activated to SN-38 and then inactivated to SN-38 glucuronide by a UDP-glucuronosyltransferase UGT1A1."	( [Pharmacogenomic research for avoiding adverse reactions by anti-cancer drugs]. Saito, Y, 2011)	1.09
"Irinotecan treatment resulted in a suppression of tumor growth. "	( Pharmacodynamic evaluation of irinotecan therapy by FDG and FLT PET/CT imaging in a colorectal cancer xenograft model. Bukofzer, G; Chakravartty, A; Cole, TB; Day, M; Donawho, CK; Fox, GB; Holich, KD; Luo, Y; Mudd, SR; Palma, JP; Reuter, DR; Tapang, P; Voorbach, MJ, 2012)	2.11
"Irinotecan (CPT-11) treatments induce severe diarrhoea at a rate of >40%. "	( Prevention of irinotecan-induced diarrhoea by oral carbonaceous adsorbent (Kremezin) in cancer patients. Kiribayashi, Y; Maeda, Y; Murakami, T; Nakamura, M; Ohune, T; Yamasaki, M, 2004)	2.13
"Irinotecan-treated patients received a mean of 8 different comedications and oxaliplatin-treated patients received a mean of 6."	( 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)	1.28
"Irinotecan treatment also induced in mouse tumours derived from the p53(wt) cell lines a tetraploid G1 arrest and in those derived from the p53-deficient cell lines a transient G2/M arrest and apoptosis."	( Equivalent effect of DNA damage-induced apoptotic cell death or long-term cell cycle arrest on colon carcinoma cell proliferation and tumour growth. Bhonde, MR; Daniel, PT; Gillissen, BF; Hanski, C; Hanski, ML; Notter, M; Zeitz, M, 2006)	1.06
"Irinotecan treatment was highly effective in a preclinical model of human MTC, resulting in complete remission in 100% of the xenografts treated. "	( Activity of irinotecan and the tyrosine kinase inhibitor CEP-751 in medullary thyroid cancer. Ball, DW; Denmeade, SR; Nelkin, BD; Park, JI; Rosen, DM; Ruggeri, B; Strock, CJ, 2006)	2.16
"Irinotecan treatment of colorectal cancers results in high-grade intestinal mucositis in a large proportion of patients. "	( Role of p53 in irinotecan-induced intestinal cell death and mucosal damage. Bowen, JM; Chan, TW; Cummins, AG; Gibson, RJ; Keefe, DM; Prabowo, AS; Stringer, AM, 2007)	2.14
"Irinotecan-treated patients had significantly prolonged survival, improved quality of life, and better control of disease-related symptoms."	( Irinotecan: toward clinical end points in drug development. Pazdur, R, 1998)	2.46
"Irinotecan treated patients lived for significantly longer than those on 5FU: median time of survival was 10.8 months versus 8.5 months (p = 0.035)."	( [Second-line irinotecan chemotherapy in the treatment of metastatic colorectal cancers: phase III trials]. Ducreux, M; Mitry, E; Rougier, P, 1998)	1.39
"Irinotecan treatment was repeated in approximately 6 week cycles consisting of the administration of irinotecan once weekly for 4 weeks followed by a 2 week rest."	( Clinical effect of irinotecan in advanced and metastatic breast cancer patients previously treated with doxorubicin- and docetaxel-containing regimens. Fujii, H; Igarashi, T; Imoto, S; Ishizawa, K; Itoh, K; Minami, H; Saeki, T; Sasaki, Y; Shigeoka, Y, 2001)	1.36
"Treatment with irinotecan significantly inhibited cell proliferation and induced cell apoptosis, TRIM9 expression, intestinal mucosal barrier impairment, the levels of inflammatory cytokines and P38 phosphorylation in IEC‑6 cells, while the expression levels of epithelial barrier tight‑junction protein ZO‑1 and Claudin‑4 were decreased."	( Knockdown of TRIM9 attenuates irinotecan‑induced intestinal mucositis in IEC‑6 cells by regulating DUSP6 expression via the P38 pathway. Wang, Q; Zhao, W, 2021)	1.25
"Co-treatment with irinotecan and ATP-competitive AKT inhibitor GSK690693 significantly reduced colon cancer cell survival and tumor progression rates."	( AKT inhibition sensitizes EVI1 expressing colon cancer cells to irinotecan therapy by regulating the Akt/mTOR axis. Chakraborty, S; Senapati, S; Suresh, V, 2022)	1.28
"The treatment of irinotecan with combining ellagic acid enhanced antitumor activity and the synergistic effect of these reduced the cell proliferation of C6 glioma by inhibiting the cadherin switch and promoting the antiangiogenic processes."	( Antitumor activity of irinotecan with ellagic acid in C6 glioma cells. Biltekin, B; Cetin, A; Ozevren, H, 2022)	1.38
"Treatment with irinotecan or oxaliplatin in combination with 5-FU inhibited proliferation and metabolic activity as well as clonogenic survival and the DNA damage repair capacity of the tumor cells."	( 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)	1.54
"Treatment with irinotecan is often accompanied by severe toxicity (e.g."	( Irinotecan toxicity during treatment of metastatic colorectal cancer: focus on pharmacogenomics and personalized medicine. Filip, S; Nekvindová, J; Paulík, A, 2020)	2.34
"Treatment with irinotecan or etoposide did not significantly influence cellular adhesion, migratory ability, surface marker expression or induction of apoptosis in human MSCs."	( Mesenchymal stem cells exhibit resistance to topoisomerase inhibition. Debus, J; Ho, AD; Huber, PE; Nicolay, NH; Perez, RL; Rühle, A; Saffrich, R; Schmezer, P; Sisombath, S; Trinh, T; Weber, KJ, 2016)	0.77
"Mice treated with Irinotecan presented less melanoma tumor growth compared to the control group."	( The reduction of oxidative stress by nanocomposite Fullerol decreases mucositis severity and reverts leukopenia induced by Irinotecan. Arifa, RDN; Barcelos, LS; Garcia, ZM; Krambrock, K; Ladeira, LO; Lima, RL; Madeira, MFM; Paula, TP; Pinheiro, MVB; Pinho, V; Souza, DG; Teixeira, MM; Ÿvila, TV, 2016)	0.96
"Treatment with irinotecan was significantly associated with an increase in the incidence of steatohepatitis, but did not increase the morbidity or mortality. "	( [Influence of pre-surgical chemotherapy on liver parenchyma and post-surgical outcome of patients subjected to hepatectomy due to colorectal carcinoma metastases]. Amat, CG; Bermejo, E; Gómez-Ramírez, J; Larrañaga, E; Martín-Pérez, E; Rodríguez, A; Sanz, IG, 2010)	0.71
"Treatment was irinotecan 350 mg/m2, i.v., day 1, alternating with leucovorin 20 mg/m2 i.v."	( A phase II study of irinotecan alternated with five days bolus of 5-fluorouracil and leucovorin in first-line chemotherapy of metastatic colorectal cancer. Barone, C; Cognetti, F; Cote, C; Dirix, L; Filez, L; Garufi, C; Gruia, G; Humblet, Y; Pozzo, C; Starkhammar, H; Terzoli, E; Van Cutsem, E, 1998)	0.97

Toxicity

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. The majority of the toxic manifestation is caused by the insufficient deactivation (glucuronidation) of the irinOTecan active metabolite SN-38 by UGT1A enzyme.

Excerpt	Reference	Relevance
" 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
" 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)	0.54
" 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)	0.78
" 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
" 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)	0.76
" 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)	1.98
" 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)	0.59
" 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)	0.59
" 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
"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)	0.76
" 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)	0.56
" 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)	0.55
"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)	2.05
" 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, )	0.39
" 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)	0.88
" 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)	0.69
"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)	0.94
"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)	0.71
" 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)	0.54
" 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)	0.54
"5 million adverse drug reaction (ADR) reports for 8620 drugs/biologics that are listed for 1191 Coding Symbols for Thesaurus of Adverse Reaction (COSTAR) terms of adverse effects."	( Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling. Benz, RD; Contrera, JF; Kruhlak, NL; Matthews, EJ; Weaver, JL, 2004)	0.32
"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)	0.84
"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)	0.54
" 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)	0.55
" 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)	1.99
"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)	0.55
" 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)	0.6
" 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)	0.93
" 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)	0.74
" 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)	0.56
"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)	0.92
" 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)	0.56
"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)	0.88
"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)	0.66
"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)	0.75
" 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)	0.59
" 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)	2.13
"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)	0.56
"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, )	0.38
" 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
"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)	0.56
" 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)	0.62
" 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)	0.58
" 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)	0.78
" 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)	0.59
"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)	0.99
"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)	0.87
" 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
" 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)	1.02
"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)	0.74
" 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
" 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)	0.73
" 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)	0.61
" 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)	0.9
" 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)	0.59
" 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)	0.59
"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)	0.84
" 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
"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
"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)	0.67
" 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)	0.59
" 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)	0.6
" 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)	0.76
"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)	0.76
"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)	0.8
" 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)	0.6
" 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)	0.6
" 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)	0.66
" 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)	0.95
"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)	0.8
"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)	0.82
" 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)	1.04
"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)	0.67
" 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)	0.83
" 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
"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)	0.65
" 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)	0.6
" 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)	0.65
"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
"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)	0.63
" 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)	0.4
" 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)	0.88
" 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)	0.71
" 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)	0.71
"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)	0.93
"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)	0.86
"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)	0.82
" 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)	0.89
"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)	2.06
"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)	0.91
"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
" 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)	0.69
" 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)	0.69
"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)	0.68
" 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)	0.64
" 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)	0.9
" 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)	0.67
" 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)	2.13
" 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)	0.65
" 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)	0.66
"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
" 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)	0.86
"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)	0.94
" 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)	0.74
"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)	0.68
" 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
" 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
" 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
" Polymorphisms rs8175347, rs17868323, rs3832043, rs11692021 and rs7577677 were associated with a higher incidence of adverse effects."	( Effect of UGT, SLCO, ABCB and ABCC polymorphisms on irinotecan toxicity. García Gil, S; Gutiérrez Nicolás, F; Llanos Muñoz, M; Martín Calero, B; Nazco Casariego, GJ; Pérez Pérez, JA; Ramos Díaz, R; Viña Romero, MM, 2018)	0.73
" Bevacizumab was administered at a dose of 100 mg intravenously once a week combined with one or two types of chemotherapeutic drugs until confirmed disease progression or an intolerable adverse event was observed."	( Analysis of the activity and safety of weekly low-dose bevacizumab-based regimens in heavily pretreated patients with metastatic breast cancer. Chen, J; Fan, Y; Hong, R; Ma, F; Ou, K; Sang, D; Wang, J; Xu, B; Yuan, P; Zhai, X; Zhao, C, 2018)	0.48
" The most common hematological adverse events were neutropenia, anemia, and thrombocytopenia."	( Analysis of the activity and safety of weekly low-dose bevacizumab-based regimens in heavily pretreated patients with metastatic breast cancer. Chen, J; Fan, Y; Hong, R; Ma, F; Ou, K; Sang, D; Wang, J; Xu, B; Yuan, P; Zhai, X; Zhao, C, 2018)	0.48
" The objective of this study was to compare outcome measures, adverse effects, and cost of FOLFOX4 and FOLFIRINOX treatments in rectal cancer patients."	( Comparisons of Efficacy, Safety, and Cost of Chemotherapy Regimens FOLFOX4 and FOLFIRINOX in Rectal Cancer: A Randomized, Multicenter Study. Chen, Y; Liu, J; Qi, F; Yan, Q; Zhang, G; Zheng, Z, 2018)	0.48
"FOLFIRINOX has been one of the first-line options for advanced pancreatic cancer, even though it induces significant adverse effects."	( The benefits of modified FOLFIRINOX for advanced pancreatic cancer and its induced adverse events: a systematic review and meta-analysis. Fan, Z; Liu, B; Lu, T; Tong, H, 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)	1.01
" Toxic and therapeutic effects of IRI are also due to its active metabolite SN-38, reported to be up to 100 times more cytotoxic than IRI."	( Pharmacokinetic and Pharmacogenetic Markers of Irinotecan Toxicity. Antunes, MV; Hahn, RZ; Linden, R; Perassolo, MS; Schwartsmann, G; Suyenaga, ES; Verza, SG, 2019)	0.77
" 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)	0.72
" 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)	0.72
" The most common grade 3/4 adverse events were neutropenia (13 patients, 18%), febrile neutropenia (3 patients, 4%), diarrhea (11 patients, 15%), hypertension (19 patients, 26%), proteinuria (8 patients, 11%), infections (8 patients, 11%), and mucositis (6 patients, 8%), with no toxic deaths."	( AMALTHEA: Prospective, Single-Arm Study of the Hellenic Cooperative Oncology Group (HeCOG) Evaluating Efficacy and Safety of First-Line FOLFIRI + Aflibercept for 6 Months Followed by Aflibercept Maintenance in Patients With Metastatic Colorectal Cancer. Aravantinos, G; Bafaloukos, D; Efstratiou, I; Fountzilas, G; Goudopoulou, A; Kalogera-Fountzila, A; Kalogeropoulou, L; Karavasilis, V; Kentepozidis, N; Koliou, GA; Kotoula, V; Koumakis, G; Laschos, K; Pectasides, D; Pentheroudakis, G; Petraki, C; Poulios, C; Samantas, E; Sgouros, J; Souglakos, I; Tikas, I; Voutsina, A; Vrettou, E; Zarkavelis, G, 2018)	0.48
" Preliminary data hint that this regimen has cytoreductive activity in disease with adverse biology."	( AMALTHEA: Prospective, Single-Arm Study of the Hellenic Cooperative Oncology Group (HeCOG) Evaluating Efficacy and Safety of First-Line FOLFIRI + Aflibercept for 6 Months Followed by Aflibercept Maintenance in Patients With Metastatic Colorectal Cancer. Aravantinos, G; Bafaloukos, D; Efstratiou, I; Fountzilas, G; Goudopoulou, A; Kalogera-Fountzila, A; Kalogeropoulou, L; Karavasilis, V; Kentepozidis, N; Koliou, GA; Kotoula, V; Koumakis, G; Laschos, K; Pectasides, D; Pentheroudakis, G; Petraki, C; Poulios, C; Samantas, E; Sgouros, J; Souglakos, I; Tikas, I; Voutsina, A; Vrettou, E; Zarkavelis, G, 2018)	0.48
"Preventing severe irinotecan-induced adverse reactions would allow us to offer better treatment and improve patients' quality of life."	( Clinical utility of ABCB1 genotyping for preventing toxicity in treatment with irinotecan. Blanco, C; García, MI; García-Alfonso, P; García-González, X; Grávalos, C; Longo, F; López-Fernández, LA; Martínez, V; Pachón, V; Robles, L; Salvador-Martín, S; Sanjurjo-Sáez, M, 2018)	1.04
" However, there are serious adverse events associated with its use, especially severe hypertension and gastrointestinal perforation, that need to be considered."	( Comparative Effectiveness and Safety of Monoclonal Antibodies (Bevacizumab, Cetuximab, and Panitumumab) in Combination with Chemotherapy for Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis. Almeida, PHRF; Andrade, EIG; Cherchiglia, ML; da Silva, WC; de Araujo, VE; de Assis Acurcio, F; Dos Santos, JBR; Godman, B; Kurdi, A; Lima, EMEA; Silva, MRRD, 2018)	0.48
" It can cause severe adverse drug reactions, such as neutropenia or diarrhea."	( The risk of adverse events of CPT- 11. Ichikawa, W; Imataka, H; Sekikawa, T, 2016)	0.43
" No statistical differences were observed in treatment-related adverse events, hospital admissions, or further treatment lines between age groups."	( Second-line treatment efficacy and toxicity in older vs. non-older patients with advanced gastric cancer: A multicentre real-world study. Antonuzzo, L; Aprile, G; Avallone, A; Bordonaro, R; Cinieri, S; Di Donato, S; Fanotto, V; Fornaro, L; Gerratana, L; Giampieri, R; Leone, F; Melisi, D; Nichetti, F; Pellegrino, A; Rimassa, L; Rosati, G; Santini, D; Scartozzi, M; Silvestris, N; Stragliotto, S; Tomasello, G; Vasile, E, 2019)	0.51
" Incidence of adverse events was similar between age groups."	( Second-line treatment efficacy and toxicity in older vs. non-older patients with advanced gastric cancer: A multicentre real-world study. Antonuzzo, L; Aprile, G; Avallone, A; Bordonaro, R; Cinieri, S; Di Donato, S; Fanotto, V; Fornaro, L; Gerratana, L; Giampieri, R; Leone, F; Melisi, D; Nichetti, F; Pellegrino, A; Rimassa, L; Rosati, G; Santini, D; Scartozzi, M; Silvestris, N; Stragliotto, S; Tomasello, G; Vasile, E, 2019)	0.51
" Grade 3 or higher adverse events of special interest were neutropenia (13%, 22%, and 64% for the WT, SH and Homo/DH genotypes), febrile neutropenia (2%, 7%, and 50%) and diarrhea (6%, 5%, and 21%)."	( Association between UGT1A1 gene polymorphism and safety and efficacy of irinotecan monotherapy as the third-line treatment for advanced gastric cancer. Boku, N; Hamaguchi, T; Higuchi, K; Honma, Y; Iwasa, S; Kato, K; Shoji, H; Takashima, A; Yamaguchi, T, 2019)	0.75
" Catheter-related adverse events were reported per Society of Interventional Radiology classification, and treatment toxicities were reported per Common Terminology Criteria for Adverse Events."	( Feasibility and Safety of CT-Guided High-Dose-Rate Brachytherapy Combined with Transarterial Chemoembolization Using Irinotecan-Loaded Microspheres for the Treatment of Large, Unresectable Colorectal Liver Metastases. Collettini, F; Gebauer, B; Geisel, D; Jonczyk, M; Meddeb, A; Schnapauff, D; Wieners, G, 2020)	0.77
"Combined irinotecan chemoembolization and CT-guided HDRBT is safe and shows a low incidence of toxicities, which were self-resolving."	( Feasibility and Safety of CT-Guided High-Dose-Rate Brachytherapy Combined with Transarterial Chemoembolization Using Irinotecan-Loaded Microspheres for the Treatment of Large, Unresectable Colorectal Liver Metastases. Collettini, F; Gebauer, B; Geisel, D; Jonczyk, M; Meddeb, A; Schnapauff, D; Wieners, G, 2020)	1.18
" Anti-EGFR MoAbs have increased the risk of adverse effects than chemotherapy alone."	( Efficacy and safety of anti-EGFR monoclonal antibodies combined with different chemotherapy regimens in patients with RAS wild-type metastatic colorectal cancer: A meta-analysis. Han, J; Li, J; Li, Y; Su, Y; Sun, H; Wu, X; Zhou, X, 2019)	0.51
"Gastrointestinal (GI)-related adverse events (AEs) are commonly observed in the clinic during cancer treatments."	( A Citrulline-Based Translational Population System Toxicology Model for Gastrointestinal-Related Adverse Events Associated With Anticancer Treatments. Abdul-Hadi, K; Brown, A; Guan, E; Wagoner, M; Yoneyama, T; Zhu, AZX, 2019)	0.51
" Here, we discover the specific bacterial GUS enzymes that generate SN-38, the active and toxic metabolite of irinotecan, from human fecal samples using a unique activity-based protein profiling (ABPP) platform."	( Discovering the Microbial Enzymes Driving Drug Toxicity with Activity-Based Protein Profiling. Artola, M; Bhatt, AP; Cloer, EW; Davies, GJ; Goldfarb, D; Jariwala, PB; Major, MB; Overkleeft, HS; Pellock, SJ; Redinbo, MR; Roberts, LR; Simpson, JB; Walton, WG, 2020)	0.77
" However, their use in the elderly is discouraged because of adverse events."	( The efficacy and toxicity of chemotherapy in the elderly with advanced pancreatic cancer. Bai, XL; Chen, W; Chen, YW; Fu, QH; Gao, SL; Guo, CX; Huang, DB; Li, X; Liang, TB; Ma, T; Que, RS; Su, W; Tang, TY; Zhang, Q; Zhang, XC, 2020)	0.56
" The objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), overall survival (OS) and adverse events were compared between the groups."	( The efficacy and toxicity of chemotherapy in the elderly with advanced pancreatic cancer. Bai, XL; Chen, W; Chen, YW; Fu, QH; Gao, SL; Guo, CX; Huang, DB; Li, X; Liang, TB; Ma, T; Que, RS; Su, W; Tang, TY; Zhang, Q; Zhang, XC, 2020)	0.56
" However, the elderly patients suffered a higher incidence of severe adverse events (50% vs."	( The efficacy and toxicity of chemotherapy in the elderly with advanced pancreatic cancer. Bai, XL; Chen, W; Chen, YW; Fu, QH; Gao, SL; Guo, CX; Huang, DB; Li, X; Liang, TB; Ma, T; Que, RS; Su, W; Tang, TY; Zhang, Q; Zhang, XC, 2020)	0.56
"Delayed diarrhea is a common side effect of irinotecan administration, leading to a reduction in dose and thus a delay in anticancer therapy."	( Ganciclovir reduces irinotecan-induced intestinal toxicity by inhibiting NLRP3 activation. Huang, H; Jiang, W; Jinbo, M; Wang, H; Wang, X; Yu, P; Zhang, G; Zhang, X, 2020)	1.14
" In stage two, an additional 20 patients were enrolled at a starting dose as defined in stage one, provided that in stage ≥1 objective response or ≥2 stable diseases were observed and ≤3 patients had serious adverse events (SAEs) within the first 6 weeks of treatment."	( Efficacy and safety of FOLFIRINOX as salvage treatment in advanced biliary tract cancer: an open-label, single arm, phase 2 trial. Belkouz, A; de Vos-Geelen, J; Eskens, FALM; Klümpen, HJ; Mathôt, RAA; Punt, CJA; van Gulik, TM; van Oijen, MGH; Wilmink, JW, 2020)	0.56
" One patient had a SAE during the first 6 weeks of treatment, and five patients required a dose reduction due to adverse events."	( Efficacy and safety of FOLFIRINOX as salvage treatment in advanced biliary tract cancer: an open-label, single arm, phase 2 trial. Belkouz, A; de Vos-Geelen, J; Eskens, FALM; Klümpen, HJ; Mathôt, RAA; Punt, CJA; van Gulik, TM; van Oijen, MGH; Wilmink, JW, 2020)	0.56
"Diarrhea is a common adverse reaction in patients with cancer receiving chemotherapy, for which there is currently no effective method of treatment."	( Efficacy and safety of Shengjiang Xiexin decoction in prophylaxis of chemotherapy-related diarrhea in small cell lung cancer patients: study protocol for a multicenter randomized controlled trial. Deng, B; Deng, C; Gao, Y; Jia, L; Lou, Y; Su, F, 2020)	0.56
"9 months, respectively; gastrointestinal dysfunction, leukopenia and hypertension were the three most common adverse events, accounting for 36."	( Therapeutic effect and side effects of Bevacizumab combined with Irinotecan in the treatment of paediatric intracranial tumours: Meta-analysis and Systematic Review. Di, F; Li, Q; Ma, HY; Sun, T; Xiang, RL; Xu, Y, 2020)	0.8
" Gastrointestinal dysfunction, leukopenia and hypertension were the toxic side effects with the highest incidence."	( Therapeutic effect and side effects of Bevacizumab combined with Irinotecan in the treatment of paediatric intracranial tumours: Meta-analysis and Systematic Review. Di, F; Li, Q; Ma, HY; Sun, T; Xiang, RL; Xu, Y, 2020)	0.8
" No toxic death was observed."	( Safety and Efficacy of Gemcitabine, Docetaxel, Capecitabine, Cisplatin as Second-line Therapy for Advanced Pancreatic Cancer After FOLFIRINOX. Bengrine, L; Fumet, JD; Ghiringhelli, F; Granconato, L; Hennequin, A; Palmier, R; Vincent, J, 2020)	0.56
" Gastrointestinal mucositis is a common and debilitating side-effect of anticancer therapy contributing to dose reductions, delays and cessation of treatment, greatly impacting clinical outcomes."	( Impact of chemotherapy-induced enteric nervous system toxicity on gastrointestinal mucositis. Al Thaalibi, M; McQuade, RM; Nurgali, K, 2020)	0.56
" Adverse events during the first 30 days upon initial treatment were hypertension in 21."	( LifePearl microspheres loaded with irinotecan in the treatment of Liver-dominant metastatic colorectal carcinoma: feasibility, safety and pharmacokinetic study. Helmberger, T; Isailovic, TV; Maleux, G; Pereira, P; Prenen, H; Spriet, I, 2020)	0.84
"Current adverse event reporting practices do not document longitudinal characteristics of adverse effects, and alternative methods are not easily interpretable and have not been employed by clinical trials."	( Adverse event load, onset, and maximum grade: A novel method of reporting adverse events in cancer clinical trials. Cohen, R; de Gramont, A; Fuchs, C; Goldberg, RM; Hurwitz, H; Kempf, E; Lopes, GS; Olswold, CL; Saltz, L; Shi, Q; Tournigand, C, 2021)	0.62
"Our method provided additional information compared to traditional adverse event reports."	( Adverse event load, onset, and maximum grade: A novel method of reporting adverse events in cancer clinical trials. Cohen, R; de Gramont, A; Fuchs, C; Goldberg, RM; Hurwitz, H; Kempf, E; Lopes, GS; Olswold, CL; Saltz, L; Shi, Q; Tournigand, C, 2021)	0.62
"We developed an adverse event reporting method that provides clinically relevant information about treatment toxicity by incorporating two longitudinal adverse event metrics to the traditional maximum grade approach."	( Adverse event load, onset, and maximum grade: A novel method of reporting adverse events in cancer clinical trials. Cohen, R; de Gramont, A; Fuchs, C; Goldberg, RM; Hurwitz, H; Kempf, E; Lopes, GS; Olswold, CL; Saltz, L; Shi, Q; Tournigand, C, 2021)	0.62
" The main toxic side effect of the patients was gastrointestinal reaction in both groups."	( The efficacy and safety of irinotecan combined with nedaplatin in the treatment of small cell lung cancer. Fang, S; Fu, J; Wang, D; Wang, Y; Wen, Y; Yin, X, )	0.43
" The outcomes were overall response rate, overall survival, progression-free survival, and the incidence of the most common adverse events."	( Efficacy and Safety of Bevacizumab Plus Oxaliplatin- or Irinotecan-Based Doublet Backbone Chemotherapy as the First-Line Treatment of Metastatic Colorectal Cancer: A Systematic Review and Meta-analysis. Hui, F; Qi, X; Ren, T; Shen, Z; Wang, S; Xu, C; Zhang, Y; Zhao, Q, 2021)	0.87
" The two different doublet regimens combined with BEV had their specific features of adverse events."	( Efficacy and Safety of Bevacizumab Plus Oxaliplatin- or Irinotecan-Based Doublet Backbone Chemotherapy as the First-Line Treatment of Metastatic Colorectal Cancer: A Systematic Review and Meta-analysis. Hui, F; Qi, X; Ren, T; Shen, Z; Wang, S; Xu, C; Zhang, Y; Zhao, Q, 2021)	0.87
"A monocentric comparative before/after study was carried out in an oncology day hospital to evaluate the efficacy of Safe Infusion Devices in reducing drug exposure compared to usual infusion practices."	( Evaluation of a safe infusion device on reducing occupational exposure of nurses to antineoplastic drugs: a comparative prospective study. Contamoins-1. Blanc, E; Bouleftour, W; Forges, F; Guitton, J; Hugues, M; Macé, A; Macron, C; Menguy, S; Raymond, B; Simoëns, X; Tinquaut, F, 2021)	0.62
"3% of contaminated samples while Safe Infusion Devices to a rate of 15%: Safe Infusion Devices reduced the risk of gloves contamination by 85% in multivariate analysis (Odds ratio = 0."	( Evaluation of a safe infusion device on reducing occupational exposure of nurses to antineoplastic drugs: a comparative prospective study. Contamoins-1. Blanc, E; Bouleftour, W; Forges, F; Guitton, J; Hugues, M; Macé, A; Macron, C; Menguy, S; Raymond, B; Simoëns, X; Tinquaut, F, 2021)	0.62
"Despite the current practice of using neutral solvent-purged infusers, the occupational exposure remains high for nurses and Safe Infusion Devices significantly reduced this risk of exposure."	( Evaluation of a safe infusion device on reducing occupational exposure of nurses to antineoplastic drugs: a comparative prospective study. Contamoins-1. Blanc, E; Bouleftour, W; Forges, F; Guitton, J; Hugues, M; Macé, A; Macron, C; Menguy, S; Raymond, B; Simoëns, X; Tinquaut, F, 2021)	0.62
"Genetic variations of enzymes that affect the pharmacokinetics and hence effects of medications differ between ethnicities, resulting in variation in the risk of adverse drug reactions (ADR) between different populations."	( The Use of Subgroup Disproportionality Analyses to Explore the Sensitivity of a Global Database of Individual Case Safety Reports to Known Pharmacogenomic Risk Variants Common in Japan. Aoki, Y; Chandler, RE; Lönnstedt, IM; Wakao, R, 2021)	0.62
"Callispheres® microspheres (CSM) are the first drug-eluting bead (DEB) product developed in China; meanwhile, DEB-transarterial chemoembolization (TACE) with CSM is effective and safe in the treatment of hepatocellular carcinoma and intrahepatic cholangiocarcinoma."	( Irinotecan eluting beads-transarterial chemoembolization using Callispheres® microspheres is an effective and safe approach in treating unresectable colorectal cancer liver metastases. Bian, J; Liu, S; Wang, R; Wu, J; Zhang, Y; Zhao, G; Zhao, T; Zhou, J, 2022)	2.16
" Postoperative treatment response (including complete response rate (CR), objective response rate (ORR), and disease control rate (DCR)), survival data (overall survival (OS)), liver function, and adverse events were documented during the follow-up."	( Irinotecan eluting beads-transarterial chemoembolization using Callispheres® microspheres is an effective and safe approach in treating unresectable colorectal cancer liver metastases. Bian, J; Liu, S; Wang, R; Wu, J; Zhang, Y; Zhao, G; Zhao, T; Zhou, J, 2022)	2.16
" No grade 3 or grade 4 adverse event was observed, and main adverse events included fever (95."	( Irinotecan eluting beads-transarterial chemoembolization using Callispheres® microspheres is an effective and safe approach in treating unresectable colorectal cancer liver metastases. Bian, J; Liu, S; Wang, R; Wu, J; Zhang, Y; Zhao, G; Zhao, T; Zhou, J, 2022)	2.16
" 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
" However, its strong adverse effects, such as gastrointestinal and hepatic toxicities, tend to reduce the patients' life qualities and to limit the clinical use of CPT-11."	( Selenium-enriched Bifidobacterium longum DD98 attenuates irinotecan-induced intestinal and hepatic toxicity in vitro and in vivo. Chen, D; Gao, F; Kan, S; Lu, C; Qian, Z; Yin, Y; Zhu, H, 2021)	0.87
" Associations between PK exposure and the incidence of diarrhea (grade ≥3) and neutropenia adverse events (AEs) (grade ≥3) at first event in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) were investigated using logistic regression based on data from two studies (the phase III NAPOLI-1 [N = 260] and phase I/II NCT02551991 [N = 56] trials)."	( Population pharmacokinetics of liposomal irinotecan in patients with cancer and exposure-safety analyses in patients with metastatic pancreatic cancer. Bekaii-Saab, T; Boland, PM; Brendel, K; Dayyani, F; Dean, A; Macarulla, T; Maxwell, F; Mody, K; Pedret-Dunn, A; Wainberg, ZA; Zhang, B, 2021)	0.89
" 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)	0.96
"In this study, IR had some toxic effects in rat testis tissue; these effects were ameliorated by CRC treatment."	( Curcumin protects against testis-specific side effects of irinotecan. Aydın, M; Başak, N; Çetin, A; Çiftci, O; Gökhan Turtay, M; Gürbüz, Ş; Oğuztürk, H; Uyanık, Ö; Yücel, N, 2021)	0.87
"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)	0.94
" Pooled analyses for progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR) and grade 3/4 treatment-emergent adverse events (TRAEs) were undertaken."	( Efficacy and safety of FOLFIRINOX as second-line chemotherapy for advanced pancreatic cancer after gemcitabine-based therapy: A systematic review and meta-analysis. Li, X; Lu, W; Tang, K; Wang, L, 2022)	0.72
" However, grade 3/4 adverse events were more frequently reported in patients administered FOLFIRINOX compared with the other three regimens."	( Efficacy and safety of FOLFIRINOX as second-line chemotherapy for advanced pancreatic cancer after gemcitabine-based therapy: A systematic review and meta-analysis. Li, X; Lu, W; Tang, K; Wang, L, 2022)	0.72
" We assessed the indicators of tumour response, progression-free survival (PFS), overall survival (OS), and the incidence of adverse events."	( Treatment of unresectable intrahepatic cholangiocarcinoma using transarterial chemoembolisation with irinotecan-eluting beads: analysis of efficacy and safety. Liu, D; Ma, Z; Wang, J; Wen, Z; Xie, H; Yang, X; Zhang, N; Zhao, Y, 2022)	0.94
" Transient elevation of the aminotransferase level, nausea, vomiting, abdominal pain, fever, and hyper-bilirubinaemia were common adverse events in patients with unresectable ICC treated with DEB-TACE with CalliSphere beads (CBs)."	( Treatment of unresectable intrahepatic cholangiocarcinoma using transarterial chemoembolisation with irinotecan-eluting beads: analysis of efficacy and safety. Liu, D; Ma, Z; Wang, J; Wen, Z; Xie, H; Yang, X; Zhang, N; Zhao, Y, 2022)	0.94
"DEB-TACE with CBs is a safe and well-tolerated therapy in patients with unresectable ICC with a low incidence of adverse events and relatively prolonged survival."	( Treatment of unresectable intrahepatic cholangiocarcinoma using transarterial chemoembolisation with irinotecan-eluting beads: analysis of efficacy and safety. Liu, D; Ma, Z; Wang, J; Wen, Z; Xie, H; Yang, X; Zhang, N; Zhao, Y, 2022)	0.94
" 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)	1.15
" 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)	1.15
"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)	1.15
" We followed up these patients and analyzed the relapse-free survival (RFS), overall survival (OS), and chemotherapy-induced adverse events (AEs)."	( A Single-Center Retrospective Study to Compare the Efficacy and Safety of Modified FOLFIRINOX with S-1 as Adjuvant Chemotherapy in 71 Patients with Resected Pancreatic Carcinoma. Dai, H; Feng, W; Tang, C; Yao, L, 2022)	0.72
" The rate of adverse reactions such as hematological toxicity, neutropenia, anemia, thrombocytopenia, nonhematological toxicity, vomiting, fatigue, infection, diarrhea, intestinal obstruction, and peripheral neuropathy was lower in 10."	( Efficacy, Safety, and Impact on Patient Survival of PDL1/PD-1 Inhibitors versus FOLFIRINOX Regimens for Advanced Pancreatic Cancer. Dai, S; Jiang, C; Wu, Z; Zhou, L, 2022)	0.72
"PDL1/PD-1 inhibitors in combination with FOLFIRINOX regimens have shown longer survival than treatment with FOLFIRINOX regimens for pancreatic cancer patients, with reliable clinical efficacy, tolerable adverse effects, and a high safety profile for patients."	( Efficacy, Safety, and Impact on Patient Survival of PDL1/PD-1 Inhibitors versus FOLFIRINOX Regimens for Advanced Pancreatic Cancer. Dai, S; Jiang, C; Wu, Z; Zhou, L, 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)	0.97
" 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)	0.97
" 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)	1.03
" 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)	1.03
"Gastrointestinal mucositis (GIM) is a side effect of high-dose irinotecan (CPT-11), causing debilitating symptoms that are often poorly managed."	( Effects of a novel toll-like receptor 4 antagonist IAXO-102 in a murine model of chemotherapy-induced gastrointestinal toxicity. Bowen, JM; Coller, JK; Crame, EE; Elz, AS; Prestidge, CA; Tam, JSY; Wignall, A, 2022)	0.96
" 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)	1.17
"Our results provide preliminary evidence that HAIC based on FOLFIRI regimen is efficient and safe in some patients progressing after previous treatment."	( The Efficacy and Safety of Hepatic Arterial Infusion Chemotherapy Based on FOLFIRI for Advanced Intrahepatic Cholangiocarcinoma as Second-Line and Successive Treatment: A Real-World Study. Chen, Y; Huang, P; Huang, X; Shi, G; Sun, Q; Yang, G; Zhou, Y, 2022)	0.72
" No unexpected adverse events clinically, or permanent end-organ damage during postmortem examination was identified in glioma subjects who had received standard or prolonged duration of BEV, TMZ or TIB regimen-based chemotherapies except rare events of bone marrow suppression."	( Postmortem study of organ-specific toxicity in glioblastoma patients treated with a combination of temozolomide, irinotecan and bevacizumab. Ballester, LY; Bhattacharjee, MB; Brown, RE; Buja, LM; Chen, L; Glass, WF; Hergenroeder, GW; Hunter, RL; Linendoll, N; Lu, G; Pilichowska, M; Pillai, AK; Rao, M; Tian, X; Wu, JK; Zhang, R; Zhu, JJ; Zhu, P, 2022)	0.93
"03) was associated with adverse PFS."	( A nationwide evaluation of bevacizumab-based treatments in pediatric low-grade glioma in the UK: Safety, efficacy, visual morbidity, and outcomes. Ahmed, R; Bailey, S; Bowman, R; Carceller, F; Collins, R; Corley, E; D'Arco, F; Dahl, C; English, M; Green, K; Hargrave, D; Howells, L; Jorgensen, M; Kamal, A; Kilday, JJ; Lowis, S; Lumb, B; O'Hare, P; Opocher, E; Pace, E; Panagopoulou, P; Patel, P; Picton, S; Pizer, B; Shafiq, A; Slater, O; Uzunova, L; Walters, B; Wayman, H; Wilson, S, 2023)	0.91
" 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)	1.41
"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)	1.31
"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)	1.31
" 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)	1.31
" Using Clalit Health Services electronic medical records (including laboratory results) we ascertained hematological and gastrointestinal adverse effects and mortality, within 90 days of the first dose, as a composite outcome."	( Association Between ABCG2, ABCB1, ABCC2 Efflux Transporter Single-Nucleotide Variants and Irinotecan Adverse Effects in Patients With Colorectal Cancer: A Real-Life Study. Barnett-Griness, O; Gronich, N; Lejbkowicz, F; Pinchev, M; Rennert, G; Saliba, W, 2023)	1.13
" 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)	1.17
" None of the patients discontinued the study due to adverse events."	( Safety and efficacy of trastuzumab biosimilar plus irinotecan or gemcitabine in patients with previously treated HER2 (ERBB2)-positive non-breast/non-gastric solid tumors: a phase II basket trial with circulating tumor DNA analysis. Ahn, JH; Chun, SM; Hong, YS; Hyung, J; Jang, JP; Jeon, S; Jeong, JH; Jun, HR; Jung, CK; Kim, J; Kim, JE; Kim, TW; Lee, JY; Yoo, C; Yoon, S, 2023)	1.16
"Trastuzumab plus irinotecan or gemcitabine was safe and feasible for patients with previously treated HER2-positive advanced solid tumors with modest efficacy outcomes, and ctDNA analysis was useful for detecting HER2 amplification."	( Safety and efficacy of trastuzumab biosimilar plus irinotecan or gemcitabine in patients with previously treated HER2 (ERBB2)-positive non-breast/non-gastric solid tumors: a phase II basket trial with circulating tumor DNA analysis. Ahn, JH; Chun, SM; Hong, YS; Hyung, J; Jang, JP; Jeon, S; Jeong, JH; Jun, HR; Jung, CK; Kim, J; Kim, JE; Kim, TW; Lee, JY; Yoo, C; Yoon, S, 2023)	1.5

Pharmacokinetics

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. Body-surface area (BSA) is not a predictor of irinotecans pharmacokinetics.

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)	0.52
"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)	0.52
" 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)	0.29
" 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)	0.55
"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)	0.76
" 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)	0.54
"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)	0.54
"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
" 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
"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)	0.53
" 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)	0.49
"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)	0.84
"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)	0.79
" 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)	0.56
" 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)	0.56
" 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)	0.55
"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)	0.76
" 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)	0.59
"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)	0.3
"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
"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)	1.49
"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)	0.8
" 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)	0.57
" 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)	0.81
" 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)	0.53
" 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)	0.59
" 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)	0.53
"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)	1.97
"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)	0.77
" 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)	0.82
" 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)	0.59
"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)	0.77
" 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)	0.78
"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)	0.78
" 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)	0.7
" 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)	0.51
" 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)	0.93
" 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)	0.64
" 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)	0.55
"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)	0.77
" 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)	0.56
" 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)	0.61
"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)	0.54
" 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
"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)	1.97
"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)	0.86
"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)	0.61
" 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)	0.6
"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)	0.82
" 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)	0.61
"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)	0.84
" 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)	0.59
"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)	0.8
" 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)	0.57
"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)	0.81
" 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)	0.59
"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)	0.82
" 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)	0.57
"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)	0.8
" 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)	0.85
" 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)	0.84
" 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)	0.78
"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)	0.81
"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)	0.79
" 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, )	0.47
" 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)	0.78
" 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)	0.8
" 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)	0.83
" 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)	0.8
"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)	3.2
" 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)	1.76
" 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)	0.55
"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)	0.59
" 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
" 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)	0.87
" 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)	0.81
"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)	0.66
" 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)	0.59
" 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)	0.59
"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)	0.86
" 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)	1.48
" 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)	0.33
" 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)	0.82
"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)	0.76
" 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)	0.82
" 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)	0.74
" 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)	0.78
" 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)	0.57
" 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)	1.77
"Human pharmacokinetic parameters are often predicted prior to clinical study from in vivo preclinical pharmacokinetic data."	( Extrapolation of human pharmacokinetic parameters from rat, dog, and monkey data: Molecular properties associated with extrapolative success or failure. Jolivette, LJ; Ward, KW, 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)	0.83
" 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)	0.59
" 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)	0.59
" 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)	0.56
"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)	0.79
" 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, )	0.41
"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)	0.79
" 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)	0.92
"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)	0.33
"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)	0.33
" 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)	0.33
"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)	0.33
" 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, )	0.39
" 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)	0.86
"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
"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)	0.75
" 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)	1.11
" 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)	0.82
" 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)	0.57
" 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)	0.56
" 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)	1.78
" 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)	0.59
" 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)	0.59
" 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)	0.59
" 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)	0.57
"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)	0.77
" 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)	0.58
"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)	1.97
"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)	1.78
"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)	1.97
" 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)	0.78
" 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)	0.58
" 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)	0.76
" 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)	1.78
" 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)	1.78
"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)	0.77
" 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)	0.54
" 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)	0.54
"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)	0.86
"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)	0.92
"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)	0.67
" 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)	2.08
"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)	2.03
"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)	0.8
" pharmacokinetic data on 670 drugs representing, to our knowledge, the largest publicly available set of human clinical pharmacokinetic data."	( Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds. Lombardo, F; Obach, RS; Waters, NJ, 2008)	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)	0.91
" 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)	0.63
"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)	0.85
" 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)	0.57
" 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)	0.84
" 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)	0.86
" 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)	0.56
" 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)	0.81
"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)	0.78
" 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)	0.57
" 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)	0.57
" 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)	0.57
" 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)	0.57
" 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)	0.57
" 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)	0.62
" 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)	0.59
"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)	0.76
"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
" 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)	0.6
" 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)	0.61
" 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)	0.61
" 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)	0.64
" 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)	0.56
" 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)	0.63
" 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)	0.63
" 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)	0.61
" 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)	0.92
"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)	0.62
"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)	2.02
" 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)	2.06
" 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)	0.63
" 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)	0.63
"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)	0.92
" 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)	0.6
" 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)	0.61
" 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)	0.61
" 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)	0.83
" 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)	0.63
" 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)	0.63
"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)	0.8
"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)	0.9
" 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)	0.68
" 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)	0.6
" 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)	0.9
" 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
" 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)	0.62
"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)	0.6
" 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)	0.91
" 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)	0.84
"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)	0.63
" 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)	0.86
" 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
" 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)	0.89
" 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)	0.64
"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)	0.87
" 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)	0.65
"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)	0.87
"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)	0.87
" 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)	0.65
"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)	0.87
"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)	0.96
"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)	0.71
"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)	0.82
"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)	0.84
" 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)	0.7
" 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
" Irinotecan therapy is characterized by several dose-limiting toxicities and large interindividual pharmacokinetic variability."	( Individualization of Irinotecan Treatment: A Review of Pharmacokinetics, Pharmacodynamics, and Pharmacogenetics. Bins, S; de Man, FM; Goey, AKL; Mathijssen, RHJ; van Schaik, RHN, 2018)	1.71
" 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)	0.95
" Pharmacokinetic models to describe IRI and SN-38 kinetic profiles are available, with few studies exploring pharmacokinetic and pharmacogenetic-based dose individualization."	( Pharmacokinetic and Pharmacogenetic Markers of Irinotecan Toxicity. Antunes, MV; Hahn, RZ; Linden, R; Perassolo, MS; Schwartsmann, G; Suyenaga, ES; Verza, SG, 2019)	0.77
" The use of dried blood spot sampling could allow the clinical application of limited sampling and population pharmacokinetic models for IRI doses individualization."	( Pharmacokinetic and Pharmacogenetic Markers of Irinotecan Toxicity. Antunes, MV; Hahn, RZ; Linden, R; Perassolo, MS; Schwartsmann, G; Suyenaga, ES; Verza, SG, 2019)	0.77
"We used multiplexed targeted-mass-spectrometry to select pRAD50(Ser635) as a pharmacodynamic biomarker for AZD0156-mediated ATM inhibition from a panel of 45 peptides, then developed and tested a clinically applicable immunohistochemistry assay for pRAD50(Ser635) detection in FFPE tissue."	( pRAD50: a novel and clinically applicable pharmacodynamic biomarker of both ATM and ATR inhibition identified using mass spectrometry and immunohistochemistry. Barrett, JC; Cadogan, EB; Garcia-Trinidad, A; Griffin, N; Harrington, EA; Howat, WJ; Hughes, GD; Ivey, RG; Jones, GN; Lau, A; Odedra, R; Paulovich, AG; Pierce, AJ; Ramos-Montoya, A; Rooney, C; Roudier, M; Whiteaker, JR; Wilson, Z; Young, LA; Zhao, L, 2018)	0.48
" Study description, pharmacokinetic parameter values and influential covariates are reported."	( Population pharmacokinetics of FOLFIRINOX: a review of studies and parameters. Barbolosi, D; Deyme, L; Gattacceca, F, 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)	0.79
" The concentrations and pharmacokinetic parameters of the parent compound and its metabolite administered at clinically applicable dose via the intravenous route in the tumor tissue are predicted using this approach."	( Enzyme and Transporter Kinetics for CPT-11 (Irinotecan) and SN-38: An Insight on Tumor Tissue Compartment Pharmacokinetics Using PBPK. Ahmad, T; Ahmed, M; Chen, ZS; Czejka, M; Fan, Y; Khan, RA; Mansoor, N; Sharib, S; Wu, ZX; Yang, DH, 2019)	0.78
" 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)	0.87
" 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)	1.02
"To evaluate pharmacokinetic and safety profile of LifePearl microspheres loaded with irinotecan (LifePearl-IRI) in the treatment of liver-dominant, metastatic colorectal carcinoma (LM-CRC) by transarterial chemoembolization."	( LifePearl microspheres loaded with irinotecan in the treatment of Liver-dominant metastatic colorectal carcinoma: feasibility, safety and pharmacokinetic study. Helmberger, T; Isailovic, TV; Maleux, G; Pereira, P; Prenen, H; Spriet, I, 2020)	1.06
" 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)	0.86
"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)	1.13
" 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)	0.9
" 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)	1.1
" Over the last 10 years, the pharmacokinetic and pharmacodynamic profile of panitumumab has been studied to further evaluate its safety, efficacy, and optimal dosing regimen."	( Panitumumab: A Review of Clinical Pharmacokinetic and Pharmacology Properties After Over a Decade of Experience in Patients with Solid Tumors. Dutta, S; Kast, J; Upreti, VV, 2021)	0.62
" Here, we introduce a novel tumour-on-chip microfluidic system that mimics the pharmacokinetic profile of compounds on 3D tumour spheroids to evaluate their response to the treatments."	( Tumour-on-chip microfluidic platform for assessment of drug pharmacokinetics and treatment response. Ashford, M; Cadogan, E; Critchlow, S; Hughes, G; Lau, A; O'Connor, MJ; Oplustil O'Connor, L; Petreus, T; Pilla Reddy, V; Smith, A, 2021)	0.62
"Body surface area (BSA)-based dosing of irinotecan (IR) does not account for its pharmacokinetic (PK) and pharmacodynamic (PD) variabilities."	( Evaluation of pharmacogenomics and hepatic nuclear imaging-related covariates by population pharmacokinetic models of irinotecan and its metabolites. Beale, PJ; Burge, ME; Campbell, I; Crowley, S; Cullinane, C; Hatzimihalis, A; Hicks, RJ; Jefford, M; Karapetis, CS; Liauw, W; Link, E; Liu, Z; Martin, JH; Matera, A; McLachlan, SA; Michael, M; Price, T; Thompson, M, 2022)	1.2
" A stepwise analytical framework including a population pharmacokinetic model with SNP- and gene-based testing was used to identify demographic/clinical/genetic factors that influence the clearance of irinotecan and SN-38."	( Integration of DNA sequencing with population pharmacokinetics to improve the prediction of irinotecan exposure in cancer patients. Bies, RR; Cecchin, E; Cox, NJ; Etheridge, AS; Forrest, A; Innocenti, F; Karas, S; Mathijssen, RHJ; Mohlke, KL; Nickerson, DA; Toffoli, G, 2022)	1.13
" A population pharmacokinetic (PK) model was developed based on data from seven studies (N = 440)."	( Population pharmacokinetics of liposomal irinotecan in patients with cancer and exposure-safety analyses in patients with metastatic pancreatic cancer. Bekaii-Saab, T; Boland, PM; Brendel, K; Dayyani, F; Dean, A; Macarulla, T; Maxwell, F; Mody, K; Pedret-Dunn, A; Wainberg, ZA; Zhang, B, 2021)	0.89
" 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)	1.16
" However, systematic evaluation of potential pharmacodynamic interactions among multi-drug therapy has not been reported previously."	( FOLFIRINOX Pharmacodynamic Interactions in 2D and 3D Pancreatic Cancer Cell Cultures. Allen-Coyle, TJ; Clynes, M; Conlon, NT; Garner, W; Mager, DE; Niu, J; O'Sullivan, F; Roche, S; Straubinger, RM; Welsch, E, 2022)	0.72
"There have been many attempts in pharmaceutical industries and academia to improve the pharmacokinetic characteristics of anti-tumor small-molecule drugs by conjugating them with large molecules, such as monoclonal antibodies, called ADCs."	( Evaluation of In Vivo Prepared Albumin-Drug Conjugate Using Immunoprecipitation Linked LC-MS Assay and Its Application to Mouse Pharmacokinetic Study. Hwang, S; Jo, E; Lee, J; Lee, Y; Lim, JH; Park, M; Park, SJ; Park, Y; Shin, YG, 2023)	0.91

Compound-Compound Interactions

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. Pharmacokinetic data suggested a decreased metabolism of irinOTecan into SN-38 and SN- 38-glucuronide when it was administered with thalidomide.

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)	0.28
" 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)	0.61
" 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)	0.59
"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)	0.92
"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)	0.3
" 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)	0.63
" 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)	0.63
"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)	1.74
"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)	1.74
"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)	0.9
" 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)	0.73
"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)	1.98
" 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)	1.75
"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)	0.86
" 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)	0.64
" 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)	0.89
"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)	3.19
"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)	0.77
"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)	0.82
"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
" 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)	0.67
" 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)	0.85
" 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)	0.85
") 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)	0.62
"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, )	0.43
" 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)	1.76
" 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)	0.74
"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)	0.88
" 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)	0.85
" 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)	0.5
" 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)	0.79
" 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)	0.84
"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)	0.82
" 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)	1.97
" 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)	1.99
"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)	3.2
"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)	2.01
"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)	0.57
" 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)	0.93
"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)	2
" 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)	0.52
" 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)	2.14
"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)	0.87
" 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)	1.46
" 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
"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)	0.77
"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)	0.81
" 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)	0.32
" 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)	0.75
"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)	0.83
"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)	0.88
"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)	0.96
"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)	0.66
" 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)	0.57
" 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)	0.82
"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)	0.78
" 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)	0.59
"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)	0.78
"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)	0.56
"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)	0.8
"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)	0.8
" 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)	1.07
"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)	0.82
" 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)	0.76
" 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)	0.61
" 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)	0.61
"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)	0.81
" 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)	2.01
"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)	1.77
"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)	1.24
" 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)	1.24
"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)	0.79
"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)	0.77
" 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)	0.56
" 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)	0.51
" 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)	0.76
"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, )	1.85
"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)	0.9
"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)	0.73
" 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)	0.77
"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)	2.06
" 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)	0.87
" 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)	0.56
" 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)	0.76
"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)	0.74
" 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)	0.9
"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)	0.57
"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, )	0.67
" 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)	0.76
"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)	0.93
"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)	2.02
" 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)	2.02
" 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)	0.85
"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, )	0.66
" 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)	0.57
" 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, )	0.37
" 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)	0.78
"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)	2.03
"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)	0.8
" 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)	0.78
"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)	0.8
"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)	0.8
" 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)	0.78
" 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)	0.57
" 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)	0.75
"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)	0.82
"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)	0.86
"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)	0.83
"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)	0.77
"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)	0.83
"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)	0.88
"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)	0.93
"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)	0.9
"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)	0.58
"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)	0.52
" 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)	0.75
"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)	0.71
"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)	0.72
"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)	0.74
"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)	0.78
"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)	0.77
"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)	0.54
"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)	0.54
" 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)	0.77
" 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)	0.54
"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)	0.88
"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)	0.93
" 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)	0.56
" 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)	0.86
" 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)	1.52
"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)	2.1
"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)	0.59
"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)	0.58
"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)	0.58
" 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
" 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)	2.07
" 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)	0.77
"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)	0.82
"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)	0.81
"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)	0.94
" 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)	0.85
" 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)	0.82
"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)	0.92
"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)	0.84
"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)	0.86
"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)	0.83
"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)	0.85
"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)	0.83
"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)	0.88
" 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)	0.76
" 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)	0.82
"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)	0.8
" 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)	0.55
"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)	0.74
"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)	0.79
" 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)	1.59
"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)	0.89
"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)	0.68
" 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)	0.83
" 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)	0.83
"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)	0.57
" 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)	0.57
" 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)	0.6
"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)	0.6
" 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)	0.84
" 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)	2.06
"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)	2.06
"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)	2.32
"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)	0.74
" 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)	0.57
"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)	0.57
" 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)	1.03
" 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)	0.8
"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)	0.56
"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
" 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)	0.89
"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)	0.84
" 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)	0.86
"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)	0.89
"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)	0.94
"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)	0.76
"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)	0.75
"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, )	0.34
"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, )	0.34
" 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
" 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)	0.88
" 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)	0.96
"The hepatic organic anion transporting polypeptides (OATPs) influence the pharmacokinetics of several drug classes and are involved in many clinical drug-drug interactions."	( Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. Artursson, P; Haglund, U; Karlgren, M; Kimoto, E; Lai, Y; Norinder, U; Vildhede, A; Wisniewski, JR, 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)	0.6
"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)	0.58
"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)	0.78
" 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)	0.85
" 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)	0.59
" 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)	0.83
" 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)	0.59
"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)	0.61
"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)	0.88
"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)	0.91
"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)	0.83
" 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)	0.86
" 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)	0.89
" 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
"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)	0.61
" 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)	1.83
" 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)	0.8
" 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)	0.89
"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)	0.84
"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)	0.63
"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)	0.79
"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)	0.84
"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)	0.99
"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)	0.84
"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)	0.68
" 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
" 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)	0.83
"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)	0.83
"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)	0.85
" 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)	0.89
" 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)	0.89
"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)	0.68
" 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)	0.93
"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
"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)	1.07
" 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)	0.86
"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)	0.64
"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)	0.84
" 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)	0.87
"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)	0.9
" 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)	0.67
" 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)	0.61
"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)	0.66
"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)	0.68
"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)	0.65
" 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)	0.82
" 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)	0.94
"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)	0.9
"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)	2.11
"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)	1.88
" 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)	0.89
"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)	0.93
" 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)	0.63
" 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)	0.66
"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)	0.82
"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)	0.86
" 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)	0.86
" 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)	0.86
" 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
"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)	0.87
"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)	0.91
" 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)	0.8
"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)	0.62
" 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)	0.68
"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)	0.94
"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)	0.75
"An intestine-liver-glioblastoma biomimetic system was developed to evaluate the drug combination therapy for glioblastoma."	( Evaluation of drug combination for glioblastoma based on an intestine-liver metabolic model on microchip. He, Z; Jie, M; Li, HF; Lin, JM; Liu, H; Mao, S, 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)	0.7
"CCK-8 assay and flow cytometry were used to assess the effects of bFGF mAb combined with irinotecan on the proliferation and apoptosis of H223 cells, respectively."	( [Effect of basic fibroblast growth factor antibody combined with irinotecan on proliferation and apoptosis of small cell lung cancer H223 cells in vitro]. Liao, XH; Xiang, JJ; Xu, M, 2017)	0.91
" A prospective clinical trial was designed to evaluate the efficacy and safety of fluorouracil monotherapy combined with panitumumab administered to patients with KRAS wild-type (WT) metastatic colorectal cancer (mCRC) intolerant to oxaliplatin and irinotecan."	( A phase II trial to evaluate the efficacy of panitumumab combined with fluorouracil-based chemotherapy for metastatic colorectal cancer: the PF trial. Denda, T; Fukunaga, M; Kanda, M; Kataoka, M; Kim, HM; Mishima, H; Munemoto, Y; Nagata, N; Oba, K; Sakamoto, J; Takano, N; Takemoto, H; Tokunaga, Y, 2018)	0.66
" Panitumumab (6 mg/kg) was intravenously administered every 2 weeks, combined with fluorouracil monotherapy, in 2-week cycles."	( A phase II trial to evaluate the efficacy of panitumumab combined with fluorouracil-based chemotherapy for metastatic colorectal cancer: the PF trial. Denda, T; Fukunaga, M; Kanda, M; Kataoka, M; Kim, HM; Mishima, H; Munemoto, Y; Nagata, N; Oba, K; Sakamoto, J; Takano, N; Takemoto, H; Tokunaga, Y, 2018)	0.48
"5%) met eligibility criteria and received 7 cycles (median) of fluorouracil chemotherapy combined with panitumumab."	( A phase II trial to evaluate the efficacy of panitumumab combined with fluorouracil-based chemotherapy for metastatic colorectal cancer: the PF trial. Denda, T; Fukunaga, M; Kanda, M; Kataoka, M; Kim, HM; Mishima, H; Munemoto, Y; Nagata, N; Oba, K; Sakamoto, J; Takano, N; Takemoto, H; Tokunaga, Y, 2018)	0.48
"Fluorouracil monotherapy combined with panitumumab was safely administered to patients with KRAS WT mCRC intolerant to oxaliplatin and irinotecan."	( A phase II trial to evaluate the efficacy of panitumumab combined with fluorouracil-based chemotherapy for metastatic colorectal cancer: the PF trial. Denda, T; Fukunaga, M; Kanda, M; Kataoka, M; Kim, HM; Mishima, H; Munemoto, Y; Nagata, N; Oba, K; Sakamoto, J; Takano, N; Takemoto, H; Tokunaga, Y, 2018)	0.68
"The last decade has seen the increasing use of biological medicines in combination with chemotherapy containing 5-fluorouracil/oxaliplatin or irinotecan for the treatment of metastatic colorectal cancer (mCRC)."	( Comparative Effectiveness and Safety of Monoclonal Antibodies (Bevacizumab, Cetuximab, and Panitumumab) in Combination with Chemotherapy for Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis. Almeida, PHRF; Andrade, EIG; Cherchiglia, ML; da Silva, WC; de Araujo, VE; de Assis Acurcio, F; Dos Santos, JBR; Godman, B; Kurdi, A; Lima, EMEA; Silva, MRRD, 2018)	0.68
" 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)	1.05
"This study aimed to examine the efficacy of metabolically supported administration of chemotherapy combined with ketogenic diet, hyperthermia, and hyperbaric oxygen therapy (HBOT) in patients with metastatic pancreatic cancer."	( Long-Term Survival Outcomes of Metabolically Supported Chemotherapy with Gemcitabine-Based or FOLFIRINOX Regimen Combined with Ketogenic Diet, Hyperthermia, and Hyperbaric Oxygen Therapy in Metastatic Pancreatic Cancer. Iyikesici, MS, 2020)	0.56
"Anti-EGFR MoAbs as a monotherapy or in combination with either irinotecan-based chemotherapy or FOLFOX in patients with RAS wild-type mCRC have better response and survival outcome, whereas OS does not benefit from adding anti-EGFR MoAbs to another oxaliplatin-based regimen."	( Efficacy and safety of anti-EGFR monoclonal antibodies combined with different chemotherapy regimens in patients with RAS wild-type metastatic colorectal cancer: A meta-analysis. Han, J; Li, J; Li, Y; Su, Y; Sun, H; Wu, X; Zhou, X, 2019)	0.75
" We hypothesized that pelareorep in combination with pembrolizumab and chemotherapy in patients with PDAC would be safe and effective."	( Pembrolizumab in Combination with the Oncolytic Virus Pelareorep and Chemotherapy in Patients with Advanced Pancreatic Adenocarcinoma: A Phase Ib Study. Arora, SP; Cheetham, K; Coffey, M; Eng, KH; Fields, P; Fountzilas, C; Kalinski, P; Mahalingam, D; Moseley, JL; Nuovo, G; Raber, P; Wilkinson, GA; Zhang, B, 2020)	0.56
" Particularly, the expression of tumour-suppressing gene Ccdc80 was induced by vactosertib and further induced by vactosertib in combination with nal-IRI/5-FU/LV."	( Inhibition of TGF-β signalling in combination with nal-IRI plus 5-Fluorouracil/Leucovorin suppresses invasion and prolongs survival in pancreatic tumour mouse models. An, H; Heo, JS; Hong, CP; Hong, E; Kang, JM; Kim, SJ; Lee, S; Ooshima, A; Park, J; Park, JO; Park, S; Park, SH, 2020)	0.56
"Vincristine combined with camptothecin derivatives showed synergy in preclinical pediatric cancer models, and the combinations are effective in treatment of childhood solid tumors."	( Evaluation of Eribulin Combined with Irinotecan for Treatment of Pediatric Cancer Xenografts. Bandyopadhyay, A; Chen, Y; Erickson, SW; Houghton, PJ; Kurmashev, D; Kurmasheva, RT; Lai, Z; Phelps, DA; Robles, AJ; Smith, MA, 2020)	0.83
"Vincristine or eribulin, alone or combined with irinotecan, was studied in 12 xenograft models."	( Evaluation of Eribulin Combined with Irinotecan for Treatment of Pediatric Cancer Xenografts. Bandyopadhyay, A; Chen, Y; Erickson, SW; Houghton, PJ; Kurmashev, D; Kurmasheva, RT; Lai, Z; Phelps, DA; Robles, AJ; Smith, MA, 2020)	1.09
"Eribulin combined with irinotecan was more effective than vincristine-irinotecan in 6 of 12 models."	( Evaluation of Eribulin Combined with Irinotecan for Treatment of Pediatric Cancer Xenografts. Bandyopadhyay, A; Chen, Y; Erickson, SW; Houghton, PJ; Kurmashev, D; Kurmasheva, RT; Lai, Z; Phelps, DA; Robles, AJ; Smith, MA, 2020)	1.14
" The drug combination administered at clinical doses resulted in significantly higher antagonistic interactions compared to the low-dose optimized drug combination (ODC)."	( Drug-Drug Interactions of Irinotecan, 5-Fluorouracil, Folinic Acid and Oxaliplatin and Its Activity in Colorectal Carcinoma Treatment. Nowak-Sliwinska, P; Ramzy, GM; Rausch, M; Zoetemelk, M, 2020)	0.86
" 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)	1.16
" This meta-analysis discusses the efficacy and side effects of BVZ combined with irinotecan in the treatment of patients (younger than 21 years of age) with recurrent, progressive or refractory intracranial tumours."	( Therapeutic effect and side effects of Bevacizumab combined with Irinotecan in the treatment of paediatric intracranial tumours: Meta-analysis and Systematic Review. Di, F; Li, Q; Ma, HY; Sun, T; Xiang, RL; Xu, Y, 2020)	1.02
"BVZ combined with irinotecan-based chemotherapy had a better response and prolonged survival in the treatment of paediatric intracranial tumours than radiation therapy or chemotherapy."	( Therapeutic effect and side effects of Bevacizumab combined with Irinotecan in the treatment of paediatric intracranial tumours: Meta-analysis and Systematic Review. Di, F; Li, Q; Ma, HY; Sun, T; Xiang, RL; Xu, Y, 2020)	1.13
" The current study aimed to evaluate the effects of anlotinib in combination with irinotecan on H446 and H2227 SCLC cell lines and provide new treatment strategy for SCLC."	( A novel multi-target tyrosine kinase inhibitor anlotinib combined with irinotecan has in-vitro anti-tumor activity against human small-cell lung cancer. Cheng, Y; Li, H; Liu, J; Liu, X; Liu, Y; Zhao, D, 2020)	1.02
"To investigate the efficacy and safety of irinotecan combined with nedaplatin in the treatment of small cell lung cancer (SCLC)."	( The efficacy and safety of irinotecan combined with nedaplatin in the treatment of small cell lung cancer. Fang, S; Fu, J; Wang, D; Wang, Y; Wen, Y; Yin, X, )	0.69
" Thirty-two patients in group A were treated with irinotecan combined with nedaplatin, while 32 patients in group B were treated with irinotecan combined with cisplatin."	( The efficacy and safety of irinotecan combined with nedaplatin in the treatment of small cell lung cancer. Fang, S; Fu, J; Wang, D; Wang, Y; Wen, Y; Yin, X, )	0.68
"The efficacy of irinotecan combined with nedaplatin is good and the safety is high in the treatment of SCLC and it can be used as a clinical treatment method of SCLC and is worthy of being generalized."	( The efficacy and safety of irinotecan combined with nedaplatin in the treatment of small cell lung cancer. Fang, S; Fu, J; Wang, D; Wang, Y; Wen, Y; Yin, X, )	0.77
" We conducted a phase 1 trial to evaluate the safety of olaratumab and determine a recommended dose in combination with three different chemotherapy regimens in children."	( Phase 1 trial of olaratumab monotherapy and in combination with chemotherapy in pediatric patients with relapsed/refractory solid and central nervous system tumors. Bishop, MW; Borinstein, SC; DuBois, SG; Hingorani, P; Krystal, J; Laetsch, TW; Levy, DE; Mascarenhas, L; Mo, G; Muscal, JA; Ogawa, C; Shahir, A; Slotkin, EK; Weigel, BJ; Wright, J, 2021)	0.62
" Irreversible electroporation (IRE) is a nonthermal ablative technique that provides an alternative in patients with LAPC and can be safely combined with chemotherapy."	( Irreversible Electroporation (IRE) Combined With Chemotherapy Increases Survival in Locally Advanced Pancreatic Cancer (LAPC). Astras, G; Davakis, S; Dimitrokallis, N; Felekouras, E; Karamouzis, MV; Kountourakis, P; Moris, D; Oikonomou, D; Papalampros, A; Papamichael, D; Petrou, AS; Schizas, D, 2021)	0.62
"Administration of green tea (GT) catechins has been reported to ensue antitumor activity in combination with chemotherapeutic drugs against different cancer types."	( Green tea catechins in combination with irinotecan attenuates tumorigenesis and treatment-associated toxicity in an inflammation-associated colon cancer mice model. Bharali, MK; Borah, G, 2021)	0.89
"In this study, we investigated the antitumor effects of GT alone or in combination with IRN in inflammation-associated colon cancer mouse model induced by azoxymethane (AOM) and dextran sulfate sodium (DSS)."	( Green tea catechins in combination with irinotecan attenuates tumorigenesis and treatment-associated toxicity in an inflammation-associated colon cancer mice model. Bharali, MK; Borah, G, 2021)	0.89
" In this study, CPT11 alone or combined with dual-function inhibitors (baicalein (BA) silymarin (SM), glycyrrhizic acid (GA), and glycyrrhetinic acid (GLA)) of P-gp and CYP450 loaded in a lecithin-based self-nanoemulsifying nanoemulsion preconcentrate (LBSNENP) to improve the solubility and inhibit the elimination by P-gp and CYP450."	( CPT11 with P-glycoprotein/CYP 3A4 dual-function inhibitor by self-nanoemulsifying nanoemulsion combined with gastroretentive technology to enhance the oral bioavailability and therapeutic efficacy against pancreatic adenocarcinomas. Chen, LC; Cheng, WJ; Hsieh, CM; Hung, MT; Lin, HL; Lin, SY; Sheu, MT, 2021)	0.62
"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
"This detailed preclinical investigation, including pharmacokinetics/pharmacodynamics and dose-schedule optimizations, of AZD6738/ceralasertib alone and in combination with chemotherapy or PARP inhibitors can inform ongoing clinical efforts to treat cancer with ATR inhibitors."	( ATR Inhibitor AZD6738 (Ceralasertib) Exerts Antitumor Activity as a Monotherapy and in Combination with Chemotherapy and the PARP Inhibitor Olaparib. Bargh-Dawson, H; Brown, E; Gerrard, J; Hughes, AM; Jones, GN; Lau, A; O'Connor, MJ; Odedra, R; Wallez, Y; Wijnhoven, PWG; Wilson, Z; Young, LA, 2022)	0.72
" We therefore suggest that future studies should focus on elucidating the complex interplay between chemotherapy in combination with luminal irritants on the intestinal permeability of other probes."	( Chemotherapeutics Combined with Luminal Irritants: Effects on Small-Intestinal Mannitol Permeability and Villus Length in Rats. Cano-Cebrián, MJ; Dahlgren, D; Kullenberg, F; Lennernäs, H; Olander, T; Peters, K; Sjöblom, M, 2022)	0.72
"A case-control study was adopted to investigate the efficacy and side effects of irinotecan combined with nedaplatin (NP) versus paclitaxel combined with cisplatin for locally advanced cervical cancer (CC) neoadjuvant chemotherapy (NACT) and to analyze the changes in tumor marker levels."	( Efficacy and Side Effects of Irinotecan Combined with Nedaplatin versus Paclitaxel Combined with Cisplatin in Neoadjuvant Chemotherapy for Locally Advanced Cervical Cancer and Tumor Marker Analysis: Based on a Retrospective Analysis. Chen, Z; Jiang, Y; Song, B, 2022)	1.24
" Among them, 53 patients received paclitaxel combined with cisplatin as the control group, and the other 43 patients received irinotecan combined with NP as the observation group."	( Efficacy and Side Effects of Irinotecan Combined with Nedaplatin versus Paclitaxel Combined with Cisplatin in Neoadjuvant Chemotherapy for Locally Advanced Cervical Cancer and Tumor Marker Analysis: Based on a Retrospective Analysis. Chen, Z; Jiang, Y; Song, B, 2022)	1.22
"Irinotecan in combination with nedaplatin can be an effective neoadjuvant chemotherapy regimen for advanced localized cervical cancer, particularly in patients with combined diabetes."	( Efficacy and Side Effects of Irinotecan Combined with Nedaplatin versus Paclitaxel Combined with Cisplatin in Neoadjuvant Chemotherapy for Locally Advanced Cervical Cancer and Tumor Marker Analysis: Based on a Retrospective Analysis. Chen, Z; Jiang, Y; Song, B, 2022)	2.46
" In this study, we report the safety and efficacy of cetuximab (an epidermal growth factor receptor inhibitor) in combination with 5-FU plus irinotecan based chemotherapy."	( Efficacy and tolerance of cetuximab in combination with 5 FU plus irinotecan based chemotherapy in metastatic squamous cell anal carcinoma. Boige, V; Boilève, A; Cervantes, B; Ducreux, M; Hollebecque, A; Malka, D; Smolenschi, C; Valery, M, 2023)	1.35
" 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)	1.27
" 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)	1.21
"This study aimed to investigate the short-term efficacy and adverse reactions of irinotecan combined with first-line chemotherapeutics for the treatment of pediatric hepatoblastoma with pulmonary metastasis (HB-PM)."	( Clinical application of irinotecan combined with first-line chemotherapeutics against pediatric hepatoblastoma with pulmonary metastasis. Hu, H; Huang, D; Li, F; Li, J; Mei, Y; Wen, Y; Zhang, W, 2022)	1.25
" In this study, we aimed to assess the efficacy and safety of trastuzumab in combination with chemotherapy in HER2-positive metastatic colorectal cancer (mCRC)."	( Trastuzumab Combined with Irinotecan in Patients with HER2-Positive Metastatic Colorectal Cancer: A Phase II Single-Arm Study and Exploratory Biomarker Analysis. Bai, Y; Gong, J; Huang, D; Ji, C; Li, J; Li, Y; Shen, L; Sun, Y; Wang, X; Wang, Z; Xin, Y; Xu, T; Zhang, X; Zhao, F, 2023)	1.21
"Trastuzumab combined with chemotherapy is a potentially effective and well-tolerated therapeutic regimen in mCRC with a high HER2 copy number."	( Trastuzumab Combined with Irinotecan in Patients with HER2-Positive Metastatic Colorectal Cancer: A Phase II Single-Arm Study and Exploratory Biomarker Analysis. Bai, Y; Gong, J; Huang, D; Ji, C; Li, J; Li, Y; Shen, L; Sun, Y; Wang, X; Wang, Z; Xin, Y; Xu, T; Zhang, X; Zhao, F, 2023)	1.21
" F3 bromelain may be a potential and potent drug for clinical use due to its anticancer efficacy and high synergistic cytotoxicity when combined with a routine chemotherapeutic agent for CRC."	( Cytotoxic properties of unfractionated and fractionated bromelain alone or in combination with chemotherapeutic agents in colorectal cancer cells. Azarkan, M; Chang, YJ; Chen, HA; Huang, CY; M'Rabet, N; Makondi, PT; Tsai, KY; Wei, PL, 2023)	0.91
"This study aimed to investigate the mechanism of resveratrol(RES) combined with irinotecan(IRI) in the treatment of colorectal cancer(CRC)."	( [Molecular mechanism of resveratrol combined with irinotecan in treatment of colorectal cancer]. Han, CL; Li, F; Li, KY; Liu, M; Shen, H; Wang, J; Wang, L; Yan, RY, 2023)	1.39
" The objective of this study was to investigate the security and effectiveness of irinotecan combined with raltitrexed or irinotecan monotherapy for salvage chemotherapy of ESCC."	( Efficacy and safety of irinotecan combined with raltitrexed or irinotecan monotherapy for salvage chemotherapy of esophageal squamous cell cancer: A prospective, open label, randomized phase II study. Bian, W; Chen, S; Dai, X; Tao, L; Wang, J; Wu, W, 2023)	1.45
" Patients were randomly divided into irinotecan combined with raltitrexed group (experiment group) and irinotecan monotherapy group (control group)."	( Efficacy and safety of irinotecan combined with raltitrexed or irinotecan monotherapy for salvage chemotherapy of esophageal squamous cell cancer: A prospective, open label, randomized phase II study. Bian, W; Chen, S; Dai, X; Tao, L; Wang, J; Wu, W, 2023)	1.49
"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)	1.51
" The authors investigated which dose could be administered safely in combination with standard palliative chemotherapy."	( Phase I study of intraperitoneal irinotecan combined with palliative systemic chemotherapy in patients with colorectal peritoneal metastases. Bakkers, C; Bax, R; Brandt-Kerkhof, ARM; Buijs, SM; Burger, JWA; Creemers, GM; de Boer, NL; de Hingh, IHJT; de Man, FM; Diepeveen, M; Dietz, MV; Koolen, SLW; Lurvink, RJ; Mathijssen, RHJ; van Eerden, RAG; van Kooten, JP; van Meerten, E; Verhoef, C, 2023)	1.19
" We then evaluated the antitumor activity of MSLN-targeted CAR T cells alone or in combination with the chemotherapeutic drug irinotecan or an anti-PD-1 antibody in vitro and in vivo."	( Mesothelin-targeted CAR-T therapy combined with irinotecan for the treatment of solid cancer. Chen, L; Chen, X; Feng, M; He, H; Lan, S; Wang, K; Zhu, Y; Zuo, D, 2023)	1.37

Bioavailability

Irinotecan (IRN) (CPT-11) is a camptothecin derivative with low oral bioavailability due to active efflux by intestinal P-glycoprotein receptors. Inhibition of intestinal hCES2A can alleviate irinotacan-induced gut toxicity.

Excerpt	Reference	Relevance
" The drug is well absorbed from small intestine."	( [Topoisomerase inhibitors developing in Japan]. Furue, H, 1993)	0.29
"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)	0.3
" 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)	0.77
"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)	2.03
"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)	0.31
" 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)	0.58
" 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)	0.78
" 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)	1.78
"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)	0.35
" 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)	0.85
" 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)	0.86
" 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)	0.83
" 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)	0.83
" Compound 5 has a good oral bioavailability and effectively inhibits tumor growth in the SJSA-1 xenograft model."	( Potent and orally active small-molecule inhibitors of the MDM2-p53 interaction. Chen, J; Ding, K; Kang, S; McEachern, D; Miller, R; Nikolovska-Coleska, Z; Qin, D; Qiu, S; Shangary, S; Wang, G; Wang, S; Yang, D; Yu, S, 2009)	0.35
" 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
" 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
"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)	0.38
" 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
" 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)	0.87
" 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)	0.6
" A novel series of potent and orally bioavailable 3-alkoxyamino-5-(pyridin-2-ylamino)pyrazine-2-carbonitrile CHK1 inhibitors was generated by hybridization of two lead scaffolds derived from fragment-based drug design and optimized for CHK1 potency and high selectivity using a cell-based assay cascade."	( Discovery of 3-alkoxyamino-5-(pyridin-2-ylamino)pyrazine-2-carbonitriles as selective, orally bioavailable CHK1 inhibitors. Aherne, GW; Box, G; Boxall, KJ; Collins, I; de Haven Brandon, AK; Eccles, SA; Eve, PD; Garrett, MD; Hayes, A; Lainchbury, M; Matthews, TP; McHardy, T; Raynaud, FI; Reader, JC; Valenti, MR; Walton, MI, 2012)	0.38
" 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)	1.83
"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
" 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)	0.86
" 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
" 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)	0.82
" 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)	1.34
" 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
" 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)	0.46
"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)	2.21
" 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)	0.76
"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)	0.76
"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
" Dabigatran etexilate (DABE), an oral anticoagulant and substrate of P-glycoprotein (P-gp), is poorly absorbed and exhibits low bioavailability in humans."	( Irinotecan-induced gastrointestinal damage impairs the absorption of dabigatran etexilate. Akiyoshi, T; Hattori, T; Imaoka, A; Ohtani, H, 2019)	1.96
" However, it is unclear if the enteric bioavailability of SN-38 is mostly dependent on luminal SN-38 concentrations."	( Irinotecan-mediated diarrhea is mainly correlated with intestinal exposure to SN-38: Critical role of gut Ugt. Gao, S; Ghose, R; Gong, X; Hu, M; Li, L; Liu, Z; Qi, X; Song, W; Sun, R; Wang, Y; Zhu, L, 2020)	2
"Liposomal formulations may improve the solubility and bioavailability of drugs potentially increasing their ability to cross the blood-brain barrier."	( Nanoliposomal Irinotecan and Metronomic Temozolomide for Patients With Recurrent Glioblastoma: BrUOG329, A Phase I Brown University Oncology Research Group Trial. Baekey, J; Carcieri, A; Cielo, D; Disano, D; Donnelly, J; Elinzano, H; MacKinnon, K; Mohler, A; Robison, J; Safran, H; Sturtevant, A; Toms, S; Vatketich, J; Wood, R, 2021)	0.98
" However, the limited oral bioavailability of irinotecan poses a problem for its oral delivery."	( Possible roles of intestinal P-glycoprotein and cytochrome P450 3A on the limited oral absorption of irinotecan. Arimori, K; Furuya, Y; Hidaka, M; Kawano, Y; Ono, H; Yamasaki, K, 2021)	1.1
" Indeed, the oral bioavailability of irinotecan was increased when verapamil was orally pre-administered."	( Possible roles of intestinal P-glycoprotein and cytochrome P450 3A on the limited oral absorption of irinotecan. Arimori, K; Furuya, Y; Hidaka, M; Kawano, Y; Ono, H; Yamasaki, K, 2021)	1.11
" Although curcumin is known to have anti-tumor, hepatoprotective, and hypoglycemic-like actions, its low water solubility, oral absorption, and bioavailability impede its therapeutic uses."	( Anti-cancer activity of amorphous curcumin preparation in patient-derived colorectal cancer organoids. Abugomaa, A; Ayame, H; Elbadawy, M; Hayashi, K; Hayashi, SM; Hazama, S; Ishihara, Y; Kaneda, M; Nagano, H; Nakajima, M; Sasaki, K; Shibutani, M; Shinohara, Y; Suzuki, N; Takenouchi, H; Tsunedomi, R; Usui, T; Yamawaki, H, 2021)	0.62
" Pharmacokinetic study of CPT11-loaded PC90C10P0 administered orally revealed an absolute bioavailability (FAB, vs."	( CPT11 with P-glycoprotein/CYP 3A4 dual-function inhibitor by self-nanoemulsifying nanoemulsion combined with gastroretentive technology to enhance the oral bioavailability and therapeutic efficacy against pancreatic adenocarcinomas. Chen, LC; Cheng, WJ; Hsieh, CM; Hung, MT; Lin, HL; Lin, SY; Sheu, MT, 2021)	0.62
"AZD6738 (ceralasertib) is a potent and selective orally bioavailable inhibitor of ataxia telangiectasia and Rad3-related (ATR) kinase."	( ATR Inhibitor AZD6738 (Ceralasertib) Exerts Antitumor Activity as a Monotherapy and in Combination with Chemotherapy and the PARP Inhibitor Olaparib. Bargh-Dawson, H; Brown, E; Gerrard, J; Hughes, AM; Jones, GN; Lau, A; O'Connor, MJ; Odedra, R; Wallez, Y; Wijnhoven, PWG; Wilson, Z; Young, LA, 2022)	0.72
" Future studies should focus not only on developing other active molecules but also on improving the bioavailability and pharmacokinetics of potent synthetic derivatives."	( The design and discovery of topoisomerase I inhibitors as anticancer therapies. Alonso, C; Martín-Encinas, E; Palacios, F; Selas, A, 2022)	0.72
" Relative to the small-size nanocarrier, the size-transformable counterpart appeared to restrict the mucociliary and absorption clearances from the lung and the clearance from the tumor interstitium to circulation, leading to increases in lung and tumor bioavailability of SN38 by 58."	( Pulmonary delivery of size-transformable nanoparticles improves tumor accumulation and penetration for chemo-sonodynamic combination therapy. Chen, W; Cong, Z; Ge, D; Liao, Y; Ma, S; Wei, J; Yang, F, 2022)	0.72
" 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)	0.91
" The oral bioavailability of CEX significantly decreased to 76% of that in control rats."	( Irinotecan-induced gastrointestinal damage alters the expression of peptide transporter 1 and absorption of cephalexin in rats. Akiyoshi, T; Hattori, T; Imaoka, A; Ohtani, H, 2023)	2.35
" Inhibition of intestinal hCES2A can alleviate irinotecan-induced gut toxicity and modulate the oral bioavailability of hCES2A-substrate drugs."	( New bysspectin A derivatives as potent inhibitors of human carboxylesterase 2A. Ge, G; Jiao, X; Li, W; Lin, S; Liu, X; Ma, B; Song, Y; Wu, Y; Xie, P; Zhang, Y; Zhu, G, 2023)	1.17
"P-glycoprotein (Pgp) plays a pivotal role in drug bioavailability and multi-drug resistance development."	( Drug-Induced Conformational Dynamics of P-Glycoprotein Underlies the Transport of Camptothecin Analogs. Bartlett, MG; King, GM; Mensah, GAK; Roberts, AG; Schaefer, KG, 2023)	0.91

Dosage Studied

The marked variability of irinotecan (Ir) clearance warrants individualized dosing based on hepatic drug handling. Verapamil (25mg/kg) was administered orally 2h before irinOTecan oral or intravenous dosing in female Wistar rats. The EWG found adequate evidence of a significantly higher rate of tumor response to standard irinotsecan dosing.

Excerpt	Relevance	Reference
" 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)	0.78
" 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
" 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)	0.52
" 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)	0.56
" 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)	0.29
" 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)	0.49
" 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)	0.57
" 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
" 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)	0.55
"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)	0.55
" 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)	0.55
" 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)	0.54
" 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)	0.73
" 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)	0.3
" 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)	0.58
" 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)	0.56
" 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)	1.74
" 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)	0.91
" 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
" 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)	1.74
" 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)	0.82
" 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)	0.3
" 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)	0.3
" 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)	1.21
"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)	0.57
"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)	0.57
" 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)	0.58
" 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)	0.88
" 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)	0.58
" 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)	0.58
"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)	0.58
" 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
" 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)	0.72
" 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)	0.84
" 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)	0.79
" 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)	0.81
"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)	0.86
" 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)	0.58
"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)	0.58
"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)	0.58
"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)	0.31
"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)	0.84
" 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)	0.6
"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)	0.58
" 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)	0.76
" 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)	0.56
" 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)	1.76
" 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)	0.63
" 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)	1.76
"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)	0.61
" 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)	0.83
" 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
" 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)	0.75
" 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)	0.98
" 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)	0.89
" 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)	0.88
") 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
" 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)	0.58
" 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)	0.85
" 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, )	0.13
" 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)	2.01
" 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)	0.78
"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)	0.54
" 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)	0.53
"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)	0.85
" 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
" 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
" 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)	0.8
" 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)	0.57
" 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)	0.66
" 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
" 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)	0.85
" 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)	0.76
" 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)	0.64
" 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)	0.6
"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)	0.9
" 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)	1.77
" 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)	0.65
" 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)	0.79
" 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)	0.57
" 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)	0.56
" 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)	0.92
"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)	0.63
" 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)	0.81
" 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)	0.58
" 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)	0.58
" 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)	0.86
" 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)	0.82
"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)	0.88
" 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)	0.69
" 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)	1.77
" 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)	0.63
" 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)	0.59
" 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)	1.78
"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, )	1.79
" 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)	0.55
" 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)	0.68
" 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)	0.89
" 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)	1.24
"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, )	0.67
"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)	0.76
" 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, )	0.73
" 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)	1.56
" 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)	0.91
" 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)	0.8
" 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)	1.5
" 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)	0.58
" 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, )	0.6
" 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, )	0.36
" 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)	0.6
" 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)	0.76
" 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)	0.34
" 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)	0.75
" 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)	0.53
" 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)	0.57
" 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)	0.6
" 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)	1.26
" 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)	1.26
" 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)	0.77
" 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)	0.8
" 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)	2.7
" 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)	0.7
"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)	0.85
"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)	0.77
" 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)	0.77
" 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)	0.55
" 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)	0.82
" 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)	1.8
"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)	2.03
" 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)	0.69
" 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)	0.58
" 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
" 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)	0.88
" 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)	0.93
" 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)	0.85
"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)	0.88
"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)	0.61
"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)	0.8
" 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)	0.57
"Individualized drug dosing is a longstanding goal of clinical pharmacologists."	( Individualizing dosing of irinotecan. Innocenti, F; Ratain, MJ, 2010)	0.66
" 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)	0.83
"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, )	1.78
"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)	0.84
" 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)	0.63
"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)	0.61
" 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
" 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)	0.37
" 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)	0.61
"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)	0.89
" 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)	0.87
"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)	0.84
" 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)	0.92
" 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)	0.66
" 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)	1.62
" 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)	0.61
" The glycinamide analog 45 showed significant efficacy in the HCT-116 xenograft model, with 64% inhibition of tumor growth upon dosing at 20 mg/kg qd."	( 1,1-Diarylalkenes as anticancer agents: dual inhibitors of tubulin polymerization and phosphodiesterase 4. Cedzik, D; Chen, R; Collette, A; Leisten, J; Liu, W; Lu, L; Man, HW; Muller, GW; Narla, RK; Raymon, HK; Ruchelman, AL; Zhang, L, 2011)	0.37
" 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)	0.66
" 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)	0.61
" 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)	0.81
"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)	0.6
"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)	0.86
"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)	0.87
" 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
"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)	0.9
" 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)	0.83
" 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)	0.84
" 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)	0.87
" 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)	2.07
" 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)	0.74
"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)	0.78
"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)	0.63
" 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)	0.63
" 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)	0.6
" 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)	0.97
"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)	0.66
" 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)	0.75
" 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)	0.67
"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)	0.87
"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)	0.96
" 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)	1.23
"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)	0.88
"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
" 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)	0.63
" 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)	0.88
"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, )	0.42
" 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
" 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)	0.67
" 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)	0.89
" 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
" 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)	0.68
" 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)	0.86
" 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
"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)	1.11
" 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)	1.13
"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)	0.92
"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)	2.12
" 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)	0.67
" 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)	0.63
" 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)	0.65
" 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 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)	0.94
" 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 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)	0.87
"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)	0.9
"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)	0.67
"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)	0.46
"Gastrointestinal (GI) adverse events (AEs) are frequently dose limiting for oncology agents, requiring extensive clinical testing of alternative schedules to identify optimal dosing regimens."	( Systems Pharmacology Model of Gastrointestinal Damage Predicts Species Differences and Optimizes Clinical Dosing Schedules. Barnes, J; Cronin, A; Jasper, P; Mettetal, JT; Shankaran, H; Sharma, P; Tolsma, J, 2018)	0.48
" 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
" By analyzing multiple CTOs from a patient, this method could be used to predict patient-specific drug responses and help to improve personalized dosing regimens."	( MALDI Mass Spectrometry Imaging for Evaluation of Therapeutics in Colorectal Tumor Organoids. Flinders, C; Hummon, AB; Liu, X; Mumenthaler, SM, 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)	0.72
"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)	0.74
" 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
" 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)	0.72
"5 mmol/ml, 1 mmol/ml, 2 mmol /ml, 5 mmol/ml, and 10 mmol/ml irinotecan (CPT-11) were dosed in all colon cancer cell groups."	( KDM5c inhibits multidrug resistance of colon cancer cell line by down-regulating ABCC1. Cao, B; Guo, S; Li, Q; Lin, H; Wang, J; Yang, G; Yu, J, 2018)	0.72
" 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)	0.79
" As for the biomarkers, carcinoembryonic antigen and lactate dehydrogenase (LDH) smoothly declined immediately after the initial dosing in patients with a partial response or stable disease."	( Multicenter open-label randomized phase II study of second-line panitumumab and irinotecan with or without fluoropyrimidines in patients with KRAS wild-type metastatic colorectal cancer (PACIFIC study). Hirata, K; Hotta, Y; Imasato, M; Ishibashi, K; Iwamoto, S; Maeda, H; Makiyama, A; Mishima, H; Morita, S; Morita, Y; Munemoto, Y; Nagasaka, T; Nagata, N; Sakamoto, J; Takemoto, H; Tanaka, C; Toyofuku, A; Yoshida, Y, 2019)	0.74
" This translational toxicology model could be used for other antineoplastic drugs to simulate various clinical dosing scenarios before human studies and mitigate potential GI AEs."	( A Citrulline-Based Translational Population System Toxicology Model for Gastrointestinal-Related Adverse Events Associated With Anticancer Treatments. Abdul-Hadi, K; Brown, A; Guan, E; Wagoner, M; Yoneyama, T; Zhu, AZX, 2019)	0.51
" These data indicate that the use of modified dosing FOLFIRINOX in advanced PC pts older than 75 appears to maintain similar toxicity and efficacy when compared to younger pts."	( Modified FOLFIRINOX in pancreatic cancer patients Age 75 or older. Fogelman, DR; Hess, KR; Ho, L; Javle, MM; Mizrahi, JD; Overman, MJ; Pant, S; Raghav, KPS; Rogers, JE; Shroff, RT; Varadhachary, GR; Wolff, RA, 2020)	0.56
" Thereafter, salvage minimally invasive Ivor-Lewis esophagectomy and 2-field lymph node dissection was performed, followed by oral apatinib plus S-1 at the prior dosage for 6 months."	( S-1 plus apatinib followed by salvage esophagectomy for irinotecan-refractory small cell carcinoma of the esophagus: A case report and review of the literature. Gong, LB; Wu, W; Yu, GM; Zhang, C; Zhang, M, 2020)	0.8
" Demographics, clinical and dosing characteristics, and treatment outcomes were collected."	( Real-World Dosing Patterns and Outcomes of Patients With Metastatic Pancreatic Cancer Treated With a Liposomal Irinotecan Regimen in the United States. Ahn, D; Barzi, A; Bekaii-Saab, T; Corvino, FA; Mamlouk, K; Miksad, R; Pulgar, S; Surinach, A; Torres, AZ; Valderrama, A; Wang, S, 2020)	0.77
" Evaluation of pharmacogenomically dosed perioperative gFOLFIRINOX (fluorouracil, leucovorin, oxaliplatin, and UGT1A1 genotype-directed irinotecan) to optimize efficacy while limiting toxic effects may have value."	( Evaluation of the Association of Perioperative UGT1A1 Genotype-Dosed gFOLFIRINOX With Margin-Negative Resection Rates and Pathologic Response Grades Among Patients With Locally Advanced Gastroesophageal Adenocarcinoma: A Phase 2 Clinical Trial. Allen, K; Alpert, L; Catenacci, DVT; Chase, L; de Wilton Marsh, R; Ferguson, MK; Gordon, B; Hart, J; Karrison, T; Kindler, HL; Kipping-Johnson, K; Liao, CY; Lomnicki, S; Markevicius, U; Maron, SB; Moore, K; Narula, S; Peterson, B; Polite, BN; Posner, MC; Prachand, VN; Racette, C; Rampurwala, MM; Roggin, KK; Setia, N; Siddiqui, UD; Turaga, K; Xiao, SY, 2020)	0.76
"In this study, perioperative pharmacogenomically dosed gFOLFIRINOX was feasible, providing downstaging with PRG 1 in more than one-third of patients and an R0 resection rate in 92% of patients."	( Evaluation of the Association of Perioperative UGT1A1 Genotype-Dosed gFOLFIRINOX With Margin-Negative Resection Rates and Pathologic Response Grades Among Patients With Locally Advanced Gastroesophageal Adenocarcinoma: A Phase 2 Clinical Trial. Allen, K; Alpert, L; Catenacci, DVT; Chase, L; de Wilton Marsh, R; Ferguson, MK; Gordon, B; Hart, J; Karrison, T; Kindler, HL; Kipping-Johnson, K; Liao, CY; Lomnicki, S; Markevicius, U; Maron, SB; Moore, K; Narula, S; Peterson, B; Polite, BN; Posner, MC; Prachand, VN; Racette, C; Rampurwala, MM; Roggin, KK; Setia, N; Siddiqui, UD; Turaga, K; Xiao, SY, 2020)	0.56
"Temporal control of drug dosing is indispensable for a successful combination therapy that utilizes cisplatin (CDDP) and irinotecan (IRN), with clinical evidence supporting a higher response rate when CDDP was administered prior to IRN."	( Double-crosslinked nanocomposite hydrogels for temporal control of drug dosing in combination therapy. Liu, J; Tang, X; Wu, C; Xu, K; Yang, L; Zhai, Z; Zhao, L; Zhong, W, 2020)	0.77
" This pharmacokinetic/pharmacodynamic (PK/PD) study was performed to determine the effect of different G-CSF regimens on the incidence and duration of neutropenia following FOLFIRINOX administration in order to propose an optimal G-CSF dosing schedule."	( Impact of granulocyte colony-stimulating factor on FOLFIRINOX-induced neutropenia prevention: A population pharmacokinetic/pharmacodynamic approach. Bengrine-Lefevre, L; Ghiringhelli, F; Macaire, P; Paris, J; Schmitt, A; Vincent, J, 2020)	0.56
" Final model estimates were used to simulate different G-CSF dosing schedules for 1000 virtual subjects."	( Impact of granulocyte colony-stimulating factor on FOLFIRINOX-induced neutropenia prevention: A population pharmacokinetic/pharmacodynamic approach. Bengrine-Lefevre, L; Ghiringhelli, F; Macaire, P; Paris, J; Schmitt, A; Vincent, J, 2020)	0.56
" We aimed to improve FOLFOXIRI by optimization of the dosing and the sequence of drug administration."	( Drug-Drug Interactions of Irinotecan, 5-Fluorouracil, Folinic Acid and Oxaliplatin and Its Activity in Colorectal Carcinoma Treatment. Nowak-Sliwinska, P; Ramzy, GM; Rausch, M; Zoetemelk, M, 2020)	0.86
" Side effects associated with chemotherapy delays or modifications included thrombocytopenia (28%) and nausea/vomiting (19%), with temozolomide dosing most frequently modified."	( Children with DIPG and high-grade glioma treated with temozolomide, irinotecan, and bevacizumab: the Seattle Children's Hospital experience. Browd, SR; Cole, BL; Crotty, EE; Ellenbogen, RG; Ermoian, RP; Geyer, JR; Hauptman, JS; Leary, SES; Lee, A; Lockwood, CM; Millard, NE; Ojemann, JG; Olson, JM; Paulson, VA; Sato, AA; Vitanza, NA, 2020)	0.79
" Whereas reductions of NTx dosage was more common in elderly patients in comparison 1 (p = 0."	( Neoadjuvant therapy in elderly patients receiving FOLFIRINOX or gemcitabine/nab-paclitaxel for borderline resectable or locally advanced pancreatic cancer is feasible and lead to a similar oncological outcome compared to non-aged patients - Results of the Ceyhan, GO; Damm, M; Kordes, M; Maggino, L; Moir, J; Rosendahl, J; Schorn, S; Weniger, M, 2020)	0.56
" Dose reduction was defined as any decrease from initial dose; dose delay was any dosing delay >3 days from target date."	( Early dose reduction/delay and the efficacy of liposomal irinotecan with fluorouracil and leucovorin in metastatic pancreatic ductal adenocarcinoma (mPDAC): A post hoc analysis of NAPOLI-1. Bekaii-Saab, T; Belanger, B; Blanc, JF; Chen, LT; de Jong, FA; Macarulla, T; Mirakhur, B; Siveke, JT, 2021)	0.87
"Irinotecan is an anticancer drug for which significant benefits from personalised dosing are expected."	( A simple, rapid and low-cost spectrophotometric method for irinotecan quantification in human plasma and in pharmaceutical dosage forms. Argyropoulou, A; Gkotzamani, P; Karkalousos, P; Petro, V; Tsotsou, GE, 2021)	2.31
" A single dosage induced significant improvement of anti-tumour activity (over either the free drugs or the iTSL without FUS-activation) in triple negative breast cancer xenografts tumours in mice."	( Image-guided thermosensitive liposomes for focused ultrasound enhanced co-delivery of carboplatin and SN-38 against triple negative breast cancer in mice. Amrahli, M; Cressey, P; Gedroyc, W; So, PW; Thanou, M; Wright, M, 2021)	0.62
" The impact of proactive regulatory action, such as recommended dosing and therapeutic drug monitoring (TDM), was also observable within the global database."	( The Use of Subgroup Disproportionality Analyses to Explore the Sensitivity of a Global Database of Individual Case Safety Reports to Known Pharmacogenomic Risk Variants Common in Japan. Aoki, Y; Chandler, RE; Lönnstedt, IM; Wakao, R, 2021)	0.62
" Further approaches taken to improve the efficacy of 5-FU chemotherapy regimens have focused on optimising the route and dosing schedules and regulating folate metabolism."	( Metastatic colorectal cancer: Advances in the folate-fluoropyrimidine chemotherapy backbone. de Gramont, A; Glimelius, B; Marshall, J; Stintzing, S; Yoshino, T, 2021)	0.62
" Over the last 10 years, the pharmacokinetic and pharmacodynamic profile of panitumumab has been studied to further evaluate its safety, efficacy, and optimal dosing regimen."	( Panitumumab: A Review of Clinical Pharmacokinetic and Pharmacology Properties After Over a Decade of Experience in Patients with Solid Tumors. Dutta, S; Kast, J; Upreti, VV, 2021)	0.62
"Body surface area (BSA)-based dosing of irinotecan (IR) does not account for its pharmacokinetic (PK) and pharmacodynamic (PD) variabilities."	( Evaluation of pharmacogenomics and hepatic nuclear imaging-related covariates by population pharmacokinetic models of irinotecan and its metabolites. Beale, PJ; Burge, ME; Campbell, I; Crowley, S; Cullinane, C; Hatzimihalis, A; Hicks, RJ; Jefford, M; Karapetis, CS; Liauw, W; Link, E; Liu, Z; Martin, JH; Matera, A; McLachlan, SA; Michael, M; Price, T; Thompson, M, 2022)	1.2
"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)	1.06
" We provide an overview of current evidence and recommendations for individualized dosing of irinotecan in metastatic colorectal cancer patients."	( Elucidating the role of pharmacogenetics in irinotecan efficacy and adverse events in metastatic colorectal cancer patients. Páez, D; Riera, P, 2021)	1.1
" Guidelines recommend FP dosing adjusted to genotype-predicted DPD activity based on four DPYD variants (rs3918290, rs55886062, rs67376798 and rs56038477)."	( DPYD polymorphisms c.496A>G, c.2194G>A and c.85T>C and risk of severe adverse drug reactions in patients treated with fluoropyrimidine-based protocols. Bilić, I; Božina, N; Ganoci, L; Lešnjaković, L; Pleština, S; Šimičević, L; Trkulja, V, 2022)	0.72
" 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)	0.93
"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)	1.22
" 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)	1.21
"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)	1.21
" This translated to in vivo antitumor activity, with tumor control requiring continuous dosing and free plasma exposures, which correlated with induction of pCHK1, pRAD50, and γH2AX."	( ATR Inhibitor AZD6738 (Ceralasertib) Exerts Antitumor Activity as a Monotherapy and in Combination with Chemotherapy and the PARP Inhibitor Olaparib. Bargh-Dawson, H; Brown, E; Gerrard, J; Hughes, AM; Jones, GN; Lau, A; O'Connor, MJ; Odedra, R; Wallez, Y; Wijnhoven, PWG; Wilson, Z; Young, LA, 2022)	0.72
"Original FOLFIRINOX (oFFX) is more toxic than other regimens for patients with metastatic pancreatic cancer (mPC); therefore, a modified FFX (mFFX) regimen with a reduced dosage has been used in Japanese clinical practice."	( Multicenter Retrospective Analysis of Original versus Modified FOLFIRINOX in Metastatic Pancreatic Cancer: Results of the NAPOLEON Study. Arima, S; Fukahori, M; Honda, T; Ide, Y; Ido, A; Kawahira, M; Koga, F; Komori, A; Makiyama, A; Mitsugi, K; Mizuta, T; Nakazawa, J; Nio, K; Otsu, S; Otsuka, T; Shibuki, T; Shimokawa, M; Shirakawa, T; Taguchi, H; Tsuruta, N; Ueda, Y; Ureshino, N, 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)	1.12
" Pharmacokinetic-guided (PKG) dosing has demonstrated beneficial effects in other tumors, but scarce data is available in pancreatic cancer."	( Therapeutic drug monitoring of neoadjuvant mFOLFIRINOX in resected pancreatic ductal adenocarcinoma. Aldaz, A; Arbea, L; Chopitea, A; Martí-Cruchaga, P; Pardo, F; Ponz-Sarvise, M; Rodríguez-Rodríguez, J; Rotellar, F; Sala-Elarre, P; Subtil, JC; Urrizola, A; Vilalta-Lacarra, A; Zozaya, G, 2023)	0.91
" 5-Fluorouracil (5-FU) dosage was adjusted throughout neoadjuvant treatment according to pharmacokinetic parameters and Irinotecan (CPT-11) pharmacokinetic variables were retrospectively estimated."	( Therapeutic drug monitoring of neoadjuvant mFOLFIRINOX in resected pancreatic ductal adenocarcinoma. Aldaz, A; Arbea, L; Chopitea, A; Martí-Cruchaga, P; Pardo, F; Ponz-Sarvise, M; Rodríguez-Rodríguez, J; Rotellar, F; Sala-Elarre, P; Subtil, JC; Urrizola, A; Vilalta-Lacarra, A; Zozaya, G, 2023)	1.12
"In this phase Ib study MODURATE, we optimized the dosing schedule and tested the efficacy and safety of trifluridine/tipiracil, irinotecan, and bevacizumab in patients with metastatic colorectal cancer with fluoropyrimidine and oxaliplatin treatment failure."	( Bevacizumab, Irinotecan, and Biweekly Trifluridine/Tipiracil for Metastatic Colorectal Cancer: MODURATE, a Phase Ib Study. Ando, M; Hamauchi, S; Honda, K; Kadowaki, S; Kawakami, T; Masuishi, T; Mori, K; Muro, K; Narita, Y; Onozawa, Y; Shirasu, H; Taniguchi, H; Todaka, A; Tsushima, T; Yamazaki, K; Yasui, H; Yokota, T, 2023)	1.48
" The concomitant dosing schedule was discontinued because of dose-limiting toxicities in 2 of 2 patients treated."	( Regorafenib plus Vincristine and Irinotecan in Pediatric Patients with Recurrent/Refractory Solid Tumors: An Innovative Therapy for Children with Cancer Study. Bautista, F; Brennan, BJ; Campbell-Hewson, Q; Cañete Nieto, A; Casanova, M; Chung, JW; Corradini, N; Geoerger, B; Makin, G; Marshall, LV; Mueller, U; Ploeger, BA; Verschuur, AC; Zebger-Gong, H, 2023)	1.19