temozolomide and Neuroblastoma studies

Neuroblastoma: A common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and characterized by diverse clinical behavior, ranging from spontaneous remission to rapid metastatic progression and death. This tumor is the most common intraabdominal malignancy of childhood, but it may also arise from thorax, neck, or rarely occur in the central nervous system. Histologic features include uniform round cells with hyperchromatic nuclei arranged in nests and separated by fibrovascular septa. Neuroblastomas may be associated with the opsoclonus-myoclonus syndrome. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2099-2101; Curr Opin Oncol 1998 Jan;10(1):43-51)

Research Excerpts

Excerpt	Relevance	Reference
"The combination of irinotecan, temozolomide, dintuximab, and granulocyte-macrophage colony-stimulating factor (I/T/DIN/GM-CSF) demonstrated activity in patients with relapsed/refractory neuroblastoma in the randomized Children's Oncology Group ANBL1221 trial."	9.34	Irinotecan, Temozolomide, and Dinutuximab With GM-CSF in Children With Refractory or Relapsed Neuroblastoma: A Report From the Children's Oncology Group. ( Asgharzadeh, S; Bagatell, R; Birstler, J; Diccianni, MB; Felder, M; Glade-Bender, J; Hank, JA; Katzenstein, H; London, WB; Maris, JM; Mody, R; Naranjo, A; Parisi, MT; Park, JR; Servaes, SE; Shulkin, BL; Sondel, PM; Yu, AL; Zhang, FF, 2020)
"The primary aim of this Phase I study was to determine the maximum tolerated dose (MTD) of TPI 287 and the safety and tolerability of TPI 287 alone and in combination with temozolomide (TMZ) in pediatric patients with refractory or recurrent neuroblastoma or medulloblastoma."	9.22	A Phase 1 Trial of TPI 287 as a Single Agent and in Combination With Temozolomide in Patients with Refractory or Recurrent Neuroblastoma or Medulloblastoma. ( Ashikaga, T; Bergendahl, G; DeSarno, M; Eslin, D; Ferguson, W; Hanna, GK; Higgins, T; Kaplan, J; Kraveka, J; Mitchell, D; Roberts, W; Sholler, GL; Werff, AV, 2016)
"To assess objective response rate (ORR) after two cycles of temozolomide in combination with topotecan (TOTEM) in children with refractory or relapsed neuroblastoma."	9.19	Phase II study of temozolomide in combination with topotecan (TOTEM) in relapsed or refractory neuroblastoma: a European Innovative Therapies for Children with Cancer-SIOP-European Neuroblastoma study. ( Aerts, I; Amoroso, L; Boubaker, A; Casanova, M; Chastagner, P; Courbon, F; Devos, A; Di Giannatale, A; Dias-Gastellier, N; Ducassoul, S; Geoerger, B; Landman-Parker, J; Le Deley, MC; Malekzadeh, K; Mc Hugh, K; Munzer, C; Riccardi, R; Rubie, H; Verschuur, A; Zwaan, CM, 2014)
"Patients with relapsed/refractory neuroblastoma measurable by cross-sectional imaging (stratum 1) or assessable by bone marrow aspirate/biopsy or metaiodobenzylguanidine (MIBG) scan (stratum 2) received irinotecan (10 mg/m(2)/dose 5 days a week for 2 weeks) and temozolomide (100 mg/m(2)/dose for 5 days) every 3 weeks."	9.15	Phase II study of irinotecan and temozolomide in children with relapsed or refractory neuroblastoma: a Children's Oncology Group study. ( Bagatell, R; Cohn, SL; Kretschmar, C; London, WB; Maris, JM; Stewart, CF; Voss, SD; Wagner, LM, 2011)
"Irinotecan and temozolomide have single-agent activity and schedule-dependent synergy against neuroblastoma."	9.14	Phase I trial of oral irinotecan and temozolomide for children with relapsed high-risk neuroblastoma: a new approach to neuroblastoma therapy consortium study. ( Crews, KR; Daldrup-Link, HE; Groshen, S; Hawkins, RA; Jackson, HA; Maris, JM; Matthay, KK; Park, JR; Reynolds, CP; Stewart, CF; Villablanca, JG; Wagner, LM, 2009)
"To determine the response rate (RR) of neuroblastoma (NB) in children to temozolomide (TMZ), and evaluate the duration of response and tolerance of the drug in this patient population."	9.12	Phase II study of temozolomide in relapsed or refractory high-risk neuroblastoma: a joint Société Française des Cancers de l'Enfant and United Kingdom Children Cancer Study Group-New Agents Group Study. ( Auvrignon, A; Baunin, C; Bergeron, C; Biassoni, L; Brisse, H; Chisholm, J; Coze, C; Defachelles, AS; Dickinson, F; Djafari, L; Giammarile, F; Hobson, R; McHugh, K; Morland, B; Mosseri, V; Munzer, C; Rubie, H; Valteau-Couanet, D; Vassal, G; Weston, C, 2006)
"Although chemoimmunotherapy is widely used for treatment of children with relapsed high-risk neuroblastoma (HRNB), little is known about timing, duration, and evolution of response after irinotecan/temozolomide/dinutuximab/granulocyte-macrophage colony-stimulating factor (I/T/DIN/GM-CSF) therapy."	8.31	Progression-Free Survival and Patterns of Response in Patients With Relapsed High-Risk Neuroblastoma Treated With Irinotecan/Temozolomide/Dinutuximab/Granulocyte-Macrophage Colony-Stimulating Factor. ( Bagatell, R; Carlowicz, C; Cash, T; Choe, M; Desai, AV; Federico, SM; Foster, JH; Granger, M; Lerman, BJ; Li, Y; Macy, ME; Mody, R; Morgenstern, DA; Pinto, N; Rafael, MS; Ranavaya, A; Sadanand, A; Shusterman, S; Somers, K; Streby, KA; Weiss, BD; Yazdani, S; Zeno, RN, 2023)
"Treatment of neuroblastoma tumor cells with cabozantinib inhibits RET and ERK phosphorylation and is effective against neuroblastoma tumor cell lines alone and in combination with 13-cis-retinoic acid, topotecan, and temozolomide."	7.81	Sensitivity of neuroblastoma to the novel kinase inhibitor cabozantinib is mediated by ERK inhibition. ( Scorsone, K; Woodfield, SE; Zage, PE; Zhang, L, 2015)
"Human neuroblastoma cells were incubated with midazolam alone, as a pretreatment prior to incubation with TMZ or a coincubation of both."	7.81	Pretreatment but not subsequent coincubation with midazolam reduces the cytotoxicity of temozolomide in neuroblastoma cells. ( Bauer, I; Braun, S; Pannen, B; Werdehausen, R, 2015)
"We report a retrospective study of a novel regimen for neuroblastoma (NB) resistant to standard induction or salvage chemotherapy which now routinely includes topotecan."	7.77	High-dose carboplatin-irinotecan-temozolomide: treatment option for neuroblastoma resistant to topotecan. ( Cheung, NK; Kramer, K; Kushner, BH; Modak, S, 2011)
"Our in vitro and in vivo findings suggest that irinotecan drives the activity of irinotecan and TMZ in recurrent neuroblastoma."	7.76	Activity of irinotecan and temozolomide in the presence of O6-methylguanine-DNA methyltransferase inhibition in neuroblastoma pre-clinical models. ( Cai, W; Cui, W; Harutyunyan, N; Ji, L; Keshelava, N; Maldonado, NV; Reynolds, CP; Sposto, R, 2010)
"We show that lestaurtinib can inhibit the growth of neuroblastoma both in vitro and in vivo and can substantially enhance the efficacy of conventional chemotherapy, presumably by inhibition of the Trk/brain-derived neurotrophic factor autocrine survival pathway."	7.76	Lestaurtinib enhances the antitumor efficacy of chemotherapy in murine xenograft models of neuroblastoma. ( Balamuth, N; Brodeur, GM; Evans, AE; Ho, R; Iyer, R; Maris, JM; Minturn, JE; Qi, X; Zhao, H, 2010)
") in combination with temozolomide and topotecan, against human neuroblastoma cells and xenografts, alongside associated pharmacologic and toxicologic indices."	7.75	Inhibition of poly(ADP-ribose) polymerase-1 enhances temozolomide and topotecan activity against childhood neuroblastoma. ( Boddy, AV; Castelbuono, DJ; Clifford, SC; Curtin, NJ; Daniel, RA; Drew, Y; Hostomsky, Z; Mulligan, EA; Plummer, ER; Rozanska, AL; Thomas, HD; Tweddle, DA, 2009)
"Although temozolomide has shown clinical activity against neuroblastoma, this activity is likely limited by the DNA repair enzyme O6-methylguanine DNA methyltransferase (MGMT)."	7.74	IFN-beta sensitizes neuroblastoma to the antitumor activity of temozolomide by modulating O6-methylguanine DNA methyltransferase expression. ( Davidoff, AM; Fan, M; McGee, MC; Nathwani, AC; Ng, CY; Nunnally, LC; Pfeffer, LM; Rosati, SF; Sims, TL; Stewart, CF; Tracey, L; Williams, RF; Zhou, J, 2008)
"The combination of temozolomide and irinotecan has preclinical schedule-dependent synergy against neuroblastoma but is not curative for relapsed high-risk patients."	7.74	Targeting methylguanine-DNA methyltransferase in the treatment of neuroblastoma. ( Billups, CA; Danks, MK; McLendon, RE; Wagner, LM; Weiss, BD; Yoon, KJ, 2007)
"To report on an irinotecan and temozolomide regimen for neuroblastoma (NB)."	7.73	Irinotecan plus temozolomide for relapsed or refractory neuroblastoma. ( Cheung, NK; Kramer, K; Kushner, BH; Modak, S, 2006)
" Pharmacokinetic testing did not show evidence of drug-drug interaction between irinotecan and alisertib."	6.82	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)
"Neuroblastoma is the most common tumour in children under 1 year old, accounting for 12-15% of childhood cancer deaths."	5.91	Autophagy Inhibition via Hydroxychloroquine or 3-Methyladenine Enhances Chemotherapy-Induced Apoptosis in Neuro-Blastoma and Glioblastoma. ( Balachandar, A; Bhagirath, E; Pandey, S; Vegh, C; Wear, D, 2023)
"Neuroblastoma is a malignant solid tumor that originates from the sympathetic nervous system in early childhood."	5.56	Selenium enhances TRPA1 channel-mediated activity of temozolomide in SH-SY5Y neuroblastoma cells. ( Övey, İS; Özkal, B, 2020)
" Overall, RO6839921 had a favourable pharmacokinetic profile consistent with intermittent dosing and was well tolerated alone and in combination."	5.51	Preclinical evaluation of the first intravenous small molecule MDM2 antagonist alone and in combination with temozolomide in neuroblastoma. ( Berry, P; Bonner, J; Chen, L; Daga, A; Kirk, C; Lunec, J; Newell, DR; Pastorino, F; Ponzoni, M; Thomas, HD; Tweddle, DA; Veal, GJ; Wood, KM; Zhao, Y, 2019)
"TMZ may be an effective agent for treatment of neuroblastoma as a single or in combination with other drugs."	5.42	Temozolomide may induce cell cycle arrest by interacting with URG4/URGCP in SH-SY5Y neuroblastoma cells. ( Avcı, ÇB; Çıtışlı, V; Dodurga, Y; Eroğlu, C; Şatıroğlu-Tufan, NL; Seçme, M, 2015)
"Renal failure is a rare complication of neuroblastoma or its therapy."	5.40	Irinotecan and temozolomide for treatment of neuroblastoma in a patient with renal failure on hemodialysis. ( Armstrong, AE; Cohn, RA; Dargart, J; Gosiengfiao, Y; Matossian, D; Reichek, J; Walterhouse, DO, 2014)
"Temozolomide is an attractive candidate treatment in neuroblastoma with methylated MGMT, especially in central nervous system relapsed cases."	5.39	Efficacy of temozolomide in a central nervous system relapse of neuroblastoma with O 6 -methylguanine methyltransferase (MGMT) promoter methylation. ( Marutsuka, K; Moritake, H; Nunoi, H; Shimonodan, H; Takeshima, H; Yamada, A; Yokogami, K, 2013)
" Our results demonstrate the potential of the anti-IGF-1R antibody alone and in combination with alkylating agents and support the therapeutic development of the AVE1642 for aggressive neuroblastoma."	5.36	Anti-insulin-like growth factor 1 receptor antibody EM164 (murine AVE1642) exhibits anti-tumour activity alone and in combination with temozolomide against neuroblastoma. ( Brasme, JF; Daudigeos-Dubus, E; Debussche, L; Geoerger, B; Opolon, P; Vassal, G; Venot, C; Vrignaud, P, 2010)
"Small recurrences confined to left supraclavicular nodes were treated with surgery alone at 4."	5.35	Recurrent metastatic neuroblastoma followed by myelodysplastic syndrome: possible leukemogenic role of temozolomide. ( Cheung, NK; Kramer, K; Kushner, BH; Laquaglia, MP; Modak, S, 2008)
"The primary aim of this Phase I study was to determine the maximum tolerated dose (MTD) of TPI 287 and the safety and tolerability of TPI 287 alone and in combination with temozolomide (TMZ) in pediatric patients with refractory or recurrent neuroblastoma or medulloblastoma."	5.22	A Phase 1 Trial of TPI 287 as a Single Agent and in Combination With Temozolomide in Patients with Refractory or Recurrent Neuroblastoma or Medulloblastoma. ( Ashikaga, T; Bergendahl, G; DeSarno, M; Eslin, D; Ferguson, W; Hanna, GK; Higgins, T; Kaplan, J; Kraveka, J; Mitchell, D; Roberts, W; Sholler, GL; Werff, AV, 2016)
"To assess objective response rate (ORR) after two cycles of temozolomide in combination with topotecan (TOTEM) in children with refractory or relapsed neuroblastoma."	5.19	Phase II study of temozolomide in combination with topotecan (TOTEM) in relapsed or refractory neuroblastoma: a European Innovative Therapies for Children with Cancer-SIOP-European Neuroblastoma study. ( Aerts, I; Amoroso, L; Boubaker, A; Casanova, M; Chastagner, P; Courbon, F; Devos, A; Di Giannatale, A; Dias-Gastellier, N; Ducassoul, S; Geoerger, B; Landman-Parker, J; Le Deley, MC; Malekzadeh, K; Mc Hugh, K; Munzer, C; Riccardi, R; Rubie, H; Verschuur, A; Zwaan, CM, 2014)
"Patients with relapsed/refractory neuroblastoma measurable by cross-sectional imaging (stratum 1) or assessable by bone marrow aspirate/biopsy or metaiodobenzylguanidine (MIBG) scan (stratum 2) received irinotecan (10 mg/m(2)/dose 5 days a week for 2 weeks) and temozolomide (100 mg/m(2)/dose for 5 days) every 3 weeks."	5.15	Phase II study of irinotecan and temozolomide in children with relapsed or refractory neuroblastoma: a Children's Oncology Group study. ( Bagatell, R; Cohn, SL; Kretschmar, C; London, WB; Maris, JM; Stewart, CF; Voss, SD; Wagner, LM, 2011)
"Irinotecan and temozolomide have single-agent activity and schedule-dependent synergy against neuroblastoma."	5.14	Phase I trial of oral irinotecan and temozolomide for children with relapsed high-risk neuroblastoma: a new approach to neuroblastoma therapy consortium study. ( Crews, KR; Daldrup-Link, HE; Groshen, S; Hawkins, RA; Jackson, HA; Maris, JM; Matthay, KK; Park, JR; Reynolds, CP; Stewart, CF; Villablanca, JG; Wagner, LM, 2009)
"To determine the response rate (RR) of neuroblastoma (NB) in children to temozolomide (TMZ), and evaluate the duration of response and tolerance of the drug in this patient population."	5.12	Phase II study of temozolomide in relapsed or refractory high-risk neuroblastoma: a joint Société Française des Cancers de l'Enfant and United Kingdom Children Cancer Study Group-New Agents Group Study. ( Auvrignon, A; Baunin, C; Bergeron, C; Biassoni, L; Brisse, H; Chisholm, J; Coze, C; Defachelles, AS; Dickinson, F; Djafari, L; Giammarile, F; Hobson, R; McHugh, K; Morland, B; Mosseri, V; Munzer, C; Rubie, H; Valteau-Couanet, D; Vassal, G; Weston, C, 2006)
"A meta-analysis of three phase II studies of children with relapsed/refractory neuroblastoma conducted in Europe (temozolomide, topotecan-vincristine-doxorubicin and topotecan-temozolomide) was performed."	4.95	Outcome of children with relapsed or refractory neuroblastoma: A meta-analysis of ITCC/SIOPEN European phase II clinical trials. ( Amoroso, L; Bautista, F; Chevance, A; Gambart, M; Garaventa, A; Geoerger, B; Le Deley, MC; Moreno, L; Paoletti, X; Pearson, AD; Rubie, H; Valteau-Couanet, D; Varo, A; Vassal, G, 2017)
"In heavily pretreated patients with refractory/relapsed solid tumors, the vincristine, irinotecan, and temozolomide regimen seemed promising in Ewing sarcoma patients and was well tolerated."	3.91	Vincristine, irinotecan, and temozolomide treatment for refractory/relapsed pediatric solid tumors: A single center experience. ( Büyükkapu Bay, S; Çakır, FB; Darendeliler, E; Görgün, O; Kebudi, R; Zülfikar, B, 2019)
"Treatment of neuroblastoma tumor cells with cabozantinib inhibits RET and ERK phosphorylation and is effective against neuroblastoma tumor cell lines alone and in combination with 13-cis-retinoic acid, topotecan, and temozolomide."	3.81	Sensitivity of neuroblastoma to the novel kinase inhibitor cabozantinib is mediated by ERK inhibition. ( Scorsone, K; Woodfield, SE; Zage, PE; Zhang, L, 2015)
"Human neuroblastoma cells were incubated with midazolam alone, as a pretreatment prior to incubation with TMZ or a coincubation of both."	3.81	Pretreatment but not subsequent coincubation with midazolam reduces the cytotoxicity of temozolomide in neuroblastoma cells. ( Bauer, I; Braun, S; Pannen, B; Werdehausen, R, 2015)
"We report a retrospective study of a novel regimen for neuroblastoma (NB) resistant to standard induction or salvage chemotherapy which now routinely includes topotecan."	3.77	High-dose carboplatin-irinotecan-temozolomide: treatment option for neuroblastoma resistant to topotecan. ( Cheung, NK; Kramer, K; Kushner, BH; Modak, S, 2011)
"Our in vitro and in vivo findings suggest that irinotecan drives the activity of irinotecan and TMZ in recurrent neuroblastoma."	3.76	Activity of irinotecan and temozolomide in the presence of O6-methylguanine-DNA methyltransferase inhibition in neuroblastoma pre-clinical models. ( Cai, W; Cui, W; Harutyunyan, N; Ji, L; Keshelava, N; Maldonado, NV; Reynolds, CP; Sposto, R, 2010)
"We show that lestaurtinib can inhibit the growth of neuroblastoma both in vitro and in vivo and can substantially enhance the efficacy of conventional chemotherapy, presumably by inhibition of the Trk/brain-derived neurotrophic factor autocrine survival pathway."	3.76	Lestaurtinib enhances the antitumor efficacy of chemotherapy in murine xenograft models of neuroblastoma. ( Balamuth, N; Brodeur, GM; Evans, AE; Ho, R; Iyer, R; Maris, JM; Minturn, JE; Qi, X; Zhao, H, 2010)
") in combination with temozolomide and topotecan, against human neuroblastoma cells and xenografts, alongside associated pharmacologic and toxicologic indices."	3.75	Inhibition of poly(ADP-ribose) polymerase-1 enhances temozolomide and topotecan activity against childhood neuroblastoma. ( Boddy, AV; Castelbuono, DJ; Clifford, SC; Curtin, NJ; Daniel, RA; Drew, Y; Hostomsky, Z; Mulligan, EA; Plummer, ER; Rozanska, AL; Thomas, HD; Tweddle, DA, 2009)
"Although temozolomide has shown clinical activity against neuroblastoma, this activity is likely limited by the DNA repair enzyme O6-methylguanine DNA methyltransferase (MGMT)."	3.74	IFN-beta sensitizes neuroblastoma to the antitumor activity of temozolomide by modulating O6-methylguanine DNA methyltransferase expression. ( Davidoff, AM; Fan, M; McGee, MC; Nathwani, AC; Ng, CY; Nunnally, LC; Pfeffer, LM; Rosati, SF; Sims, TL; Stewart, CF; Tracey, L; Williams, RF; Zhou, J, 2008)
"The combination of temozolomide and irinotecan has preclinical schedule-dependent synergy against neuroblastoma but is not curative for relapsed high-risk patients."	3.74	Targeting methylguanine-DNA methyltransferase in the treatment of neuroblastoma. ( Billups, CA; Danks, MK; McLendon, RE; Wagner, LM; Weiss, BD; Yoon, KJ, 2007)
"To report on an irinotecan and temozolomide regimen for neuroblastoma (NB)."	3.73	Irinotecan plus temozolomide for relapsed or refractory neuroblastoma. ( Cheung, NK; Kramer, K; Kushner, BH; Modak, S, 2006)
"The activity of temozolomide combined with irinotecan (CPT-11) was evaluated against eight independent xenografts (four neuroblastomas, three rhabdomyosarcomas, and one glioblastoma)."	3.70	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)
" Pharmacokinetic testing did not show evidence of drug-drug interaction between irinotecan and alisertib."	2.82	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)
" Pharmacokinetic studies and ERBB-receptor expression and signaling studies were performed."	2.73	Pediatric phase I and pharmacokinetic study of erlotinib followed by the combination of erlotinib and temozolomide: a Children's Oncology Group Phase I Consortium Study. ( Adamson, PC; Blaney, SM; Dancey, JE; Gilbertson, RJ; Hamilton, M; Ingle, AM; Jakacki, RI; Krailo, MD; Tersak, J; Voss, SD, 2008)
"Neuroblastoma is the most common tumour in children under 1 year old, accounting for 12-15% of childhood cancer deaths."	1.91	Autophagy Inhibition via Hydroxychloroquine or 3-Methyladenine Enhances Chemotherapy-Induced Apoptosis in Neuro-Blastoma and Glioblastoma. ( Balachandar, A; Bhagirath, E; Pandey, S; Vegh, C; Wear, D, 2023)
" Overall, RO6839921 had a favourable pharmacokinetic profile consistent with intermittent dosing and was well tolerated alone and in combination."	1.51	Preclinical evaluation of the first intravenous small molecule MDM2 antagonist alone and in combination with temozolomide in neuroblastoma. ( Berry, P; Bonner, J; Chen, L; Daga, A; Kirk, C; Lunec, J; Newell, DR; Pastorino, F; Ponzoni, M; Thomas, HD; Tweddle, DA; Veal, GJ; Wood, KM; Zhao, Y, 2019)
"TMZ may be an effective agent for treatment of neuroblastoma as a single or in combination with other drugs."	1.42	Temozolomide may induce cell cycle arrest by interacting with URG4/URGCP in SH-SY5Y neuroblastoma cells. ( Avcı, ÇB; Çıtışlı, V; Dodurga, Y; Eroğlu, C; Şatıroğlu-Tufan, NL; Seçme, M, 2015)
"Renal failure is a rare complication of neuroblastoma or its therapy."	1.40	Irinotecan and temozolomide for treatment of neuroblastoma in a patient with renal failure on hemodialysis. ( Armstrong, AE; Cohn, RA; Dargart, J; Gosiengfiao, Y; Matossian, D; Reichek, J; Walterhouse, DO, 2014)
" 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."	1.39	5-day/5-drug myeloablative outpatient regimen for resistant neuroblastoma. ( Basu, EM; Cheung, NK; Kramer, K; Kushner, BH; Modak, S; Roberts, SS, 2013)
"Temozolomide is an attractive candidate treatment in neuroblastoma with methylated MGMT, especially in central nervous system relapsed cases."	1.39	Efficacy of temozolomide in a central nervous system relapse of neuroblastoma with O 6 -methylguanine methyltransferase (MGMT) promoter methylation. ( Marutsuka, K; Moritake, H; Nunoi, H; Shimonodan, H; Takeshima, H; Yamada, A; Yokogami, K, 2013)
"Neuroblastoma is a common pediatric tumor characterized by clinical heterogeneity."	1.38	AZ64 inhibits TrkB and enhances the efficacy of chemotherapy and local radiation in neuroblastoma xenografts. ( Brodeur, GM; Brown, JL; Evans, AE; Ho, R; Iyer, R; Light, JE; Minturn, JE; Simpson, AM; Thress, K; Varela, CR; Zhao, H, 2012)
" Our results demonstrate the potential of the anti-IGF-1R antibody alone and in combination with alkylating agents and support the therapeutic development of the AVE1642 for aggressive neuroblastoma."	1.36	Anti-insulin-like growth factor 1 receptor antibody EM164 (murine AVE1642) exhibits anti-tumour activity alone and in combination with temozolomide against neuroblastoma. ( Brasme, JF; Daudigeos-Dubus, E; Debussche, L; Geoerger, B; Opolon, P; Vassal, G; Venot, C; Vrignaud, P, 2010)
"Small recurrences confined to left supraclavicular nodes were treated with surgery alone at 4."	1.35	Recurrent metastatic neuroblastoma followed by myelodysplastic syndrome: possible leukemogenic role of temozolomide. ( Cheung, NK; Kramer, K; Kushner, BH; Laquaglia, MP; Modak, S, 2008)
"Temozolomide was administered p."	1.31	Biochemical correlates of temozolomide sensitivity in pediatric solid tumor xenograft models. ( Brent, TP; Friedman, HS; Houghton, PJ; Kirstein, MN; Middlemas, DS; Poquette, C; Stewart, CF, 2000)

Research

Studies (52)

Authors

Clinical Trials (8)

Trial Overview

Trial Outcomes

Percentage of Patients in the Dinutuximab Arm Who Are Responders

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	14 (26.92)	29.6817
2010's	25 (48.08)	24.3611
2020's	13 (25.00)	2.80

Authors	Studies
Król, SK	1
Bębenek, E	1
Dmoszyńska-Graniczka, M	1
Sławińska-Brych, A	1
Boryczka, S	1
Stepulak, A	1
Castañeda, A	1
Gorostegui, M	1
Miralles, SL	1
Chamizo, A	1
Patiño, SC	1
Flores, MA	1
Garraus, M	1
Lazaro, JJ	1
Santa-Maria, V	1
Varo, A	2
Muñoz, JP	1
Mora, J	1
Olsen, TK	1
Dyberg, C	2
Embaie, BT	1
Alchahin, A	1
Milosevic, J	2
Ding, J	1
Otte, J	1
Tümmler, C	1
Hed Myrberg, I	1
Westerhout, EM	1
Koster, J	1
Versteeg, R	1
Ding, HF	1
Kogner, P	2
Johnsen, JI	2
Sykes, DB	1
Baryawno, N	2
Lerman, BJ	1
Li, Y	1
Carlowicz, C	1
Granger, M	1
Cash, T	1
Sadanand, A	1
Somers, K	1
Ranavaya, A	1
Weiss, BD	2
Choe, M	1
Foster, JH	1
Pinto, N	1
Morgenstern, DA	1
Rafael, MS	1
Streby, KA	1
Zeno, RN	1
Mody, R	2
Yazdani, S	1
Desai, AV	1
Macy, ME	1
Shusterman, S	1
Federico, SM	1
Bagatell, R	4
Kobushi, H	1
Saida, S	1
Umeda, K	1
Iwai, A	1
Kozuki, K	1
Kubota, H	1
Tanaka, K	1
Obu, S	1
Uchihara, Y	1
Tasaka, K	1
Kato, I	1
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Trial	Phase	Enrollment	Study Type	Start Date	Status
RAPID Feasibility Study: A Pilot Study for the Rapid Infusion of Dinutuximab[NCT05421897]	Phase 4	11 participants (Anticipated)	Interventional	2022-10-24	Recruiting
A Phase II Randomized Trial of Irinotecan/Temozolomide With Temsirolimus (NSC# 683864) or Chimeric 14.18 Antibody (Ch14.18) (NSC# 764038) in Children With Refractory, Relapsed or Progressive Neuroblastoma[NCT01767194]	Phase 2	73 participants (Actual)	Interventional	2013-02-12	Completed
A Phase I Study Of Oral Irinotecan, Temozolomide, Cefixime In Children With Recurrent/Resistant High-Risk Neuroblastoma[NCT00093353]	Phase 1	30 participants (Anticipated)	Interventional	2004-05-31	Completed
A Phase II Study of Irinotecan + Temozolomide in Children With Recurrent Neuroblastoma[NCT00311584]	Phase 2	59 participants (Actual)	Interventional	2006-04-30	Completed
Phase II Study of Temozolomide (Temodal) in Children Over 1 Year of Age With Relapsed or Refractory High Risk Neuroblastoma[NCT00276679]	Phase 2	0 participants	Interventional	2003-04-30	Completed
A Pilot Study Investigating Neoadjuvant Temozolomide-based Proton Chemoradiotherapy for High-Risk Soft Tissue Sarcomas[NCT00881595]	Phase 2	0 participants (Actual)	Interventional	2009-02-28	Withdrawn (stopped due to No patients accrued since study opened)
Phase 1b Trial of 5-fluorouracil, Leucovorin, Irinotecan in Combination With Temozolomide (FLIRT) and Bevacizumab for the First-line Treatment of Patients With MGMT Silenced, Microsatellite Stable Metastatic Colorectal Cancer.[NCT04689347]	Phase 1	18 participants (Anticipated)	Interventional	2021-01-01	Recruiting
Temozolomide and Irinotecan Consolidation in Patients With MGMT Silenced, Microsatellite Stable Colorectal Cancer With Persistence of Minimal Residual Disease in Liquid Biopsy After Standard Adjuvant Chemotherapy: the ERASE-TMZ Study[NCT05031975]	Phase 2	35 participants (Anticipated)	Interventional	2022-05-02	Recruiting
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Percentage of patients who are responders to therapy with dinutuximab will be tabulated, including a 95% confidence interval on the response rate. Responders are defined as patients who achieve a best overall response of complete response (CR), very good partial response (VGPR), or partial response (PR) per the International Neuroblastoma Response Criteria (INRC). Per INRC: CR= Disappearance of all target lesions. No evidence of tumor at any site; VGPR= >90% decrease of disease measurement for CT/MRI target lesions. All pre-existing bone lesions with CR by MIBG; MIBG scan can be stable disease (SD) or CR in soft tissue lesions corresponding to lesions on CT/MRI. CR in bone marrow. No new sites of tumor; PR= ≥30% decrease in disease measurement for CT/MRI target lesions. Bone marrow with CR. MIBG with either PR/CR in bone lesions; MIBG may be SD or CR in soft tissue lesions corresponding to lesions on CT/MRI. Homovanillic acid (HVA)/ Vanillylmandelic acid (VMA) may still be elevated. (NCT01767194)
Timeframe: Up to the first 6 cycles of treatment

Percentage of Randomized Patients Who Are Responders

Intervention	Percentage of patients (Number)
Arm II (Temozolomide, Irinotecan Hydrochloride, Dinutuximab)	41.2

The percentage of patients who are responders will be tabulated, including a 95% confidence interval on the response rate. Responders are defined as patients who achieve a best overall response of complete response (CR), very good partial response (VGPR), or partial response (PR) per the International Neuroblastoma Response Criteria (INRC). Per INRC: CR= Disappearance of all target lesions. No evidence of tumor at any site; VGPR= >90% decrease of the disease measurement for CT/MRI target lesions. All pre-existing bone lesions with CR by MIBG; MIBG scan can be stable disease (SD) or CR in soft tissue lesions corresponding to lesions on CT/MRI. CR in bone marrow. No new sites of tumor; PR= >=30% decrease in the disease measurement for CT/MRI target lesions. Bone marrow with CR. MIBG with either PR/CR in bone lesions; MIBG may be SD or CR in soft tissue lesions corresponding to lesions on CT/MRI. Homovanillic acid (HVA)/Vanillylmandelic acid (VMA) may still be elevated. (NCT01767194)
Timeframe: Up to the first 6 cycles of treatment

Overall Response - Complete Response (CR), Very Good Partial Response (VGPR) and Partial Response (PR)

Intervention	Percentage of patients (Number)
Arm I (Temozolomide, Irinotecan Hydrochloride, Temsirolimus)	5.6
Arm II (Temozolomide, Irinotecan Hydrochloride, Dinutuximab)	52.9

"The patient's best overall response obtained during Reporting Periods 1 and 2 will be scored as best response. Patients enrolled on Stratum 1 with bone marrow disease, a responder has no tumor cells detectable by routine morphology on 2 subsequent bilateral bone marrow aspirates and biopsies done at least 3 weeks apart. For patients enrolled on stratum 1 with MIBG only disease, response will be assessed using the Curie scale. Patients who have complete resolution of all MIBG positive lesions (CR) or resolution of at least one MIBG positive lesion with persistence of other lesions (PR) will be considered responders. For Stratum 2 a responder is defined to be a patient who achieves a best overall response of CR, VGPR or PR from CT/MRI scans from central review using (RECIST) Response Evaluation Criteria in Solid Tumor. A responder is defined to be a patient who achieves a best overall response of CR (Complete Response), VGPR (Very Good Partial Response) or PR (Partial Response)." (NCT00311584)
Timeframe: up to 6 courses of therapy, or about 6 months

Intervention	participants (Number)
Disease Eval by Bone Marrow or MIBG (Irinotecan/Temozolomide)	5
Disease Measurable by CT or MRI Scan (Irinotecan/Temozolomide)	3

temozolomide and Neuroblastoma