BACKGROUND: We conducted a dose escalation study combining cisplatin, irinotecan, and capecitabine (CIC), aiming to establish the maximum tolerated doses (MTD), side effect profile, and dose-limiting toxicity (DLT) of this novel regimen. PATIENTS AND METHODS: Intravenous cisplatin and irinotecan were to be administered on days 1 and 8, and oral capecitabine on days 1-14 of a 3-week cycle. The study was conducted in three parts. Part A: escalating doses of irinotecan (40 --> 80 mg/m2) and capecitabine (1000 --> 3300 mg/d) combined with a fixed dose of cisplatin (30 mg/m2). Part B: escalating doses of irinotecan (MTD-A --> MTD-A + 40 mg/m2) with fixed doses of cisplatin (20 mg/m2) and capecitabine (MTD-A level). Part C: escalating doses of capecitabine (1300 mg/d-->2600 mg/d) with fixed doses of cisplatin (20 mg/m2) and irinotecan (60 mg/m2). RESULTS: Of 51 eligible patients 27 (53%) were male, median age was 58 years and 88% had PS 0-1. Major primary disease sites were colorectal (24%), unknown (14%), stomach (14%), and pancreas (12%). MTD-A was cisplatin 30 mg/m2, irinotecan 60 mg/m2, capecitabine 1000 mg/d and MTD-B was cisplatin 20 mg/m2, irinotecan 90 mg/m2, capecitabine 1000 mg/d. An MTD was not formally established for part C. DLTs consisted of infection with neutropenia (1), diarrhea and fatigue (1), hypokalemia (1), diarrhea and febrile neutropenia (1) and C2 delay of > or = 2 weeks or 25% dose reduction in C1 due to neutropenia or thrombocytopenia (6). Seven patients had a partial response to treatment (four colorectal, one SCLC, one NSCLC, one unknown primary), twenty seven SD (53%), twelve PD (24%) and five NE (10%). CONCLUSION: CIC was associated with moderate toxicity and only modest antitumor activity. We conclude that this regimen has insufficient activity to justify further study in the phase II setting.
BACKGROUND: We conducted a dose escalation study combining cisplatin, irinotecan, and capecitabine (CIC), aiming to establish the maximum tolerated doses (MTD), side effect profile, and dose-limiting toxicity (DLT) of this novel regimen. PATIENTS AND METHODS: Intravenous cisplatin and irinotecan were to be administered on days 1 and 8, and oral capecitabine on days 1-14 of a 3-week cycle. The study was conducted in three parts. Part A: escalating doses of irinotecan (40 --> 80 mg/m2) and capecitabine (1000 --> 3300 mg/d) combined with a fixed dose of cisplatin (30 mg/m2). Part B: escalating doses of irinotecan (MTD-A --> MTD-A + 40 mg/m2) with fixed doses of cisplatin (20 mg/m2) and capecitabine (MTD-A level). Part C: escalating doses of capecitabine (1300 mg/d-->2600 mg/d) with fixed doses of cisplatin (20 mg/m2) and irinotecan (60 mg/m2). RESULTS: Of 51 eligible patients 27 (53%) were male, median age was 58 years and 88% had PS 0-1. Major primary disease sites were colorectal (24%), unknown (14%), stomach (14%), and pancreas (12%). MTD-A was cisplatin 30 mg/m2, irinotecan 60 mg/m2, capecitabine 1000 mg/d and MTD-B was cisplatin 20 mg/m2, irinotecan 90 mg/m2, capecitabine 1000 mg/d. An MTD was not formally established for part C. DLTs consisted of infection with neutropenia (1), diarrhea and fatigue (1), hypokalemia (1), diarrhea and febrile neutropenia (1) and C2 delay of > or = 2 weeks or 25% dose reduction in C1 due to neutropenia or thrombocytopenia (6). Seven patients had a partial response to treatment (four colorectal, one SCLC, one NSCLC, one unknown primary), twenty seven SD (53%), twelve PD (24%) and five NE (10%). CONCLUSION:CIC was associated with moderate toxicity and only modest antitumor activity. We conclude that this regimen has insufficient activity to justify further study in the phase II setting.
Authors: E Van Cutsem; C Twelves; J Cassidy; D Allman; E Bajetta; M Boyer; R Bugat; M Findlay; S Frings; M Jahn; J McKendrick; B Osterwalder; G Perez-Manga; R Rosso; P Rougier; W H Schmiegel; J F Seitz; P Thompson; J M Vieitez; C Weitzel; P Harper Journal: J Clin Oncol Date: 2001-11-01 Impact factor: 44.544
Authors: T Nakano; A P Chahinian; M Shinjo; N Togawa; A Tonomura; M Miyake; K Ninomiya; T Yamamoto; K Higashino Journal: Cancer Date: 1999-06-01 Impact factor: 6.860
Authors: E Van Cutsem; M Findlay; B Osterwalder; W Kocha; D Dalley; R Pazdur; J Cassidy; L Dirix; C Twelves; D Allman; J F Seitz; J Schölmerich; H U Burger; J Verweij Journal: J Clin Oncol Date: 2000-03 Impact factor: 44.544
Authors: R F DeVore; D H Johnson; J Crawford; J Garst; I W Dimery; J Eckardt; S G Eckhardt; G L Elfring; L J Schaaf; C K Hanover; L L Miller Journal: J Clin Oncol Date: 1999-09 Impact factor: 44.544
Authors: P Piedbois; P Rougier; M Buyse; J Pignon; L Ryan; R Hansen; B Zee; B Weinerman; J Pater; C Leichman; J Macdonald; J Benedetti; J Lokich; J Fryer; G Brufman; R Isacson; A Laplanche; E Levy Journal: J Clin Oncol Date: 1998-01 Impact factor: 44.544
Authors: V Vinciguerra; T J Degnan; A Sciortino; M O'Connell; T Moore; R Brody; D Budman; M Eng; D Carlton Journal: J Clin Oncol Date: 1986-10 Impact factor: 44.544