PURPOSE: 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). PATIENTS AND METHODS: All patients had metastatic CRC and a World Health Organization performance status of 0 or 1. CPT-11 was administered over a 90-minute infusion every 2 weeks at a range of dose levels (100, 120, 150, 180, 200, 220, and 260 mg/m(2)). LV5FU2 was started 1 hour after the end of the biweekly CPT-11 infusion and was also administered on day 2. RESULTS: Fifty-five patients were entered onto this trial; 549 cycles were administered. The MTD was not reached at 260 mg/m(2), and a dose level of 300 mg/m(2) was added. The MTD as defined in the protocol was not reached at this dose level either, but all patients had cycles delayed and/or required a dose reduction. This dose was deemed to be the MTD. To take into account both the toxicity of and compliance with the biweekly schedule, the recommended CPT-11 dose was established at 180 to 200 mg/m(2). Antitumor activity was observed at almost all dose levels, with an objective response rate of 22%. Median time to progression was 6.3 months and overall survival was 15 months. CONCLUSION: The biweekly CPT-11/LV5FU2 combination is feasible and safe, without overlapping toxicity. CPT-11 at 180 to 200 mg/m(2) in combination with LV5FU2 has been selected as the recommended dose for further studies.
PURPOSE: 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). PATIENTS AND METHODS: All patients had metastatic CRC and a World Health Organization performance status of 0 or 1. CPT-11 was administered over a 90-minute infusion every 2 weeks at a range of dose levels (100, 120, 150, 180, 200, 220, and 260 mg/m(2)). LV5FU2 was started 1 hour after the end of the biweekly CPT-11 infusion and was also administered on day 2. RESULTS: Fifty-five patients were entered onto this trial; 549 cycles were administered. The MTD was not reached at 260 mg/m(2), and a dose level of 300 mg/m(2) was added. The MTD as defined in the protocol was not reached at this dose level either, but all patients had cycles delayed and/or required a dose reduction. This dose was deemed to be the MTD. To take into account both the toxicity of and compliance with the biweekly schedule, the recommended CPT-11 dose was established at 180 to 200 mg/m(2). Antitumor activity was observed at almost all dose levels, with an objective response rate of 22%. Median time to progression was 6.3 months and overall survival was 15 months. CONCLUSION: The biweekly CPT-11/LV5FU2 combination is feasible and safe, without overlapping toxicity. CPT-11 at 180 to 200 mg/m(2) in combination with LV5FU2 has been selected as the recommended dose for further studies.
Authors: Giuseppe Toffoli; Manish R Sharma; Elena Marangon; Bianca Posocco; Elizabeth Gray; Quan Mai; Angela Buonadonna; Blase N Polite; Gianmaria Miolo; Gianna Tabaro; Federico Innocenti Journal: Clin Cancer Res Date: 2016-08-09 Impact factor: 12.531
Authors: Giuseppe Toffoli; Erika Cecchin; Giampiero Gasparini; Mario D'Andrea; Giuseppe Azzarello; Umberto Basso; Enrico Mini; Sergio Pessa; Elena De Mattia; Giovanni Lo Re; Angela Buonadonna; Stefania Nobili; Paolo De Paoli; Federico Innocenti Journal: J Clin Oncol Date: 2009-12-28 Impact factor: 44.544