A Phase II open-label study of capecitabine in combination with irinotecan as first-line treatment for metastatic colorectal cancer

Abstract

3658 Background: Capecitabine (C) and irinotecan (I) have demonstrated to be effective against colorectal cancer. They have different antitumor mechanisms yet no cross-resistance. In this multicenter phase II study, we sought to assess the efficacy and safety of CI in patients (pts) with metastatic colorectal cancer. Methods: Between July 2001 and September 2002, 50 pts were registered; 1 was ineligible (prior I). A total of 49 pts received C 1000 mg/m2 twice daily (2000 mg/m2 daily dose) Days 1–14 and I 240 mg/m2 on Day 1 of every 21-day cycle. At baseline, 88% were white and 57% were male; median age was 64.5 years (range, 25.8–84.5); ECOG performance status was 0–2. Results: 7 pts were non-evaluable (1 early death, 1 other disease, 2 refused treatment, and 3 had no tumor assessment). Responses for 42 evaluable pts were 1 CR (2%), 18 PR (43%), 20 SD (48%) and 2 PD (7%), for an overall response rate (CR+PR) of 45% with median duration of response of 5.7 months (range, 2.5–11.8). Median survival was 13.4 months (range, 1.15 –23.6) and median progression free survival was 6.7 months (range, 1.15 –17.5). At 1-year, the estimated survival was 52% and the PFS was 15%. Patients received a median of 6 cycles of treatment (range, 1–18). Causes of death; 19 PD, cardiopulmonary arrest, CVA, suicide, and treatment related sudden death (1 each). Grade 1–2 hand-foot syndrome occurred in 8 pts (16%). NCI Grade ≥ 3 drug-related toxicities: GI (31%), neutropenia (12%), dehydration (10%), anemia, fatigue and pain (6%, each), febrile neutropenia (4%), leukopenia, myelosuppression, thrombocytopenia and weight loss (2%, each). Conclusions: Capecitabine and irinotecan given in this schedule is an active combination for the treatment of first line metastatic colorectal cancer. Although there was significant toxicity with the regimen, toxicity was manageable with dose reduction or dose delay. This combination should be further investigated in phase III trials. Supported by Roche Laboratories, Inc., NJ, USA Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche