Capecitabine (X) plus irinotecan (XELIRI) as first-line treatment for metastatic colorectal cancer (MCRC): Final safety findings from a phase II trial

Abstract

3602 Background: The oral fluoropyrimidine X (Xeloda) has superior efficacy and improved safety compared to 5-FU/LV in MCRC. Twice-daily oral X mimics 5-FU infusion and is replacing 5-FU in combination regimens. The efficacy and safety of X plus weekly irinotecan (XELIRI) were evaluated in first-line MCRC. Methods: Recommended doses from two independent phase I trials were: irinotecan 250 mg/m2 i.v. on day 1 plus capecitabine 1000 mg/m2 orally twice-daily on days 1–15, every 3 weeks. Patients (pts) ≥65 years received lower doses of both agents (200 mg/m2 i.v. on day 1 and 750 mg/m2 twice-daily on days 1–15, respectively). Results: Baseline characteristics of the 52 pts enrolled between Oct 2001 and Aug 2003: 29 men, 23 women; median Karnofsky PS 90 (70–100); median age 57.5 (30–79); colon cancer (85%), rectal cancer (11%), both (4%). Tumor differentiation was 15% poor, 63% moderate, 12% well, and 10% unknown. Most common metastatic sites were the liver (77%), lymph nodes (58%), and lung (33%), with 69% of pts having stage IV disease at initial diagnosis. Eleven pts (22%) had received prior adjuvant 5-FU. The median number of treatment cycles is currently 6 (maximum 12 cycles allowed). In the 51 patients evaluable for safety, the most common (>5%) treatment-related grade 3 adverse events were diarrhea (20%), vomiting (16%), dehydration (8%, 1 patient grade 4), nausea (6%), and HFS (6%). Grade 3/4 neutropenia was seen in 26% of pts. There were no treatment-related deaths. Twenty-seven of 44 evaluable pts (61%) showed a response to treatment (1 unconfirmed) and disease control (CR+PR+SD) was achieved in 37 pts (84%). Median time to progression (TTP) and overall survival are currently 6.1 months and 15.6 months, respectively. Conclusions: XELIRI is a highly active and well-tolerated first-line therapy for MCRC. Efficacy compares favorably with previous studies of infusional 5-FU/LV/irinotecan, and safety of XELIRI is comparable to that of FOLFIRI and IFL regimens. Capecitabine should replace 5-FU in combination with irinotecan to create an effective, safe, and convenient treatment option in first-line MCRC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Hoffmann-La Roche; Novartis Hoffmann-La Roche Hoffmann-La Roche; Lilly; Pfizer; Novartis