Randomized multicenter Phase II trial of two different schedules of irinotecan combined with capecitabine as first‐line treatment in metastatic colorectal carcinoma

Abstract

BACKGROUND The aim of the current randomized Phase II study was to investigate the efficacy and safety of capecitabine combined with irinotecan as first‐line treatment in metastatic colorectal carcinoma (CRC). METHODS A total of 140 patients received capecitabine at a dose of 1250 mg/m2 twice daily on Days 2–15 and irinotecan at a dose of either 300 mg/m2 on Day 1 (Arm A) or 150 mg/m2 on Days 1 and 8 (Arm B) every 3 weeks. During the course of the study, enrollment was continued using lower doses of capecitabine (1000 mg/m2 twice daily) and irinotecan (Arm A: 240 mg/m2; Arm B: 120 mg/m2) to improve the safety profile of the combinations. RESULTS Efficacy was evaluable in 134 patients (68 in Arm A, 66 in Arm B). Objective responses were observed in 46% of the patients (8% complete response [CR]), including 47% in Arm A (9% CR; 38% partial response [PR]) and 44% in Arm B (8% CR; 36% PR). The median progression‐free survival was 8.3 months in Arm A and 7.6 months in Arm B. Among the first 52 patients treated with the higher doses, the most frequent Grade 3–4 adverse event was diarrhea (27%). The lower doses adopted in the subsequent 88 patients led to better diarrhea control, particularly in Arm A, and significant reductions in the incidence of all‐grade hand‐foot syndrome and abdominal pain. CONCLUSIONS The capecitabine and irinotecan combination was a highly active first‐line therapy in metastatic CRC. An acceptable safety profile was observed after dose reduction, particularly when irinotecan was administered on 1 day. Cancer 2004;100:279–87. © 2003 American Cancer Society.

A phase I and II study of 2-weekly irinotecan with capecitabine in advanced gastroesophageal adenocarcinoma

“…Published phase II studies of the irinotecan/capecitabine combination in colorectal cancer have reported similar frequencies and types of grade X3 toxicity, with diarrhoea being the commonest, occurring in around 20% of patients and grade X3 neutropenia, lethargy, nausea and anorexia in around 10 -20% (Bajetta et al, 2004;Borner et al, 2005). Recently, the EORTC 40015 phase III study, comparing 2-weekly irinotecan/LV5FU2 vs 3-weekly irinotecan/capecitabine (both arms7celecoxib) in advanced colorectal cancer, was stopped prematurely because of excessive toxicity (Kohne et al, 2005).…”

Phase II study of capecitabine and irinotecan combination chemotherapy in patients with advanced gastric cancer

“…Recently, in a randomised multicentre phase II trial (Bajetta et al, 2004) comparing two different schedules of irinotecan combined with capecitabine as the first-line treatment for metastatic colorectal cancer, diarrhoea, which occurred in 37.8% of the patients at a grade 3/4 intensity, was the main adverse effect of the arm B regimen (capecitabine 1000 mg m À2 twice daily on days 2 -15 and irinotecan 120 mg m À2 on days 1 and 8, every 21 days). However, in the present study, a reduced dose of irinotecan (100 mg m À2 on days 1 and 8) was administered to alleviate adverse effects, and grade 3/4 diarrhoea and neutropenia was only observed in 15 and 10% of the patients, respectively.…”

“…Although several studies have shown the efficacy and safety of capecitabine and irinotecan for advanced colorectal cancer (Tewes et al, 2003;Bajetta et al, 2004;Borner et al, 2005;Kim et al, 2005;Rea et al, 2005), no results have yet been reported for advanced gastric cancer. Accordingly, the current phase II study was conducted to evaluate the efficacy and safety of a combination regimen of capecitabine plus irinotecan in patients with advanced gastric cancer.…”

Xeliri Plus Bevacizumab Compared with Folfiri Plus Bevacizumab as First-Line Setting in Patients with Metastatic Colorectal Cancer: Experiences at Two-Institutions

“…Phase I/II studies of capecitabine combination with irinotecan (XELIRI) showed comparable response rates compared with 5-FULV-irinotecan combination (Bajetta et al, 2004;Borner et al, 2005;Rea et al, 2005). On the other hand, XELIRI has been related with response rates of 38-45% and a time-to-progression of about of 8 months with manageable side-effect profiles (Tewes et al, 2003;Bajetta et al, 2004;Cartwright et al, 2005).…”