Phase II study of combined chemotherapy with irinotecan and S-1 (IRIS) plus bevacizumab in patients with inoperable recurrent or advanced colorectal cancer

Abstract

Background. In Japan, a study comparing the effectiveness and safety of irinotecan plus S-1 (IRIS) with those of a combination of 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) as second-line treatment in patients with advanced or recurrent colorectal cancer demonstrated that IRIS was non-inferior to FOLFIRI. We previously reported that IRIS is also effective as first-line treatment. Patients and Methods. Eligibility criteria included inoperable recurrent colorectal cancer with a confirmed diagnosis of adenocarcinoma, age ≥ 20 years, and no history of prior chemotherapy. S-1 (40-60 mg twice daily) was given orally on days 1 to 14, and irinotecan (100 mg/m2) and bevacizumab (5 mg/kg) were given intravenously on days 1 and 15 of a 28-day cycle. The primary endpoint was safety. The secondary endpoints included overall response (OR), progression-free survival (PFS), and overall survival (OS). Results. A total of 52 eligible patients were enrolled from October 2007 through March 2009. In safety analysis, the incidences of grade 3 or 4 adverse reactions were as follows: neutropenia, 27%; hypertension, 21%; and diarrhea, 17%. The overall response rate was 57.7%. Median progression-free survival was 16.7 months. Conclusion. IRIS plus bevacizumab is a well-tolerated, highly effective chemotherapeutic regimen that is easy to administer

A Phase II Trial of Combined Chemotherapy with Oral S-1 and 24-Hour Infusions of Irinotecan plus Bevacizumab in Patients with Metastatic Colorectal Cancer

“…In our study, the administered dose of irinotecan was lower. However, recent studies have reported good outcomes with oral S-1 and irinotecan plus bevacizumab, used instead of FOLFIRI plus bevacizumab, in patients with MCRC who had not previously received chemotherapy [30,31,32]. The effectiveness of combination chemotherapy with S-1, irinotecan, and bevacizumab in our study was consistent with the findings of previous studies.…”

“…In previous studies, irinotecan was administered in the following doses: 100 mg/m 2 biweekly by Komatsu et al [30], 80 mg/m 2 biweekly by Mizushima et al [32], and 150 mg/m 2 triweekly by Yamada et al [31]. In all of these studies, irinotecan was given as a 90-min infusion.…”

“…In all of these studies, irinotecan was given as a 90-min infusion. The administered doses of bevacizumab were as follows: 5 mg/m 2 biweekly by Komatsu et al [30], 7 mg/m 2 biweekly by Mizushima et al [32], and 7.5 mg/m 2 triweekly by Yamada et al [31]. The duration of the treatment cycles was 2 weeks in the study by Komatsu et al [30], 5 weeks in the study by Mizushima et al [32], and 3 weeks in the study by Yamada et al [31], and the response rates were 58, 47.4, and 67%, respectively.…”

“…The target number of patients was therefore set at 55, including dropouts and excluded patients [22,30,31]. Assuming that the lower threshold of the response rate was 10% in patients who had previously received chemotherapy (second line) and that the expected response rate was 30%, with an alpha value of 0.05 and a beta value of 0.2, we estimated the target number of previously untreated patients to be 19.…”

“…Combination chemotherapy with irinotecan, S-1, and bevacizumab has been reported to have a high response rate and good progression-free survival (PFS) in previously untreated patients with advanced colorectal cancer [30,31,32]. We now report the results of a phase II study of combined chemotherapy with oral S-1, irinotecan, given biweekly as a 24-hour continuous infusion, and bevacizumab in patients with previously treated or previously untreated MCRC.…”