Miyamoto Y, Tsuji A, Tanioka H, Maekawa S, Kawanaka H, Kitazono M, Oki E, Emi Y, Murakami H, Ogata Y, Saeki H, Shimokawa M, Natsugoe S, Akagi Y, Baba H, Maehara Y

BACKGROUND Combination chemotherapy with S-1 and irinotecan is one of the standard treatments for metastatic colorectal cancer (mCRC) in Japan. However, there are few alternative practical second-line therapies. We conducted a phase II trial to evaluate the efficacy and safety of the combination of S-1 and irinotecan plus bevacizumab as a second-line treatment for oxaliplatin-refractory mCRC.

METHODS Patients with mCRC who were previously treated with oxaliplatin-containing regimens were enrolled. Oral S-1 at a dose of 80 mg/m(2) was administered twice daily for 2 weeks, followed by a 1-week drug-free interval. Irinotecan at a dose of 150 mg/m(2) and bevacizumab at a dose of 7.5 mg/kg were administered on day 1. The primary endpoint was progression-free survival (PFS).

RESULTS Thirty-seven patients were enrolled, and 34 and 36 patients were assessed for response and safety, respectively. The overall response rate was 20.6 % (95 % confidence interval [CI] 8.7-37.9), and the disease control rate was 76.5 % (95 % CI 58.8-89.3). The median PFS was 5.6 months (95 % CI 3.8-7.0). The median overall survival was 16.4 months (95 % CI 8.1-20.0). The most common grade 3/4 adverse events included neutropenia (25.0 %), anorexia (22.2 %), anemia (16.7 %), and fatigue/malaise (16.7 %). The most common grade 3/4 adverse event of special interest for bevacizumab was hypertension (30.6 %). One treatment-related death caused by gastrointestinal bleeding occurred.

CONCLUSIONS The findings suggest that the combination of S-1 and irinotecan plus bevacizumab is effective and tolerable as second-line chemotherapy for patients with oxaliplatin-refractory mCRC.

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