Yuji Miyamoto1, Akihito Tsuji2, Hiroaki Tanioka3, Soichiro Maekawa4, Hirofumi Kawanaka5,6, Masaki Kitazono7, Eiji Oki8, Yasunori Emi9, Hidetsugu Murakami10, Yutaka Ogata11, Hiroshi Saeki7, Mototsugu Shimokawa12, Shoji Natsugoe13, Yoshito Akagi10, Hideo Baba14, Yoshihiko Maehara8. 1. Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan. 2. Department of Clinical Oncology, Faculty of Medicine, Kagawa University, Kagawa, Japan. 3. Department of Medical Oncology, Okayama Rousai Hospital, Okayama, Japan. 4. Department of Surgery, Munakata Medical Association Hospital, Fukuoka, Japan. 5. National Hospital Organization, Beppu Medical Center, Beppu, Japan. 6. Clinical Research Institute and Department of Surgery, Oita, Japan. 7. Gastroenterological Surgery, Nanpuh Hospital, Kagoshima, Japan. 8. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 9. Department of Surgery, Saiseikai Fukuoka General Hospital, Fukuoka, Japan. 10. Department of Surgery, Kurume University School of Medicine, Kurume, Japan. 11. Department of Surgery, Kurume University Medical Center, Kurume, Japan. 12. Department of Cancer Information Research, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan. 13. Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan. 14. Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan. hdobaba@kumamoto-u.ac.jp.
Abstract
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 40 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.
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 40 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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