PURPOSE: Adding leucovorin to fluorouracil is known to improve response rate and overall survival in first-line chemotherapy for metastatic colorectal cancer (mCRC). The present multicenter phase II study evaluated the efficacy and safety of S-1, oxaliplatin, oral leucovorin, and bevacizumab combination therapy (SOLA). METHODS: Patients with unresectable and untreated mCRC received S-1 (40-60 mg bid) plus leucovorin (25 mg bid) orally for 1 week, and oxaliplatin (85 mg/m(2)) and bevacizumab (5 mg/kg) intravenously on day 1, every 2 weeks. Efficacy endpoints, including the response rate (the primary endpoint) and progression-free survival, were assessed by an independent review committee. RESULTS: Of the 29 eligible patients, 25 patients (86%) had a partial response [95% confidence interval (CI) 68-96%] and the remaining four patients showed stable disease with a trend toward tumor shrinkage. The median progression-free survival was 15 months (95% CI 10-26 months). The median overall survival was not reached after a median follow-up time of 34 months. The 3-year survival rate was 54%. Curative resections of metastatic lesions were performed in eight patients (28%). Common grade 3 or 4 adverse events were neutropenia (20%), hypertension (23%), anorexia (20%), fatigue (17%), diarrhea (10%), and peripheral sensory neuropathy (53%). CONCLUSIONS: The SOLA therapy showed excellent efficacy and tolerable toxicities except for peripheral sensory neuropathy in patients with mCRC. Since oxaliplatin-induced neuropathy can be alleviated by modifying its administration, SOLA is a promising candidate regimen to be compared with FOLFOX plus bevacizumab in a future phase III trial. CLINICAL TRIAL NUMBER: JapicCTI-090881.
PURPOSE: Adding leucovorin to fluorouracil is known to improve response rate and overall survival in first-line chemotherapy for metastatic colorectal cancer (mCRC). The present multicenter phase II study evaluated the efficacy and safety of S-1, oxaliplatin, oral leucovorin, and bevacizumab combination therapy (SOLA). METHODS:Patients with unresectable and untreated mCRC received S-1 (40-60 mg bid) plus leucovorin (25 mg bid) orally for 1 week, and oxaliplatin (85 mg/m(2)) and bevacizumab (5 mg/kg) intravenously on day 1, every 2 weeks. Efficacy endpoints, including the response rate (the primary endpoint) and progression-free survival, were assessed by an independent review committee. RESULTS: Of the 29 eligible patients, 25 patients (86%) had a partial response [95% confidence interval (CI) 68-96%] and the remaining four patients showed stable disease with a trend toward tumor shrinkage. The median progression-free survival was 15 months (95% CI 10-26 months). The median overall survival was not reached after a median follow-up time of 34 months. The 3-year survival rate was 54%. Curative resections of metastatic lesions were performed in eight patients (28%). Common grade 3 or 4 adverse events were neutropenia (20%), hypertension (23%), anorexia (20%), fatigue (17%), diarrhea (10%), and peripheral sensory neuropathy (53%). CONCLUSIONS: The SOLA therapy showed excellent efficacy and tolerable toxicities except for peripheral sensory neuropathy in patients with mCRC. Since oxaliplatin-induced neuropathy can be alleviated by modifying its administration, SOLA is a promising candidate regimen to be compared with FOLFOX plus bevacizumab in a future phase III trial. CLINICAL TRIAL NUMBER: JapicCTI-090881.