A phase II study of S-1, oxaliplatin, oral leucovorin, and bevacizumab combination therapy (SOLA) in patients with unresectable metastatic colorectal cancer

作者：Nishina Tomohiro^*; Kato Takeshi; Yamazaki Kentaro; Yoshino Takayuki; Miyata Yoshinori; Esaki Taito; Moriwaki Toshikazu; Boku Narikazu; Hyodo Ichinosuke

来源：Cancer Chemotherapy and Pharmacology, 2015, 76(3): 547-553.

DOI：10.1007/s00280-015-2825-5

• S-1
• Leucovorin
• Oxaliplatin
• SOLA
• Colorectal cancer
• Bevacizumab

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).
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.
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 %).
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.
JapicCTI-090881.

• 出版日期2015-9