A multicenter phase II study of the stop-and-go modified FOLFOX6 with bevacizumab for first-line treatment of patients with metastatic colorectal cancer
Currently, no prospective data exists to support a “stop-and-go” modified FOLFOX6 regimen with bevacizumab in metastatic colorectal cancer (mCRC) patients. This study aimed to evaluate the efficacy and safety of this regimen in first-line mCRC patients. Eligible patients (age ≥20 years) had previously untreated mCRC; Eastern Cooperative Oncology Group performance status of 0–2; and adequate hematologic, hepatic, and renal function. The modified FOLFOX6 regimen and bevacizumab (5 mg/kg) was administered intravenously every 2 weeks. After 8 cycles, patients received maintenance therapy with simplified LV5FU2 and bevacizumab until completion of 8 cycles or disease progression. After maintenance therapy, patients received another 8 cycles of modified FOLFOX6 with bevacizumab until completion of 8 cycles or disease progression. We recruited 50 patients between August 2007 and January 2009. The overall response rate was 48% (80% confidence interval [CI]; 38.2–58) with outcomes as follows: complete response, n = 1; partial response, n = 23; stable disease, n = 21; progression, n = 1; and not evaluated, n = 4. Median time to treatment failure was 7.7 months (80% CI: 6.2–8.0), and median progression-free survival was 12.8 months (80% CI: 10.8–14). Grade 3/4 toxicities included neutropenia (40%), nausea (4%), diarrhea (14%), thrombosis (4%), and hypertension (4%) et al. Grade 1, 2, or 3 peripheral neuropathy was reported in 38%, 40%, and 10% of patients, respectively. The stop-and-go modified FOLFOX6 and bevacizumab regimen is effective and well tolerated as first-line chemotherapy for mCRC patients.
KeywordsMetastatic colorectal cancer Stop and go Modified FOLFOX6 Bevacizumab
We thank Hiroshi Yoshida, Aasako Sakamoto and Makiko Shinogi for data collection, and Yushi Nagai and Michiyo Tada for data management. This work was supported by Grants-in-Aid for Cancer Research from the Ministry of Health, Labour and Welfare of Japan [grant number 20S-3].
Conflict of interest statements
The authors declare that they have no conflict of interest.
- 2.Giantonio BJ, Catalano PJ, Meropol NJ et al (2007) Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol 25:1539–1544PubMedCrossRefGoogle Scholar
- 9.Grothey A, Hart LL, Rowland KM, et al. (2008) Intermittent oxaliplatin (oxali) administration and time-to-treatment-failure (TTF) in metastatic colorectal cancer (mCRC): Final results of the phase III CONcePT trial. J Clin Oncol 26S: Abstr 4010.Google Scholar
- 12.National Cancer Institute-Common Toxicity Criteria. (NCI-CTC Version 3.0, March 31, 2003).Google Scholar
- 14.Yasui H, Hamaguchi T, Shimada Y, et al. (2008) A multicenter phase-II study of 5-FU, leucovorin and oxaliplatin (FOLFOX6) in patients with previously untreated metastatic colorectal cancer. The 4th Annual Meeting of Japanese Society of Clinical Oncology P-183Google Scholar
- 19.Hochster HS, Grothey A, Shpilsky A, Childs BH (2008) Effect of intravenous calcium and magnesium versus placebo on response to FOLFOX + bevacizumab in the CONcePT trial. J Clin Oncol (ASCO-GI 2008 Abstract No.280)Google Scholar