Phase II trial comparing folinic acid, fluorouracil, and gemcitabine (FFG) and FOLFOX4 regimens with added bevacizumab (B) in metastatic colorectal cancer (mCRC)

Abstract

e15098 Background: FOLFOX4 is a standard chemotherapy for mCRC. FFG has shown substantial activity in mCRC. This trial compared the safety and efficacy of FFG and FOLFOX4 regimens in patients (pts) with mCRC. B was added to each arm after FDA approval in 2004 as first-line treatment of mCRC. Methods: Pts with mCRC, chemonaïve except for adjuvant treatment, were randomized to two treatment arms: FFG given weekly for 6 weeks of an 8-week cycle; FOLFOX4 had a 2-week cycle. Pts in both groups received B at 5 mg/kg every 2 weeks. Treatment continued until disease progression. Planned enrollment was 150 pts. Primary endpoint was overall response rate (ORR); secondary endpoints included toxicity, overall survival (OS), and time to progression (TTP). Response was assessed by RECIST. Post-hoc analysis of disease control rate (DCR) was added. Results: Forty-two pts (18 pts given B) were randomized to each arm. Thirty-one cycles of FFG and 248 cycles of FOLFOX4 were delivered. FFG produced greater myelosuppression than FOLFOX4. Two cases each of MI and DVT were observed in the FOLFOX4(B) subgroup; one pt had DVT with FFG alone. The incidence of gastrointestinal hemorrhage was low and similar for FFG and FOLFOX4. Peripheral neuropathy was highest in the FOLFOX4(B) subgroup. ORR and DCR were significantly greater for FOLFOX4(B) than for FFG(B). Median TTP and OS were not statistically different for FFG and FOLFOX4 groups. The trial was stopped due to low enrollment; planned statistical power was not achieved. Conclusions: FFG and FOLFOX4 regimens were generally well tolerated, with greater neuropathy in FOLFOX4 and greater myelosuppression in FFG. ORR was greatest in the FOLFOX4(B) subgroup. TTP and OS results comparing FFG and FOLFOX4 groups were inconclusive due to low enrollment. Rapid changes in mCRC “standard of care” during this trial may have constrained pt accrual. [Table: see text] [Table: see text]