N9741: FOLFOX (oxaliplatin(Oxal)/ 5-fluorouracil (5-FU)/ leucovorin (LV) or reduced dose R-IFL (CPT-11 + 5-FU/LV) in advanced colorectal cancer (CRC): Final efficacy data from an intergroup study

Abstract

3621 Background: After reducing doses of CPT-11 from 125 to 100 (doses in mg/m2) and 5FU from 500 to 400 (LV unchanged, 20 ) due to increased toxicity & early mortality (Rothenberg, JCO 2001), Intergroup N9741 concurrently randomized 355 of a planned 600 patients (pts) with CRC to FOLFOX-4 or R-IFL. Randomization was terminated early due to superior results on FOLFOX. Methods: The regimens were: FOLFOX 4 (Oxal 85 d 1 + LV 200/5-FU 400 bolus + 600 as a 22 hour infusion d 1,2 q 2 week); R-IFL (CPT-11 100 + LV 20/5FU bolus 400 weekly x 4, q 6 week. Results: Pts/arm were: FOLFOX-154, R-IFL-151. 60 day all-cause mortality was FOLFOX 2.0%, R-IFL 2.7%. Common grade ≥3 toxicities are below. With median follow-up of 18.0 months, median time to progression (TTP) (primary endpoint) for FOLFOX is significantly better than for R-IFL: 10.1 vs 6.5 months (mo) respectively (Logrank p<0.0001). The median survival (OS) is significantly greater for FOLFOX than R-IFL: 20.5 vs 16.3 mo (p = 0.026). Confirmed response rates (RR) were improved for FOLFOX vs. R-IFL (47% vs 32%, p=0.007). Sixty-five percent of pts received second line Rx with 75% in each arm receiving the agent not used in their first line treatment (in contrast to earlier phases of the study when access to Oxal was limited by availability). Conclusions: R-IFL lessens the toxicity burden of IFL, and results in efficacy similar to full dose IFL (median TTP 6.9 mo, RR 32%, median OS 15 months (Goldberg, JCO 2004)). FOLFOX improves RR, TTP, and OS compared to R-IFL. These results suggest that R-IFL, while not the best primary treatment option, retains activity with less toxicity than IFL, and may have utility as a platform for adding targeted therapies to IFL. Supported by NIH Grant CA25224, Pharmacia and Sanofi-Synthelabo. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pharmacia/Pfizer; Sanofi-Synthelabo Sanofi-Synthelabo Pharmacia/Pfizer; Sanofi-Synthelabo; NCI Sanofi-Synthelabo