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
2004; Lippincott Williams & Wilkins; Volume: 22; Issue: 14_suppl Linguagem: Inglês
10.1200/jco.2004.22.14_suppl.3621
ISSN1527-7755
AutoresRichard M. Goldberg, Daniel J. Sargent, Roscoe F. Morton, Charles S. Fuchs, R. K. Ramanathan, Stephen K. Williamson, B. Findlay, H. Pitot, Steven R. Alberts,
Tópico(s)Genetic factors in colorectal cancer
Resumo3621 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
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