Phase III noninferiority trial comparing irinotecan with oxaliplatin, fluorouracil, and leucovorin in patients with advanced colorectal carcinoma previously treated with fluorouracil: N9841
Kim GP et al. - In a trial to determine whether overall survival (OS) of fluorouracil (FU)-refractory pts was noninferior when treated with second-line infusional FU, leucovorin, and oxaliplatin (FOLFOX4; arm B) vs irinotecan (arm A), it was confirmed that in pts who experienced treatment failure with front-line FU therapy, OS does not significantly differ whether second-line therapy begins with irinotecan or FOLFOX4. FOLFOX4 produces higher response rates (RR) and longer time to progression (TTP). Both arms had notable OS in pts who experienced treatment failure with first-line FU therapy. Methods- Pts who experienced treatment failure with 1 prior FU-based therapy and had not received prior irinotecan or oxaliplatin, either for metastatic disease or within 6 mos of adjuvant FU therapy, were randomly assigned to arm A (irinotecan 350 or 300 mg/m2 every 3 wks) or arm B (FOLFOX4).
Results- 491 pts were randomly assigned (arm A, n=245; arm B, n=246); 288 (59%) had experienced treatment failure with FU for metastatic colorectal cancer.
- 227 pts (46%) received protocol-mandated third-line therapy (arm A, 43%; arm B, 57%).
- Median survival was 13.8 mos for initial treatment with FOLFOX4 and 14.3 mos for irinotecan.
- RR (28% vs 15.5%) and TTP (6.2 vs 4.4 mos) were significantly superior with FOLFOX4.
- In the nonrandom subset of pts who crossed over, RR and TTP improvements with FOLFOX4 continued into third-line treatment.
- Irinotecan therapy was associated with more grade 3 nausea, vomiting, diarrhea, and febrile neutropenia; FOLFOX4 was associated with more neutropenia and paresthesias.
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