(CHICAGO, IL)—Chemoradiotherapy with FOLFOX does not improve progression-free survival (PFS) compared with cisplatin and 5-FU in patients with esophageal cancer and has similar toxicities, according to the final results of the phase 3 PRODIGE 5/ACCORD 17 trial presented at the 2012 American Society of Clinical Oncology Annual Meeting.
Chemoradiotherapy “is one of the best treatment options for localized esophageal cancer,” but new combinations are required to improve safety and survival, said Thierry Conroy, MD, of Nancy University and Centre Alexis Vautrin in Nancy, France, on behalf of the UNICANCER-GI/FFCD PRODIGE Intergroup, in explaining the study’s rationale.
The phase 3, randomized study enrolled 267 patients between October 2004 and August 2011. Eligibility criteria included previously untreated adenocarcinoma or squamous cell esophageal cancer (any T, N0 or N1, M0 or M1a) that was technically unresectable. Patients who had surgical contraindications or refused to undergo surgery were also included. The primary endpoint was PFS; main secondary endpoints were OS, grade 3-4 toxicities, and quality of life.
In both study arms, the radiation dose was 50 Gy (2Gy/fr) 5 days per week for 5 weeks. In Arm A, patients received 6 bimonthly cycles of oxaliplatin 85mg/m2 on Day 1 and leucovorin 200mg/m2 followed by 5-FU 400mg/m2 bolus Day 1, then 1,600mg/m2 46h continuous infusion. The first 3 cycles were delivered during radiotherapy; the other 3, after radiotherapy. In Arm B, patients received 4 cycles of cisplatin 75mg/m2 day 1 followed by 5FU 1,000mg/m2/day continuous infusion days 1-4; the first 2 cycles were administered during radiotherapy and the other 2, following radiotherapy.
The majority of the patients in both arms were male (81%); median age was 61 years and 53% had a performance status of 0. Squamous cell esophageal cancer was diagnosed in 85.8%; 52% of patients had stage III disease, 6.0% stage IV A, and 3.0%, stage IV B.
Full treatment was delivered to 67.9% of patients in Arm A and 72.2% in Arm B. A total of 7 toxic deaths occurred in each arm. Grade 3/4 toxicities in both arms were neutropenia, febrile neutropenia, anemia, and asthenia.
At a median follow-up of 25.3 months, 3-year PFS was 18.2% in Arm A and 17.4% in Arm B (HR 1.07). Median overall survival was 20.2 months in Arm A and 17.5 months in Arm B (HR 1.06). Complete response rates were comparable in both arms.
The investigator concluded that definitive chemo with Folfox does not improve PFS in unresectable localized esophageal cancer.