Definitive chemoradiotherapy with FOLFOX versus fluorouracil and cisplatin in patients with oesophageal cancer (PRODIGE5/ACCORD17): final results of a randomised, phase 2/3 trial.
Abstract | BACKGROUND: METHODS: We did a multicentre, randomised, open-label, parallel-group, phase 2/3 trial of patients aged 18 years or older enrolled from 24 centres in France between Oct 15, 2004, and Aug 25, 2011. Eligible participants had confirmed stage I-IVA oesophageal carcinoma ( adenocarcinoma, squamous-cell, or adenosquamous), Eastern Cooperative Oncology Group (ECOG) status 0-2, sufficient caloric intake, adequate haematological, renal, and hepatic function, and had been selected to receive definitive chemoradiotherapy. Patients were randomly assigned (1:1) to receive either six cycles (three concomitant to radiotherapy) of oxaliplatin 85 mg/m(2), leucovorin 200 mg/m(2), bolus fluorouracil 400 mg/m(2), and infusional fluorouracil 1600 mg/m(2) (FOLFOX) over 46 h, or four cycles (two concomitant to radiotherapy) of fluorouracil 1000 mg/m(2) per day for 4 days and cisplatin 75 mg/m(2) on day 1. Both groups also received 50 Gy radiotherapy in 25 fractions (five fractions per week). Random allocation to treatment groups was done by a central computerised randomisation procedure by minimisation, stratified by centre, histology, weight loss, and ECOG status, and was achieved independently from the study investigators. The primary endpoint was progression-free survival. Data analysis was primarily done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00861094. FINDINGS: 134 participants were randomly allocated to the FOLFOX group and 133 to the fluorouracil and cisplatin group (intention-to-treat population), and 131 patients in the FOLFOX group and 128 in the fluorouracil and cisplatin group actually received the study drugs (safety population). Median follow-up was 25·3 months (IQR 15·9-36·4). Median progression-free survival was 9·7 months (95% CI 8·1-14·5) in the FOLFOX group and 9·4 months (8·1-10·6) in the fluorouracil and cisplatin group (HR 0·93, 95% CI 0·70-1·24; p=0·64). One toxic death occurred in the FOLFOX group and six in the fluorouracil- cisplatin group (p=0·066). No significant differences were recorded in the rates of most frequent grade 3 or 4 adverse events between the treatment groups. Of all-grade adverse events that occurred in 5% or more of patients, paraesthesia (61 [47%] events in 131 patients in the FOLFOX group vs three [2%] in 128 patients in the cisplatin- fluorouracil group, p<0·0001), sensory neuropathy (24 [18%] vs one [1%], p<0·0001), increases in aspartate aminotransferase concentrations (14 [11%] vs two [2%], p=0·002), and increases in alanine aminotransferase concentrations (11 [8%] vs two [2%], p=0·012) were more common in the FOLFOX group, whereas serum creatinine increases (four [3%] vs 15 [12%], p=0·007), mucositis (35 [27%] vs 41 [32%], p=0·011), and alopecia (two [2%] vs 12 [9%], p=0·005) were more common in the fluorouracil and cisplatin group. INTERPRETATION: FUNDING: UNICANCER, French Health Ministry, Sanofi-Aventis, and National League Against Cancer.
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Authors | Thierry Conroy, Marie-Pierre Galais, Jean-Luc Raoul, Olivier Bouché, Sophie Gourgou-Bourgade, Jean-Yves Douillard, Pierre-Luc Etienne, Valérie Boige, Isabelle Martel-Lafay, Pierre Michel, Carmen Llacer-Moscardo, Eric François, Gilles Créhange, Meher Ben Abdelghani, Beata Juzyna, Laurent Bedenne, Antoine Adenis, Fédération Francophone de Cancérologie Digestive and UNICANCER-GI Group |
Journal | The Lancet. Oncology
(Lancet Oncol)
Vol. 15
Issue 3
Pg. 305-14
(Mar 2014)
ISSN: 1474-5488 [Electronic] England |
PMID | 24556041
(Publication Type: Clinical Trial, Phase II, Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2014 Elsevier Ltd. All rights reserved. |
Chemical References |
- Organoplatinum Compounds
- Cisplatin
- Leucovorin
- Fluorouracil
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Topics |
- Adult
- Aged
- Aged, 80 and over
- Antineoplastic Combined Chemotherapy Protocols
(therapeutic use)
- Chemoradiotherapy
- Cisplatin
(administration & dosage)
- Disease-Free Survival
- Esophageal Neoplasms
(mortality, therapy)
- Female
- Fluorouracil
(administration & dosage, therapeutic use)
- Humans
- Leucovorin
(therapeutic use)
- Male
- Middle Aged
- Organoplatinum Compounds
(therapeutic use)
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