Safety of cisplatin combined with continuous 5-FU versus bolus 5-FU and leucovorin, in metastatic gastrointestinal cancer (FFCD 9404 randomised trial)

Jacqueline Duffour, Olivier Bouché, Philippe Rougier, Chantal Milan, Laurent Bedenne, Jean François Seitz, Bruno Buecher, Jean Louis Legoux, Michel Ducreux, Denis Vetter, Jean Luc Raoul, Eric François, Marc Ychou

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    Résumé

    Background: The objective of this phase III study was to compare the safety and efficacy of FLP (modulation of 5-FU (Fluorouracil) by folinic acid or leucovorin (LV) and cisplatin vs. FP (5-FU combined with Cisplatin) as a first line chemotherapy in advanced oesophageal, gastric and pancreatic cancer. Patients and Methods: 232 patients with measurable lesions were randomised to receive at the first cycle either FP (arm A: 5-FU 800 mg/m2/d in continuous infusion 5 days and cisplatin 100 mg/m2 on day 1 or 2), or FLP (arm B: LV, 100 mg/m2/d in bolus 5 days, followed by 5-FU 350 mg/m2/d in 1 h infusion 5 days and cisplatin 100 mg/m2 on day 1 or 2). In case of no grade 3-4 haematological and diarrhoea toxicity, the dose of 5-FU was increased to 1,000 mg/m2/d and 400 mg/m 2/d in the two arms respectively, for the subsequent cycles until disease progression. Results: The distribution of primary tumours was: 19 squamous cell carcinoma of the oesophagus, 19 oesophageal adenocarcinoma, 91 gastric and 97 pancreatic adenocarcinoma. Safety remained acceptable and comparable in the two arms except for the severe grade 3-4 mucositis, which was lower in arm B (4.5 vs. 16.4%, p<0.009). Efficacy in terms of tumour response and survival was similar in the two arms, showing an objective response rate (after external review) of 18.6% (95% confidence interval (CI) 11.4-25.8%) in arm A vs. 15% (95% CI 8.5-21.6%) in arm B, an overall median survival of 24 weeks in arm A vs. 24.7 in arm B (p=0.83) and a progression-free median survival of 12.4 weeks vs. 12.1 in arms A and B, respectively (p=0.91). Conclusion: The FLP regimen is substantially equivalent to FP in terms of safety and quality of life, as well as for antitumour efficacy in these carcinomas; the only slight advantage of FLP in this study concerns mucositis. Based on these results, FLP could be used as an alternative to FP when appropriate.

    langue originaleAnglais
    Pages (de - à)3877-3883
    Nombre de pages7
    journalAnticancer Research
    Volume26
    Numéro de publication5 B
    étatPublié - 1 sept. 2006

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