NO BENEFIT OF OXALIPLATIN WITH CHEMORADIATION FOR RECTAL CANCER

J Clin Oncol. 2010 Mar 1. [Epub ahead of print]

Comparison of Two Neoadjuvant Chemoradiotherapy Regimens for Locally Advanced Rectal Cancer: Results of the Phase III Trial ACCORD 12/0405-Prodige 2.

Gérard JP, Azria D, Gourgou-Bourgade S, Martel-Laffay I,0Hennequin C, Etienne PL, Vendrely V, François E, de La Roche G, Bouché O, Mirabel X, Denis B, Mineur L, Berdah JF, Mahé MA, Bécouarn Y, Dupuis O, Lledo G, Montoto-Grillot C, Conroy T.

Centre Antoine-Lacassagne; Université Nice Sofia Antipolis, Nice; Centre Val d'Aurelle, Montpellier; Centre Léon Bérard; Hôpital privé Jean Mermoz, Lyon; Hôpital St Louis; Fédération Nationale des Centres de Lutte Contre le Cancer, Paris; Clinique Armoricaine de Radiologie, St Brieuc; Hôpital Saint André, Bordeaux; Institut de Cancérologie de La Loire, St Priest en Jarez; Centre Hospitalier Universitaire Robert Debré, Reims; Centre Oscar Lambret, Lille; Hôpital Pasteur, Colmar; Institut Ste Catherine, Avignon; Clinique Ste Marguerite, Hyères; Centre René Gauducheau, Nantes St Herblain; Institut Bergonié, Bordeaux; Clinique Victor Hugo, Le Mans; and Centre Alexis Vautrin, Vandoeuvre-Les-Nancy, France.

PURPOSE: Neoadjuvant chemoradiotherapy is considered a standard approach for T3-4 M0 rectal cancer. In this situation, we compared neoadjuvant radiotherapy plus capecitabine with dose-intensified radiotherapy plus capecitabine and oxaliplatin. PATIENTS AND METHODS: We randomly assigned patients to receive 5 weeks of treatment with radiotherapy 45 Gy/25 fractions with concurrent capecitabine 800 mg/m(2) twice daily 5 days per week (Cap 45) or radiotherapy 50 Gy/25 fractions with capecitabine 800 mg/m(2) twice daily 5 days per week and oxaliplatin 50 mg/m(2) once weekly (Capox 50). The primary end point was complete sterilization of the operative specimen (ypCR). RESULTS: Five hundred ninety-eight patients were randomly assigned to receive Cap 45 (n = 299) or Capox 50 (n = 299). More preoperative grade 3 to 4 toxicity occurred in the Capox 50 group (25 v 11%; P < .001). Surgery was performed in 98% of patients in both groups. There were no differences between groups in the rate of conservative surgery (75%) or postoperative deaths at 60 days (0.3%). The ypCR rate was 13.9% with Cap 45 and 19.2% with Capox 50 (P = .09). When ypCR was combined with yp few residual cells, the rate was respectively 28.9% with Cap 45 and 39.4% with Capox 50 (P = .008). The rate of positive circumferential rectal margins (between 0 and 2 mm) was 19.3% with Cap 45 and 9.9% with Capox 50 (P = .02). CONCLUSION: The benefit of oxaliplatin was not demonstrated and this drug should not be used with concurrent irradiation. Cap 50 merits investigation for T3-4 rectal cancers.