Postoperative irinotecan in resected stage II-III rectal cancer. Final analysis of the French R98 intergroup trial
Mené en France sur 357 patients atteints d'un cancer du rectum de stade II-III (durée de suivi : 156 mois), cet essai randomisé évalue l'efficacité, du point de vue de la survie sans maladie, de l'ajout d'irinotecan à un traitement adjuvant combinant fluorouracile et leucovorine
Résumé en anglais
Backgroud : The R98 trial explores the addition of irinotecan to a 5FU plus leucovorin (5FU/LV) adjuvant regimen in optimally resected stages II-III rectal cancers. We report the updated long-term results. Disease free survival (DFS) was the primary end-point.
Patients and Methods : Between March 1999 and December 2005, 357 patients were randomized: 178 in 5FU/LV and 179 in LV5FU2+irinotecan arm. The trial was stratified by control arm: Mayo-Clinic regimen or LV5FU2 regimen.
Results Three hundred and fifty seven randomized patients were evaluable for efficacy. With a follow-up of 156 months, the DFS was in favour of experimental arm but did not reach statistical significance (HR=0.80, p=0.154). The same was observed for OS (HR=0.87, p=0.433). The 5-year DFS was 58 % in the control arm and 63 % in the experimental arm. The 5-year OS was 74 % in the control arm and 75 % in the experimental arm.Patients allocated to the experimental arm had more grade 3-4 neutropenia when compared with the LV5FU2 arm (33 % vs 6 %, p=0.03), but not when compared with the Mayo Clinic arm (33% vs 36%, p=0.84). Grade 3-4 diarrhea tended to be higher in the experimental arm, but analyses stratified by control arm or by radiotherapy failed to show significant differences across strata (test for interaction p=0.44).
Conclusion : Even though a benefit of irinotecan in subgroups of patients cannot be excluded, due to early termination and lack of power, the study does not support the addition of irinotecan to 5FU/LV in routine in patients with resected stage II-III rectal cancer.
