A randomized phase II study of neoadjuvant chemoradiotherapy with 5-fluorouracil/leucovorin or irinotecan/S-1 in patients with locally advanced rectal cancer
Mené en Corée du Sud sur 142 patients atteints d'un cancer rectal de stade localement avancé (durée médiane de suivi : 43,8 mois), cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse pathologique complète, et la toxicité d'une radiothérapie néoadjuvante en combinaison avec une chimiothérapie concomitante par 5-fluorouracile/leucovorine ou irinotécan/S-1
Purpose : The purpose of this study was to evaluate the rate of pathologic complete response (pCR) in patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (CRT) with 5-fluorouracil /leucovorin(FL) versus irinotecan/S-1 (IS) Methods and Materials : Patients with resectable LARC (clinical stage T3/4 and/or lymph node positive) were randomly assigned to receive preoperative radiation (45-50.4 Gray in 25–28 daily fractions) and concomitant chemotherapy with either a bolus injection of FL (400 mg/m2/day 5-fluorouracil and 20 mg/m2/day leucovorin) for 3 consecutive days every 4 weeks for 2 cycles (FL group), or with 40 mg/m2 irinotecan on days 1, 8, 15, 22, and 29, and 35 mg/m2 S-1 twice on the day of irradiation (IS group). Curative surgery was performed approximately 4–8 weeks after the completion of CRT. The postoperative chemotherapy regimen was FL with a primary endpoint of a pCR rate evaluation. Results : One hundred forty-two eligible patients were randomly assigned, and the median follow-up duration was 43.8 months (95% CI, 40.8–46.8 months). One hundred thirty-three patients (93.7%) out of 142 underwent total mesorectal excision. pCR was achieved in 11 (16.7%) of 66 patients in the FL group and 17 (25.8%) out of 67patients in the IS group (p=0.246). When good responders were defined as patients with Mandard Grade 1 and 2, the rate of good responders was significantly higher in the IS group compared to the FL group (54.6% vs. 36.4%, respectively, p=0.036). The preoperative rates of grade 3-4 toxicities were higher in the IS group (7.0%) compared to the FL group (1.4%, p=0.095). The 3-year disease-free survival was not significantly different between the two groups (79.7% vs. 76.6%, respectively, p=0.896). Conclusions : IS-based preoperative CRT did not increase pCR rate, but increased acute toxicities compared with standard 5-FU treatment, and therefore,further investigation is needed.
http://www.redjournal.org/article/S0360-3016%2815%2903194-6/abstract