Phase II study of neoadjuvant treatment of sequential S-1-based concurrent chemoradiotherapy followed by systemic chemotherapy with gemcitabine for borderline resectable pancreatic adenocarcinoma (HOPS-BR 01)
Mené au Japon sur 45 patients atteints d'un adénocarcinome canalaire du pancréas à la limite de la résécabilité, cet essai de phase II évalue l'efficacité, du point de vue du taux de résection R0, d'un traitement néo-adjuvant comportant une chimiothérapie à base de S-1, une radiothérapie concomitante puis une chimiothérapie systémique par gemcitabine
Background : Preoperative treatment is recommended for borderline resectable pancreatic ductal adenocarcinoma (BR-PC). However, the standard treatment has not yet been determined. We conducted a multicenter phase II study to investigate the efficacy of neoadjuvant treatment of sequential chemoradiation followed by chemotherapy. Methods : All enrolled patients were treated by preoperative chemoradiation (a total dose of 50.4 Gy/28 fractions and orally administered S-1 at 80 mg/m2 on the day of irradiation) followed by chemotherapy [administration of gemcitabine at 1000 mg/m2/dose on days 1, 8, and 15 in 3 cycles of 4 weeks], and attempted curative resection. The primary outcome was R0 resection rate among patients who completed preoperative treatment and pancreatectomy. The threshold of the R0 resection rate was defined as 74% based on a previous study of upfront surgery. Results : Forty-five patients were included. Twenty-one patients could not undergo pancreatectomy because of progressive diseases (n = 14), adverse events (n = 5), and consent withdrawal (n = 2), and 4 patients underwent additional resection after dropping out. The resection rates were 53.3% and 62.2% in the per protocol set (PPS) and full analysis set (FAS) populations, respectively. The R0 resection rates were 95.8% (95%CI: 78.9%-99.9%) and 96.4% (81.7%-99.9%) in the PPS and FAS populations, respectively. The median overall survival and progression-free survival of all the included patients were 17.3 and 10.5 months, respectively. The median survival time of the patients with pancreatectomy was significantly longer than that of the patients without pancreatectomy in the PPS (27.9 vs. 12.3 months; P = 0.001) and FAS populations (32.2 vs. 11.8 months; P < 0.001). Conclusion : This study revealed that a long duration of preoperative treatment of sequential chemoradiation followed by systemic chemotherapy provides a high rate of R0 resection and sufficient survival time in patients undergoing pancreatectomy.
International Journal of Radiation Oncology, Biology, Physics