S-1 plus oxaliplatin combined with radiation (SOX/RT) for preoperative locally advanced rectal carcinoma: final results of a phase II study (JACCRO CC-04: SHOGUN trial)

Abstract

Background: The study was designed to evaluate the safety and efficacy of adding oxaliplatin to preoperative chemoradiotherpy (CRT) with S-1, an oral fluoropyrimidine in patients with locally advanced rectal carcinoma (LARC). We report here final results of the study. Methods: Patients with histopathologically confirmed LARC (cT3-T4, any N) were eligible. They received oral S-1 (80 mg/m2/day on days 1-5, 8-12, 22-26, and 29-33) and infusional oxaliplatin (60 mg/m2/day on 1, 8, 22, 29) plus radiotherapy (1.8Gy/ day, a total dose of 50.4 Gy in 28 fractions), with a chemotherapy gap in the third week of radiotherapy. Primary endpoint of the study was pCR rate. Secondary endpoints were R0 resection rate, down-staging rate, cumulative 3-year local recurrence rate, 3-year disease free survival (DFS) and toxicity. Results: Forty five patients were enrolled at six centers in Japan. All the patients received CRT, and 44 underwent operation. The pCR rate was 27.3 % (12/44). The R0 resection rate was 95.5 % (42/44). T- down-staging rate was 59.1% (26/44), and Ndown- staging rate was 65.9 % (29/44): the combined pathological down-staging rate was 79.5 % (35/44). There were no grade 4 adverse events, and 11.1% of the patients had grade 3 adverse events. No patients suffered from local recurrence. Therefore, cumulative 3-year local recurrence rate was 0%. However, 13 (29.5%) patients suffered from distant metastasis and one patient suffered from a secondary cancer (esophageal cancer). Eight patients had lung metastasis, and 4 had liver metastasis. Three patients died of the metastatic disease. The 3-year DFS of the 44 patients was 67.5% (median follow up 36.3 month), and the 3-year overall survival (OS) was 93.0%. Then the patients were divided into two groups: pCR (12) and non pCR (32) groups. The 3-year DFS of each group was 91.7% and 58.1%, respectively. The 3-year OS was 100% and 90.3%, respectively. Conclusions: The study showed a high pCR rate with no severe acute toxicity with good follow up results. Therefore, addition of oxaliplatin to preoperative CRT with S-1 in patients with LARC might be feasible and lead to a better local control than standard treatment.