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)

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 N- down-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.

Clinical trial identification

NCT01227239, Oct 18 2010

Legal entity responsible for the study

Toshiaki Watanabe

Funding

Taiho Pharmaceutical Co Ltd., Japan

Disclosure

T. Watanabe: Membership on an advisory board: Taiho Pharmaceutical honoraria: Yakult Honsha, Taiho Pharmaceutical All other authors have declared no conflicts of interest.