Adjuvant S-1 Supported For Japanese Stage II/III Rectal Cancer Patients

S-1 may be a standard regimen for Japanese patients after stage II or III rectal cancer surgery with curative intent

medwireNews: Phase III study findings indicate that adjuvant S-1 – a combination of tegafur, gimeracil and oteracil potassium – may be superior to tegafur–uracil (UFT) for Japanese patients with curatively resected stage II or III rectal cancer.

Five-year relapse-free survival was achieved by 66.4% of 479 patients randomly assigned to receive open-label S-1 for 1 year compared with 61.7% for 480 patients given UFT, a significant difference with a hazard ratio of 0.77.

A year of S-1 treatment has become “a standard adjuvant chemotherapy regimen” for this population, the authors write in the Annals of Oncology, adding that it can be “considered an important option, especially for patients who have not received preoperative [chemoradiation therapy]”.

However, 5-year rates of overall survival were a comparable 82.0% and 80.2% for the S-1 and UFT treatment groups. And 5-year cumulative rates of local recurrence (9.8 vs 13.0%) and distant recurrence (24.7 vs 26.9%) were also similar.

“The reason that no difference in overall survival of both arms was found is probably that the unexpectedly favorable survival rate achieved through post-trial treatment of patients after recurrence in both arms caused the follow-up period of 5.5 years to be too short and the study to be underpowered”, suggest Eiji Oki, from Kyushu University in Fukuoka, Japan, and co-workers.

The S-1 group received a dose of 80–120 mg/day in 4-week cycles, with a 2-week break, while UFT was given at a dose of 500–600 mg/day on days 1–5 followed by a 2-day rest period.

Safety analysis reported adverse events in 82.3% of patients given S-1 versus 73.9% of UFT-treated patients. Grade 3 or more severe effects occurred in a comparable 13.4% and 11.7% of patients, respectively, with both groups experiencing diarrhoea and reduced haemoglobin.

One year of treatment was completed by 61.3% of the S-1 group and 61.8% of the UFT group, indicating that “compliance was favorable”, the researchers say.

In all, 93.9% and 98.3% of the S-1 and UFT patients who experienced recurrent disease went onto receive further treatment after the trial ended.

Eiji Oki and team note that the cumulative local recurrence rate for S-1 is “not inferior” to that reported in Western studies of preoperative treatment and the cumulative distant recurrence rate “seems to be superior” to such reports.

“Rectal cancer patients will greatly benefit from being able to undergo surgery without preoperative therapy and taking only oral drugs for adjuvant chemotherapy”, they observe.

However, the authors question whether differences in pharmacokinetics and pharmacodynamics of S-1 allow their results to be directly extrapolated to patients of a different ethnic origin.

“For instance, S-1 could potentially cause a high incidence of gastrointestinal toxicities in Caucasian patients if administered at the dose used in this study”, they suggest.


Oki E, Murata A, Yoshida K, et al. A randomized phase III trial comparing S-1 versus UFT as adjuvant chemotherapy for stage II/III rectal cancer (JFMC35-C1: ACTS-RC). Ann Oncol 2016; Advance online publication 7 April. doi: 10.1093/annonc/mdw162

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