The oral fluoropyrimidine S-1 is effective as adjuvant chemotherapy for stage III colon cancer, according to findings from the randomized, open-label, phase III noninferiority trial in Japan.
Disease-free survival was 75.5% at 3 years in 758 patients with curatively resected stage III colon cancer who were randomized to receive S-1, compared with 72.5% in 760 such patients who received tegafur-uracil plus leucovorin (stratified hazard ratio for disease-free survival, 0.85), Dr. M. Yoshida of Osaka Medical College Hospital, Osaka, Japan, and colleagues, reported online Aug. 14 in Annals of Oncology. The findings were reported on behalf of the Adjuvant Chemotherapy Trial of TS-1 for Colon Cancer (ACTS-CC) study group.
The stratified hazard ratio for disease-free survival was similar even after excluding 14 patients who did not receive the allocated treatment, and after adjusting for key baseline factors (Ann. Oncol. 2014 Aug. 14 [doi:10.1003/annonc/mdu232]).
The findings demonstrate the efficacy of S-1 by confirming its noninferiority to tegafur-uracil plus leucovorin (UFT/LV), the investigators said.
Postoperative adjuvant chemotherapy for patients with stage III colon cancer is the standard of care internationally, and Western guidelines call for first-line treatment with intravenous 5-fluorouracil (5-FU) and leucovorin (LV) or capecitabine combined with oxaliplatin (the FOLFOX or CapeOX regimens). Fluoropyrimidine monotherapy is also a treatment option.
"In Japan, oral fluoropyrimidine derivatives have been preferred because of their convenience, leading to the development of several oral fluoropyrimidine derivatives with different properties," the investigators explained, noting that UFT/LV (uracil and tegafur/leucovorin) has been shown in two trials to be noninferior to intravenous 5-FU/LV, and is commonly used for adjuvant chemotherapy for stage III colon cancer patients in Japan.
"S-1 is another oral fluoropyrimidine approved in Japan for various cancers, including colorectal cancer, and for gastric cancers in a total of 38 countries," they said.
S-1, which combines tegafur, gimeracil, and oteracil, has been shown in phase III studies to be noninferior to conventional 5-FU–based regimens when used in combination with other cytotoxic agents for the treatment of advanced gastric cancer and advanced colorectal cancer.
As adjuvant chemotherapy, postoperative S-1 treatment significantly improved survival in patients with gastric cancer and pancreatic cancer, but its efficacy for colon cancer had not been established, they noted.
Patients included in the current study were aged 20-80 years (median, 66 years), and 35.3% were aged 70 years or older. Those assigned to the S-1 group received 80-120 mg daily (depending on body surface area) on days 1-28, every 42 days for four courses; those assigned to the UFT/LV group received 300-600 mg of UFT daily (depending on body surface area) and 75 mg of LV daily on days 1-28, every 35 days for five courses.
No significant differences were noted between the S-1 and UFT/LV groups with respect to safety and feasibility.
The findings suggest that S-1 could be a new treatment option – with multiple potential advantages over UFT/LV – for adjuvant chemotherapy in patients with colon cancer, the investigators said.
Among the advantages are lower cost (in Japan, the cost is half that of UFT/LV), dosing convenience (twice daily after meals vs. every 8 hours but not within 1 hour of meals for UFT/LV), and dramatically reduced risk of hand-foot syndrome, compared with capecitabine (1.3% vs. 60%), they said, noting that studies are ongoing to assess the cost-effectiveness of S-1 and to compare S-1 and capecitabine as adjuvant chemotherapy for stage III colon cancer. An age subgroup analysis is also underway to assess the potential role of oral fluoropyrimidines in adjuvant chemotherapy for elderly patients.
This study was supported by the Foundation for Biomedical Research and Innovation, Translational Research Informatics Center, under a funding contract with Taiho Pharmaceutical, Japan. Dr. Yoshida reported receiving honoraria and/or research funding from Taiho Pharmaceutical, Takeda Pharmaceutical, Chugai Pharmaceutical, Bristol-Myers Squibb, Merck Serono, Bayer Yakuhin, Daiichi Sankyo, Sanofi, Kyowa Hakko Kirin, Nippon Kayaku, Ono Pharmaceutical, and Jansen Pharmaceutical.