A Phase II Study of Docetaxel, Oxaliplatin and S-1 (DOS) in Patients With Advanced Gastric Cancer
Docetaxel is an anti-microtubule agent. Docetaxel is an active agent for gastric cancer,
with response rate (RR) of 20-24% as a single agent and RR of 37-40% as a combination
therapy with 5-FU and/or cisplatin.
S-1 is a new oral dihydropyrimidine dehydrogenase (DPD) inhibitory fluoropyrimidine (DIF).
In two late phase II studies of S-1 for advanced gastric cancer, RR was 45%, with very low
(2%) incidence of grade 3 toxicity.
Recent phase I/II trial of the combination of docetaxel and S-1 in patients with advanced
gastric cancer suggests that repeated 3-4 week cycles of S-1 60-80mg/m2 /day for 14 days
combined with docetaxel 40-75mg/m2 is feasible.
Oxaliplatin, diaminocyclohexane-platinum, is an alkylating agent inhibiting DNA replication.
Comparing to cisplatin or carboplatin, oxaliplatin appear to be more effective and has a
more favorable toxicity profile. Phase II studies of the combination of docetaxel and
oxaliplatin in patients with advanced gastric cancer suggests that docetaxel 60 or 75mg/m2
combined with oxaliplatin 130 or 80mg/m2 every 3 weeks is feasible.
Recent dose finding study of the combination of docetaxel, oxaliplatin and S-1 (DOS) in
patients with advanced gastric cancer suggests that docetaxel 52.5mg/m2 on day 1 and
oxaliplatin 105mg/m2 on day 1 combined with S-1 80mg/m2 on day1 to day 14 every 3 weeks is
Docetaxel, S-1 and oxaliplatin have distinct mechanisms of action and no overlapped key
toxicities. Furthermore, fluoropyrimidine and docetaxel or oxaliplatin have shown synergism
in vivo studies and in clinical trials. Based on these results, the combination of DOS is a
reasonable candidate of new chemotherapeutic regimen for the advanced gastric cancer.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
overall response rate
Dae Young Zang, MD, PhD
Hallym University Medical Center
Korea: Food and Drug Administration