A dose-escalation study of docetaxel, oxaliplatin, and S-1 (DOS) as a first-line therapy for patients with unresectable metastatic gastric cancer
The aim of this study was to determine the recommended dose (RD) for a docetaxel/oxaliplatin/S-1 (DOS) regimen in patients with unresectable gastric cancer and to preliminarily evaluate its efficacy.
Previously untreated patients with histologically proven unresectable metastatic gastric cancer were enrolled (n = 16). Docetaxel and oxaliplatin were administered intravenously on day 8 and S-1 was administered orally twice a day on days 1–14. Each cycle was repeated every 3 weeks. Dose-limiting toxicities (DLTs) were evaluated during the first treatment cycle. Three dose escalations of DOS were employed in this study: level 1 (50/100/80 mg/m2), level 2 (50/130/80 mg/m2), and level 3 (60/130/80 mg/m2).
According to the 3 + 3 dose-escalating schedule, we determined that the RD and maximum tolerated dose for this regimen were level 1 and level 2, respectively. The DLTs were grade 3 diarrhea and febrile neutropenia. The overall response rate was 78% (7/9) for patients with measurable lesions and consisted of two complete responses and five partial responses. Five patients underwent conversion surgery. The median follow-up time was 19 months with median survival time and progression-free survival being 19.6 months and 7.6 months, respectively.
The results from this study demonstrated the safety and tolerability of DOS in unresectable metastatic gastric cancer patients and revealed promising preliminary efficacy with a high conversion rate. A phase II trial of DOS regimen using the identified RD is ongoing.
KeywordsGastric cancer S-1 Docetaxel Oxaliplatin Phase I Conversion therapy
Compliance with ethical standards
Conflict of interest
The authors have no conflicts of interest to declare.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Human and animal rights
This article does not contain any studies with animals performed by any of the authors.
Informed consent was obtained from all individual participants included in the study.
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