Phase I II study of docetaxel and S-1 in patients with advanced gastric cancer

• Published in: British journal of cancer Vol. 94; no. 12; pp. 1803 - 1808
• Main Authors: Yamaguchi, K, Shimamura, T, Hyodo, I, Koizumi, W, Doi, T, Narahara, H, Komatsu, Y, Kato, T, Saitoh, S, Akiya, T, Munakata, M, Miyata, Y, Maeda, Y, Takiuchi, H, Nakano, S, Esaki, T, Kinjo, F, Sakata, Y
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 19.06.2006
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - mortality; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Clinical Study; Docetaxel; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Male; Maximum Tolerated Dose; Oxonic Acid - adverse effects; Stomach Neoplasms - drug therapy; Stomach Neoplasms - mortality; Survival Analysis; Survival Rate; Taxoids - adverse effects; Tegafur - adverse effects; Treatment Outcome
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6603196

The aims of this phase I/II study of docetaxel and S-1 were to determine the dose-limiting toxicity (DLT), maximum-tolerated dose (MTD), and recommended dose (RD) in the phase I part and to explore the tumour response, survival and safety in the phase II part. Patients with histologically- or cytologically confirmed unresectable or recurrent gastric cancer were eligible. Treatment consisted of intravenous docetaxel on day 1 (starting dose 50 mg m(-2)) and oral S-1 at a fixed dose of 40 mg m(-2) twice daily on days 1-14, every 4 weeks up to six cycles. Nine patients took part in the phase I portion of the study. The MTD of docetaxel was determined to be 50 mg m(-2), with the DLTs of grade 3 infection associated with grade 3 neutropenia and grade 4 neutropenia during S-1 administration. The RD of docetaxel was 40 mg m(-2) in combination with S-1 40 mg m(-2) b.i.d. The efficacy and safety of this regimen was therefore assessed in 46 patients with at least one measurable lesion. The overall response rate and estimated median overall survival were 46% (95% CI, 31-61%) and 14.0 months (8.3-17.3 months), respectively. The most common grade 3/4 toxicity was neutropenia (67% of patients), which was predictable and manageable. This regimen showed promising activity with moderate toxicities in advanced gastric cancer.