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

Abstract

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 À2 ) and oral S-1 at a fixed dose of 40 mg m À2 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 À2 , 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 À2 in combination with S-1 40 mg m À2 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.

Phase I/II study of S-1 combined with paclitaxel in patients with unresectable and/or recurrent advanced gastric cancer

“…Ajani et al (2005) reported that a combination of docetaxel, cisplatin, and fluorouracil is highly active against advanced untreated gastric or gastroesophageal adenocarcinoma. Docetaxel has also been combined with TS-1, and available evidence indicates that this combination is effective and well tolerated in patients with advanced gastric cancer (Yamaguchi et al, 2006).…”

Phase I study of S-1, docetaxel and cisplatin combination chemotherapy in patients with unresectable metastatic gastric cancer

“…The recent introduction of a new oral drug, S-1 (Shirasaka et al, 1996), which was developed on the basis of biochemical modulation to inhibit dihydropyrimidine dehydrogenase and orotate phosphoribosyltransferase to therapeutic modality for gastric cancer, has enabled us to increase ORR to 46 -74% and MST to 10.9 -14.8 months by its combination with cisplatin (CDDP), docetaxel or CTP-11, with less toxicity than 5-FU (Koizumi et al, 2003;Ajani et al, 2006;Inokuchi et al, 2006;Yamaguchi et al, 2006).…”

“…In combination with CDDP, 5-FU or CDDP plus 5-FU or S-1, docetaxel has shown a higher ORR of 37 to 56% and MST of 9.0 to 14.3 months (Roth et al, 2000;Thuss-Patience et al, 2005;Van Cutsem et al, 2006;Yamaguchi et al, 2006).…”

A randomized phase 2 study of docetaxel and S‐1 versus docetaxel and cisplatin in advanced gastric cancer with an evaluation of SPARC expression for personalized therapy

“…[5][6][7] Docetaxel showed synergism with S-1 in vitro, and the response rate was 46%-67% in several phase 2 trials. [9][10][11] Based on these findings, we designed a randomized phase 2 study to determine whether S-1 or cisplatin shows greater promise as a combination partner of docetaxel for a subsequent phase 3 study. We adopted a weekly docetaxel regimen to assess whether split administration improves drug tolerability and tested the predictive values of biomarkers for treatment-related outcomes.…”