Phase II study of S-1, docetaxel and cisplatin combination chemotherapy in patients with unresectable metastatic gastric cancer
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We evaluated the activity and toxicity of docetaxel, cisplatin, and S-1 (DCS) combination chemotherapy in patients with unresectable metastatic gastric cancer.
Patients with histologically proven, unresectable metastatic gastric adenocarcinoma, performance status (PS) 0–2, and no prior chemotherapy were eligible. Patients received oral S-1 (40 mg/m2 b.i.d.) on days 1–14 and intravenous cisplatin (60 mg/m2) and docetaxel (60 mg/m2) on day 8 every 3 weeks.
Thirty-four patients were enrolled between March 2005 and April 2007. Three patients were considered ineligible and did not receive the DSC therapy. Clinical characteristics were as follows: median age, 63 years (range, 44–77); PS, 0/1/2: 23/8/0; women/men, 8/23; and well-differentiated/undifferentiated adenocarcinoma, 10/21. The objective response rate was 87.1% with 1 complete response (3.2%) and 26 partial responses (83.9%) in 31 assessable patients. Four had stable disease (12.9%) but none had progressive disease. Of these 27 responders, 8 (25.8%) achieved downstaging and 7 (22.6%) underwent curative surgery. The median survival time and progression-free survival were 687 days [confidence interval (95% CI), 600.0–1,138.1] and 226 days (95% CI, 182.5–379.3), respectively. Most common grade 3/4 hematologic toxicity was neutropenia (77.4%). Most common grade 3 nonhematologic toxicities included anorexia (35.5%) and nausea (32.3%). All treatment-related toxicities resolved, and no toxic deaths were observed.
DCS combination chemotherapy is highly active against unresectable metastatic gastric cancer and can be given safely with proper management of adverse events. Further studies of this combination are warranted.
KeywordsGastric cancer Docetaxel Cisplatin S-1 Chemotherapy
We thank the following doctors for their assistance in this study. Hiroyuki Nagashima, M.D., Gangi Kuroiwa, M.D., Michiaki Hirayama, M.D., Shinichi Katsuki, M.D., Hiroshi Muramatsu, M.D., Hiroyuki Kuroda, M.D., Fourth Department of Internal Medicine, Sapporo Medical University, School of Medicine, Sapporo, Japan and Tomoko Sonoda, M.D., Department of Public Health, Sapporo Medical University, School of Medicine, Sapporo, Japan.
- 7.Ohtsu A, Shimada Y, Shirao K et al (2003) Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: the Japan clinical oncology group study (JCOG9205). J Clin Oncol 21:54–59CrossRefPubMedGoogle Scholar
- 12.Ajani JA, Rodriquez W, Bodoky G et al (2009) Multicenter phase III comparison of cisplatin/S-1 (CS) with cisplatin/5-FU (CF) as first-line therapy in patients with advanced gastric cancer (FLAGS): secondary and subset analyses. ASCO Annual Meeting Proceedings. J Clin Oncol 27:15s (abstr 4511)CrossRefGoogle Scholar
- 13.Einzig AI, Neuberg D, Remick SC et al (1996) Phase II trial of docetaxel (taxotere) in patients with adenocarcinoma of the upper gastrointestinal tract previously untreated with cytotoxic chemotherapy: the eastern cooperative oncology group (ECOG) results of protocol E1293. Med Oncol 13:87–93CrossRefPubMedGoogle Scholar
- 19.Nishi M, Omori Y, Miwa Y (1999) Response assessment of chemotherapy and radiotherapy for gastric carcinoma part IV. Kanehara Shuppan, TokyoGoogle Scholar
- 20.Therasse P, Arbuck SG, Eisenhauer EA et al (2000) New guidelines to evaluate the response to treatment in solid tumors. European organization for research and treatment of cancer, national cancer institute of the united states, national cancer institute of canada. J Natl Cancer Inst 92:205–216CrossRefPubMedGoogle Scholar
- 22.Vanhoefer U, Rougier P, Wilke H et al (2000) Final results of a randomized phase III trial of sequential high-dose methotrexate, fluorouracil, and doxorubicin versus etoposide, leucovorin, and fluorouracil versus infusional fluorouracil and cisplatin in advanced gastric cancer: a trial of the european organization for research and treatment of cancer gastrointestinal tract cancer cooperative group. J Clin Oncol 18:2648–2657PubMedGoogle Scholar
- 27.Dank M, Zaluski J, Barone C et al (2008) Randomized phase III study comparing irinotecan combined with 5-fluorouracil and folinic acid to cisplatin combined with 5-fluorouracil in chemotherapy naive patients with advanced adenocarcinoma of the stomach or esophagogastric junction. Ann Oncol 19:1450–1457CrossRefPubMedGoogle Scholar
- 34.Chau I, Norman AR, Cunningham D, Waters JS, Oates J, Ross PJ (2004) Multivariate prognostic factor analysis in locally advanced and metastatic esophago-gastric cancer—pooled analysis from three multicenter, randomized, controlled trials using individual patient data. J Clin Oncol 22:2395–2403CrossRefPubMedGoogle Scholar
- 39.Gallardo-Rincon D, Onate-Ocana LF, Calderillo-Ruiz G (2000) Neoadjuvant chemotherapy with P-ELF (cisplatin, etoposide, leucovorin, 5-fluorouracil) followed by radical resection in patients with initially unresectable gastric adenocarcinoma: a phase II study. Ann Surg Oncol 7:45–50CrossRefPubMedGoogle Scholar
- 44.Sym SJ, Chang HM, Ryu MH et al. (2009) Neoadjuvant docetaxel, capecitabine and cisplatin (DXP) in patients with unresectable locally advanced or metastatic gastric cancer. Ann Surg Oncol 26 (Epub ahead of print)Google Scholar