683P - Phase I study of weekly intraperitoneal docetaxel combined with capecitabine and cisplatin for gastric cancer with peritoneal metastasis

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Gastric Cancer
Presenter Hironori Ishigami
Citation Annals of Oncology (2014) 25 (suppl_4): iv210-iv253. 10.1093/annonc/mdu334
Authors H. Ishigami1, J. Kitayama2, H. Yamaguchi2, T. Watanabe2
  • 1Department Of Chemotherapy, The University of Tokyo, 113-8655 - Tokyo/JP
  • 2Department Of Surgical Oncology, The University of Tokyo, 113-8655 - Tokyo/JP

Abstract

Aim

Intraperitoneal (IP) chemotherapy is a promising treatment option for gastric cancer with peritoneal metastasis. The safety and efficacy of IP docetaxel (DOC) combined with systemic chemotherapy have been reported recently. Capecitabine and cisplatin (XP) demonstrated efficacy in a phase III study, and is regarded as the standard regimen for unresectable and metastatic gastric cancer worldwide. We designed a new regimen combining weekly IP DOC and XP, and carried out a dose-escalation study in order to determine the maximum-tolerated dose (MTD) and recommended dose (RD).

Methods

Gastric cancer patients with peritoneal metastasis were enrolled. DOC was administered intraperitoneally at a dose of 10 mg/m2 on days 1 and 8. Capecitabine was administered orally at a dose of 1000 mg/m2 bid for 14 days followed by a 7-day rest. Cisplatin was administered intravenously with an initial dose of 60 mg/m2 (level 1), stepped up to 80 mg/m2 (level 2) depending on observed toxicity. This combination chemotherapy was repeated every 3 weeks. Toxicity was graded according to CTCAE v4.0. Dose-limiting toxicities (DLTs) were defined as grade 4 leukopenia, grade 3 febrile neutropenia, grade 3 thrombocytopenia, and grade 3 non-hematological toxicity. The MTD was defined as the dose level at which 2 or more of 3 or 6 patients developed DLTs. The RD was defined as one dose level under the MTD.

Results

A total of 12 patients were enrolled, and were fully evaluated for toxicity. At dose level 1, 6 patients developed no DLTs. At dose level 2, one of the 3 initial patients experienced grade 3 anorexia, and an additional 3 patients developed no DLTs. Consequently, the MTD was not reached, and the RD of CDDP was determined to be 80 mg/m2 (level 2). As for adverse events probably related to IP DOC, 7 patients experienced grade 1 abdominal pain, and 6 patients experienced grade 1 edema.

Conclusions

Combination chemotherapy with IP DOC and XP was shown to be a safe regimen that should be further explored in clinical trials.

Disclosure

All authors have declared no conflicts of interest.