Phase I/II study of a combination of capecitabine, cisplatin, and intraperitoneal docetaxel (XP ID) in advanced gastric cancer patients with peritoneal metastasis
- 376 Downloads
This study was conducted to determine the recommended dose (RD) of intraperitoneal docetaxel (ID) in combination with systemic capecitabine and cisplatin (XP) and to evaluate its efficacy and safety at the RD in advanced gastric cancer (AGC) patients with peritoneal metastasis.
AGC patients with peritoneal metastasis received XP ID, which consists of 937.5 mg/m2 of capecitabine twice daily on days 1–14, 60 mg/m2 of intravenous cisplatin on day 1, and intraperitoneal docetaxel at 3 different dose levels (60, 80, or 100 mg/m2) on day 1, every 3 weeks. In the phase I study, the standard 3 + 3 method was used to determine the RD of XP ID. In the phase II study, patients received RD of XP ID.
In the phase I study, ID 100 mg/m2 was chosen as the RD, with one dose-limiting toxicity (ileus) out of six patients. The 39 AGC patients enrolled in the phase II study received the RD of XP ID. The median progression-free survival was 11.0 months (95% CI 6.9–15.1), and median overall survival was 15.1 months (95% CI 9.1–21.1). The most frequent grade 3/4 adverse events were neutropenia (38.6%) and abdominal pain (30.8%). The incidence of abdominal pain cumulatively increased in the later treatment cycles.
Our study indicated that XP ID was effective, with manageable toxicities, in AGC patients with peritoneal metastasis. As the cumulative incidence of abdominal pain was probably related to bowel irritation by ID, it might be necessary to modify the dose.
KeywordsGastric cancer Chemotherapy Peritoneal metastasis
A part of the study medication (Docetaxel) was provided by Sanofi-Aventis Korea Ltd.
Compliance with ethical standards
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions. Informed consent was obtained from all patients for being included in the study.
Conflict of interest
Yoon-Koo Kang is a consultant for Roche, Novartis, Sanofi, Ono, Daehwa, Bristol-Myers Squibb, AstraZeneca, and Blueprint. Sook Ryun Park has received a speaker honorarium from Roche. The authors have no other conflicts of interest to declare.
- 5.Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, et al. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol. 2006;24:4991–7.CrossRefPubMedGoogle Scholar
- 9.Rober J, Morgan J, Doroshow JH, Synold T, et al. Phase I trial of intraperitoneal docetaxel in the treatment of advanced malignancies primarily confined to the peritoneal cavity: dose-limiting toxicity and pharmacokinetics. Clin Cancer Res. 2003;9(16):5896–901.Google Scholar
- 17.Fushida S, Kinoshita J, Yagi Y, Funaki H, Kinami S, Ninomiya I, et al. Dual anti-cancer effects of weekly intraperitoneal docetaxel in treatment of advanced gastric cancer patients with peritoneal carcinomatosis: a feasibility and pharmacokinetic study. Oncol Rep. 2008;19:1305–10.PubMedGoogle Scholar
- 21.Rosen HR, Jatzko G, Repse S, Potrc S, Neudorfer H, Sandbichler P, et al. Adjuvant intraperitoneal chemotherapy with carbon-adsorbed mitomycin in patients with gastric cancer: results of a randomized multicenter trial of the Austrian Working Group for Surgical Oncology. J Clin Oncol. 1998;16:2733–8.CrossRefPubMedGoogle Scholar
- 25.Ishigami H, Fujiwara Y, Fukushima R, et al. Phase III study of intraperitoneal paclitaxel plus s-1/paclitaxel compared with s-1/cisplatin in gastric cancer patients with peritoneal metastasis: PHOENIX-GC trial [abstract]. ASCO Meet Abstr. 2016;34:4014.Google Scholar