Phase I study of biweekly intravenous paclitaxel plus intraperitoneal cisplatin and paclitaxel for gastric cancer with peritoneal metastasis.

Objectives: A phase I study of biweekly intravenous (IV) paclitaxel (PTX) plus intraperitoneal (IP) cisplatin (CDDP) and PTX was performed to determine the maximum tolerated dose (MTD) and recommended dose (RD) in gastric cancer patients.

Methods: Nine gastric cancer patients with peritoneal metastasis were enrolled. PTX was administered intravenously at a dose of 100 mg/m(2) and intraperitoneally with an initial dose of 20 mg/m(2) (level 1), stepped up to 30 or 40 mg/m(2) depending on observed toxicity. CDDP was administered intraperitoneally at a dose of 30 mg/m(2) over 24 h. PTX and CDDP were administered on days 1 and 15 in 4-week cycles.

Results: The MTD was determined to be dose level 1, as 2 of 3 patients experienced dose-limiting toxicities (DLTs), grade 4 leukopenia and grade 3 vomiting. Therefore, the doses of IV PTX, IP CDDP and IP PTX were reduced to 80, 25 and 20 mg/m(2), respectively (level 0). Consequently, the RD was determined to be dose level 0, as only 1 of 6 patients experienced DLT, grade 3 nausea.

Conclusions: Combination chemotherapy of IV PTX plus IP CDDP and PTX was shown to be a safe regimen that should be further explored in clinical trials.