Intraperitoneal infusion of paclitaxel with S-1 for peritoneal metastasis of advanced gastric cancer: phase I study.

BACKGROUND

Intraperitoneal administration of taxanes revealed excellent anti-tumor effect for peritoneal metastasis of gastric cancer in some experimental models. The aim of this study is to determine maximum tolerated dose (MTD), dose limiting toxicity (DLT) and recommended dose (RD) of intraperitoneally infused paclitaxel (PTX) with S-1 as a phase I study.

PATIENTS AND METHODS

Eighteen patients with advanced gastric cancer in addition to confirmed peritoneal metastasis using laparoscopy were enrolled in this study. The regimen consists of oral administration of S-1 (Dose 80 mg: BSA<1.25 m(2), 100 mg: 1.25<BSA<1.5 m(2), 120 mg: BSA>1.5 m(2)) for 14 days and intraperitoneal infusion of PTX (Dose escalation: level I: 40, II: 60, III: 80, level IV: 90, V: 100 mg/m(2)) at day 1 and 14. PTX concentrations in serum and ascites were determined at 4, 8, 12, 24, 48 hours after the infusion, which was repeated twice every 4 weeks.

RESULTS

The number of patients were as follows: Level I: 3, Level II: 6, Level III: 3, Level IV: 3, Level V: 3. Grade 3 leukocytopenia was confirmed in 1 (Level II) and 2 (Level V). MTD is 90 mg/m(2), RD is 80 mg/m(2) and DLT is Grade 3 leukocytopenia. The average serum PTX concentrations remained in optimal range except for all 3 of level V patients. In all cohorts, the PTX concentrations in the ascites were approximately 1000 folds higher than those in serum for 48 hours after the infusion.

CONCLUSIONS

MTD and RD were PTX 90 mg/m(2), 80 mg/m(2), respectively. These findings were supported by pharmocokinetics of PTX.