[Preoperative intraperitoneal versus intravenous carboplatin chemotherapy for advanced gastric cancer, pharmacokinetics and drug accumulation study].

OBJECTIVE

To examine the accumulation of anticancer drugs in tumor tissues by different routes of administration.

METHODS

Pharmacokinetic comparison of preoperative intraperitoneal (i.p.) and intravenous (i.v.) carboplatin chemotherapy was done in 10 patients each with advanced, resectable gastric cancer. Preoperatively, 300 mg/m2 carboplatin in 750 ml 0.9% sodium chloride was administered by i.p. or i.v. At 160-180 minutes after drug administration, peritoneal fluid, portal vein blood and peripheral blood were taken. At 240-270 minutes later, cancer tissues, peritumor normal tissues, omentum majus, peritoneum and cancer-free lymph nodes were collected during operation. Total carboplatin concentrations were measured by high performance liquid chromatography (HPLC).

RESULTS

High concentrations of carboplatin were found in all tissues by i.p. administration. Drug concentration was highest in the peritonaeum, being 4 times as high as that after i.v. administration. Cancer tissue had higher drug concentration than did peritumor normal tissues. Compared to those after i.v. administration, concentrations in the peritoneal fluid, portal vein blood and peripheral blood were 13, 3 and 1.5 times as high, respectively. No significant differences were observed in drug concentrations in the peritoneum, omentum majus and lymph nodes after i.v. administration.

CONCLUSION

For gastric cancer, carboplatin chemotherapy by i.p. administration is a better route for clinical practice.