HIGH-VOLUME INTRAPERITONEAL CHEMOTHERAPY WITH METHOTREXATE IN PATIENTS WITH CANCER

Abstract

The use of high-volume i.p. chemotherapy with methotrexate (7.5-50 .mu.M methotrexate administered via peritoneal dialysis technique) was studied in 4 patients with ovarian cancer and 1 patient with malignant melanoma. All had tumor localized to the peritoneal cavity or liver. Methotrexate concentration in the peritoneum could be maintained 18- to 36-fold higher than corresponding plasma concentrations using this method, plasma levels remaining in the range of 0.2 to 3 .mu.M. While local toxicity was generally limited and manageable, mild aseptic peritoneal irritation was commonly seen; 1 episode of bacterial peritonitis did occur. Because of the concentration difference between peritoneum and the systemic circulation, systemic toxicity was moderate with only 6 of 29 treatment cycles resulting in myelosuppression. No definite therapeutic benefit was seen, but the tumors of 4 of 5 patients had demonstrated resistance to a methotrexate-containing chemotherapeutic regimen prior to this study. Further investigation of this novel treatment modality is warranted. This study provides the 1st measurement of peritoneal methotrexate clearance and the ratio of peritoneal to total body clearance.