A PHASE-I TRIAL OF INTRAPERITONEAL CARBOPLATIN AND ETOPOSIDE WITH GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR SUPPORT IN PATIENTS WITHINTRAABDOMINAL MALIGNANCIES

Background. Although somewhat controversial, there are data to suggest that patients with ovarian cancer may experience a survival advantage if the dose intensity of platinum-containing regimens can be maximize d. Administration of chemotherapeutic agents via the intraperitoneal r oute offers the opportunity to increase dose intensity of several chem otherapeutic agents. Methods. The authors conducted a Phase I trial of intraperitoneal carboplatin and etoposide in combination with granulo cyte macrophage colony stimulating factor (GM-CSF) in an attempt to de termine the maximum tolerated dose of carboplatin. The starting dose f or carboplatin was 300 mg/m(2) and for etoposide 400 mg/m(2). The dose of carboplatin was escalated while the etoposide was maintained at th e initial dose. The total dose of each agent was calculated and given daily over 3 days in amounts equal to one-third of the total dose. On day 1 of therapy, one-third of the dose was mixed in 2 liters of dextr ose (D5W) and administered intraperitoneally (IP) as rapidly as possib le. On Days 2 and 3, one-third of the dose was mixed in 1 liter of D5W and administered similarly. GM-CSF was begun on Day 4 as a subcutaneo us injection at a dose of 500 mu g/m(2)/d. Results. Unacceptable hemat ologic toxicity was encountered at a carboplatin dose of 800 mg/m(2); therefore, a carboplatin dose of 600 mg/m(2) is recommended for Phase II studies. An overall response rate of 54% with a complete response r ate of 17% was observed in patients with ovarian cancer. The overall r esponse rate for all patients was 45%. Conclusion, Because of the sign ificant toxicity encountered in this study, it is recommended that thi s regimen be used only in the context of a clinical study. The recomme nded Phase II study dose for this combination is carboplatin 600 mg/M( 2) and a total dose of etoposide 400 mg/M(2) total dose given as three equal parts IP over 3 days. GM-CSF should begin on Day 4 at a dose of 500 mu g/m(2)/day subcutaneously and should continue until the absolu te neutrophil count is greater than 1000 granulocytes on 3 successive days.