High dose cisplatin and high dose carboplatin in refractory ovarian cancer

High dose cisplatin (40 mg/m2 qd x 5) and high dose carboplatin (400 mg/m2 qd x 2) were administered to advanced ovarian cancer patients who were refractory to standard therapy which included standard dose cisplatin regimens. Cisplatin was administered in 250 ml of 3% saline with 61 per day of saline hydration while carboplatin was administered in 500 ml D5W by continuous infusion for 48 hours. Objective responses were observed in 6/19 (32%) patients treated with high dose cisplatin and an additional 8 patients (42%) had minor responses or stable disease. The preliminary response rate in an ongoing phase II trial of high dose CBDCA is 33% (4/12 patients). There have been no responses to high dose CBDCA in patients who were resistant to high dose cisplatin. The dose limiting toxicity of high dose cisplatin is a peripheral neuropathy while high dose carboplatin results in severe, but reversible, myelosuppression. High dose carboplatin was less emetogenic than cisplatin and did not produce renal toxicity or peripheral neuropathy. In addition, in vitro cytotoxicity studies in cisplatin sensitive and resistant human ovarian cancer cell lines demonstrated a steep dose response relationship with both cisplatin and carboplatin and extensive cross resistance between these two platinum analogs. Studies are currently in progress to determine the efficacy and toxicity of high dose cisplatin or high dose carboplatin combined with alkylating agents in previously untreated advanced ovarian cancer patients.