Cyclosporin A Reverses Chemoresistance in Patients With Gynecologic Malignancies1

Multidrug resistance is a major obstacle in successful systemic therapy of gynecologic malignancies. The objectives of this study are to evaluate the activity of cyclosporin A used to overcome drug resistance in a variety of gynecologic malignancies. Forty women (29 with ovarian cancer, 7 with uterine cancer, 3 with cervical cancer, and 1 with choriocarcinoma) were treated with cyclosporin A, 4 mg/kg intravenously, 6 hours before and 18 hours after the specific chemotherapeutic agent, to which the tumor had developed drug resistance. All patients had shown resistance to the chemotherapy agent used in combination with cyclosporin A. All patients had been heavily pretreated (mean, 2.8 previous chemotherapy regimens). Overall, among 38 available patients with gynecologic malignancies, a 29% objective response rate was observed. Twenty-six (65%) of all patients received three or more cycles of cyclosporin A. There was a 25% response rate for patients with ovarian cancer patients and 50% for those with uterine cancer. There were no responses among the three patients with cervical cancer, and the patient with choriocarcinoma had a complete response. All patients were evaluable for toxicity. Leukopenia and nausea were the most common toxic reactions, but in most cases they were transient, and only three patients required a treatment delay. The most common grade 3 or 4 toxicity was thrombocytopenia, which was observed in 22% of the patients. Cyclosporin A is well tolerated and has significant potential for reversal of chemoresistance in heavily pretreated patients with ovarian and uterine malignancies.