Objective: Because of preliminary observations favoring the use of mitomycin, doxorubicin, and cisplatin (MAP) chemotherapy in leiomyosarcomas, the Gynecologic Oncology Group (GOG) decided to conduct a phase II clinical trial of this combination regimen in patients with advanced disease.
Methods: Patients with histologically confirmed uterine leiomyosarcoma who had not previously received cytotoxic drugs were considered for participation in this clinical trial. Eligible patients had measurable disease, GOG performance status 0-2, and adequate bone marrow, renal, and hepatic function according to standard criteria. Mitomycin 8 mg/m(2) and doxorubicin 40 mg/m(2) were each given by iv injection followed immediately by cisplatin 60 mg/m(2) in 1 liter of 0.45% saline plus mannitol 25 g. Patients who remained free from tumor progression or intolerable toxicity received at least three, to a maximum of six, cycles of MAP.
Results: Forty-one patients were registered, of whom 4 were determined ineligible (wrong cell type, 2; wrong site of origin, 1; inadequate pathology material, 1). Thirty-five of the 37 were evaluable for response after receiving from one to six (median three) cycles of MAP. Three patients (9%) achieved a complete response and 5 (14%) exhibited a partial response. The most common adverse effects were leukopenia (33 patients) and thrombocytopenia (30 patients). Pulmonary toxicity was seen in 10 patients and was a factor in the clinical deterioration and death of 2.
Conclusion: MAP is active against advanced uterine leiomyosarcomas, but not remarkably so. Despite its low therapeutic index, this novel, possibly interactive, combination may serve as a forerunner to regimens that more efficiently exploit the enhancement of sarcoma cell kill under hypoxic conditions.