PHASE-II STUDY OF IFOSFAMIDE AND MESNA IN REFRACTORY ADENOCARCINOMA OF THE ENDOMETRIUM - A GYNECOLOGIC-ONCOLOGY-GROUP STUDY

Background. Ifosfamide has antitumor activity in previously treated ov arian epithelial tumors, squamous carcinomas of the cervix, trophoblas tic disease, and untreated uterine sarcomas in Gynecologic Oncology Gr oup (GOG) trials. Because cyclophosphamide and other alkylating agents are known to produce responses in adenocarcinoma of the endometrium, a Phase II trial of ifosfamide and the uroprotector, mesna, was undert aken. Methods. Fifty-two patients with advanced adenocarcinoma of the endometrium recurrent after surgery and/or radiation therapy and refra ctory to first-line chemotherapeutic agents were treated with ifosfami de, 1.2 g/m(2) intravenous daily for 5 days every 4 weeks, and mesna, 300 mg/m(2) intravenous every 4 hours for 3 doses daily for 5 days. Tw o patients were ineligible-one due to prior therapy and one due to a s econd malignancy. Three patients had an inadequate trial, and 7 were i nevaluable for response, leaving 47 patients evaluable for toxicity an d 40 patients evaluable for response. Thirty-seven patients had underg one hysterectomy, 30 had received radiation therapy, and 32 had receiv ed prior cisplatin-based chemotherapy. All patients were GOG performan ce status 0, 1, or 2. Results. Complete responses were observed in thr ee (7.5%) and partial responses in three patients (7.5%), for a respon se rate of 15% (95% confidence interval for the true response rate was 5.5%-29.8%). Severe (Grade 3 or 4) leukopenia and anemia were seen in 25 and 4 patients, respectively. Severe thrombocytopenia was observed in 7 patients. Five patients had Grade 3 or 4 neurotoxicity, and one had Grade 3 renal impairment. Reversible alopecia was universal. Concl usions. This dose and schedule of ifosfamide and mesna is active in pa tients with adenocarcinoma of the endometrium failing platinum-based t herapy. Phase II testing in untreated patients is under way.