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 ovarian epithelial tumors, squamous carcinomas of the cervix, trophoblastic disease, and untreated uterine sarcomas in Gynecologic Oncology Group (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 undertaken.
METHODS: Fifty-two patients with advanced adenocarcinoma of the endometrium recurrent after surgery and/or radiation therapy and refractory to first-line chemotherapeutic agents were treated with ifosfamide, 1.2 g/m2 intravenous daily for 5 days every 4 weeks, and mesna, 300 mg/m2 intravenous every 4 hours for 3 doses daily for 5 days. Two patients were ineligible--one due to prior therapy and one due to a second malignancy. Three patients had an inadequate trial, and 7 were inevaluable for response, leaving 47 patients evaluable for toxicity and 40 patients evaluable for response. Thirty-seven patients had undergone hysterectomy, 30 had received radiation therapy, and 32 had received prior cisplatin-based chemotherapy. All patients were GOG performance status 0, 1, or 2.
RESULTS: Complete responses were observed in three (7.5%) and partial responses in three patients (7.5%), for a response 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.
CONCLUSIONS: This dose and schedule of ifosfamide and mesna is active in patients with adenocarcinoma of the endometrium failing platinum-based therapy. Phase II testing in untreated patients is under way.