mesna and Endometrial-Neoplasms

To determine the effectiveness and toxicity of ifosfamide chemotherapy in women with metastatic or recurrent endometrial stromal sarcomas unexposed to other chemotherapy.. In a prospective, multi-institutional phase II study conducted by the Gynecology Oncology Group, the starting dose of ifosfamide was 1.5 g/m2 given daily intravenously (i.v.) for 5 days (reduced to 1.2 g/m2 daily in patients who had previously received radiotherapy). Mesna (2 mercaptoethane sodium sulfonate) was given i.v. immediately and at 4 and 8 hours after the administration of ifosfamide. Each dose of mesna was 20% of the total daily dose of ifosfamide. Patients were treated every 3 weeks if blood counts permitted. Therapy was discontinued if there was progression of the cancer or unacceptable toxicity.. Twenty-two patients were entered into this study. One was excluded from analysis because of the wrong histologic type, leaving 21 evaluable for response and toxicity. Gynecologic Oncology Group grade 3 or 4 granulocytopenia occurred in four patients (19%), and one patient each experienced Gynecologic Oncology Group grade 4 anemia and genitourinary toxicity. Three patients experienced complete tumor responses and four had partial responses, for an overall response rate of 33.3%.. Ifosfamide is active in the therapy of women with chemotherapy-naive metastatic or recurrent endometrial stromal sarcomas.

Topics: Antineoplastic Agents, Alkylating; Drug Administration Schedule; Endometrial Neoplasms; Female; Humans; Ifosfamide; Mesna; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Sarcoma, Endometrial Stromal

In other Gynecologic Oncology Group (GOG) studies, ifosfamide demonstrated antineoplastic activity against ovarian epithelial tumors, squamous carcinomas of the cervix, uterine sarcomas, and trophoblastic disease. Responses were also observed in 15% of patients with endometrial adenocarcinoma previously exposed to chemotherapy. This is a phase II trial of ifosfamide in patients with chemotherapy-naive advanced or recurrent endometrial adenocarcinoma. Thirty-seven patients with advanced adenocarcinoma of the endometrium recurrent after surgery and/or radiotherapy were treated with ifosfamide 1.2 g/m2 intravenously daily for 5 days every 4 weeks and mesna 300 mg/m2 intravenously every 4 hr for 3 doses daily for 5 days with each course. Three patients were ineligible--one due to a second primary, one did not have an endometrial primary, and the other because of wrong cell type. One patient was inevaluable for response; thus, 33 were evaluable for response. All patients had undergone hysterectomy and 24 had received radiotherapy before entering the trial. Eleven had GOG performance status of 0, 18 had a status of 1, and 4 had performance status of 2. Median age was 68 years (range, 41-86 years). Grade 3 or 4 neutropenia occurred in eight patients each and grade 3 thrombocytopenia was observed in one patient. One patient had a grade 4 neurotoxicity. Complete responses were observed in two patients (6.1%) and partial responses in six (18.2%) for an overall response rate of 24.3%. Ifosfamide in this dose and schedule is an active drug in the treatment of patients with advanced or recurrent adenocarcinoma of the endometrium.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Drug Therapy, Combination; Endometrial Neoplasms; Female; Humans; Ifosfamide; Mesna; Middle Aged; Neoplasm Recurrence, Local; Treatment Outcome

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.. 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.. 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.. 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.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Combined Modality Therapy; Endometrial Neoplasms; Female; Humans; Ifosfamide; Mesna; Middle Aged; Neoplasm Recurrence, Local