mesna and Genital-Neoplasms--Female

In July 1985, the Gynecologic Oncology Group initiated a series of phase II trials with ifosfamide/mesna in advanced or recurrent gynecologic malignancies. Previously untreated patients received ifosfamide 1.5 g/m2/d intravenously (IV) for 5 days. Mesna was given IV every 4 hours for three doses after ifosfamide administration at a dose of 20% of the daily ifosfamide dose. All patients with ovarian cancer and 87% of those with cervical cancer had had prior platinum-based therapy. Because of the toxicity encountered in previously treated patients with ovarian carcinoma, the dose of ifosfamide was reduced to 1.2 g/m2/d in those who had had prior chemotherapy or radiotherapy. In epithelial ovarian carcinoma, responses were observed in eight (20%) of 41 evaluable patients, with three (7%) complete responses (CRs). Response duration was 2.1 to 20.3+ months (median, 6.9+ months). In squamous carcinoma of the cervix, 3 (11.1%) of 27 evaluable patients had partial responses (PRs) of 1.8-, 2.2-, and 3.1-month duration. Of 26 untreated patients with mixed mesodermal tumors of the uterus, 5 (19.2%) had CRs and 3 (11.5%) had PRs, for an overall response rate of 30.7%. Response duration was 1.4+ to 8.6 months, with a median of 3.8 months. Toxicity included two deaths from renal insufficiency and a third related to neurologic impairment. Hematologic toxicity was manageable. Ifosfamide/mesna has activity in a wide range of gynecologic malignancies.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Combined Modality Therapy; Drug Administration Schedule; Drug Evaluation; Female; Genital Neoplasms, Female; Hematologic Diseases; Humans; Ifosfamide; Leiomyosarcoma; Mesna; Middle Aged; Multicenter Studies as Topic; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Remission Induction; Uterine Cervical Neoplasms; Uterine Neoplasms

Fourteen evaluable patients with gynecologic adenocarcinoma (7 ovarian, 4 endometrial, 2 peritoneal and one breast cancer) were treated with ifosfamide (1 g/m2 X 5 days), adriamycin (50 mg/m2) and cisplatin (50 mg/m2) combined chemotherapy (IAP). All the patients had measurable disease, and three were refractory cases who had received prior chemotherapy including two CAP (cyclophosphamide, adriamycin and cisplatin). To avoid hemorrhagic cystitis induced by ifosfamide, uroprotective mesna (400 mg/body X 3) was used following ifosfamide infusion. The 5-day schedule of IAP treatment brought a 100% response rate in these patients. Complete responses were observed in 3 patients and lasted 6, 10 and 12 months. Partial responses were achieved in 11 patients including two with CAP refractory ovarian cancer, although the remission in previously treated patients was of short duration. Hematologic side effects of the IAP regimen were severe, showing grade 4 leucopenia in 85.7% of the patients, and it required maximal anti-infection treatments. Mesna resulted in microhematuria in only one patient. Despite high age of the patients (mean age: 60.1 years) in this study, CNS (central nervous system) toxicities associated with ifosfamide and mesna treatment were minimal. The results suggested that the IAP combination therapy was effective and acceptable in the control of gynecological adenocarcinomas.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Doxorubicin; Drug Evaluation; Female; Genital Neoplasms, Female; Humans; Ifosfamide; Leukopenia; Mesna; Middle Aged; Remission Induction