Gp. Sutton et al., PHASE-II STUDY OF IFOSFAMIDE AND MESNA IN REFRACTORY ADENOCARCINOMA OF THE ENDOMETRIUM - A GYNECOLOGIC-ONCOLOGY-GROUP STUDY, Cancer, 73(5), 1994, pp. 1453-1455
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.