Cyclophosphamide or ifosfamide in patients with advanced and/or recurrent endometrial carcinoma: a randomized phase II study of the EORTC Gynecological Cancer Cooperative Group

Currently, available chemotherapy regimens for patients with advanced or recurrent endometrial cancer are generally not curative. Thus, there is a need to identify more active single agents in this disease. In this study patients pre-treated and not pre-treated with first line combination chemotherapy were entered into a randomized phase II study of either cyclophosphamide (CYCLO) or Ifosfamide (LFOS). Patients and method: Sixty one eligible patients with recurrent or metastatic histologically proven, adenocarcinoma of the uterine corpus entered the study. The median age at entry was 62 (range 40-74) years. Twenty patients (33%) had prior hormonal treatment and 31 (51%) prior chemotherapy. CYCLO was given at a dose of 1200 mg/m(2) and IFOS at a dose of 5 g/m(2). Both drugs were administered i.v. over 24 hours on day one every three weeks. Adequate pre- and post hydration as well as use of Mesna in the Ifosfamide arm were mandatory. Results: A median of two treatment cycles (range 1-12) per patient were given. In the chemotherapy-naive patients, in the CYCLO arm two PRs (RR 14%, C.I. 2-43%) were seen and in the IFOS arm two CRs, two PRs, (RR 25%, C.I. 7-52%) were observed. No responses were seen in pre-treated patients. The duration of responses were: 15(+), 7(+) months for the CRs, 15(+) and 5 months for PRs in LFOS arm and 67(+), 4 months in CYCLO arm. The hematological toxicity was dose-limiting and similar in both treatment arms. No serious non hematological toxicities were reported, but a transient increase of the creatinine blood level was seen in two IFOS patients (6%). Conclusion: Ifosfamide is an active drug in the treatment of chemotherapy-naive patients with advanced endometrial cancer and its application in currently used (combination) regimens should be considered. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.