Ifosfamide and mesna in previously treated advanced epithelial ovarian cancer: Activity in platinum-resistant disease

Purpose: There is a critical need to find new antineoplastic drugs that are active in platinum-refractory ovarian cancer. We conducted a phase II trial of single-agent ifosfamide with mesna uroprotection in patients with ovarian cancer previously treated with an organoplatinum compound to assess its activity in this clinical setting. Patients and Methods: Ifosfamide (1.0 or 1.2 g/m²/d for 5 days, delivered on a monthly schedule) was administered to the 57 patients entered onto this trial. Dose reductions were permitted for unacceptable toxicities. Results: Toxicity included severe bone marrow suppression (WBC count < 1,000/μL and/or platelet count < 50,000/ μL), renal dysfunction (serum creatinine level > 2.0 mg/dL), and reversible CNS dysfunction (disorientation, hallucinations, somnolence, and agitation), which occurred in 20%, 14%, and 12% of patients, respec- tively. Of 41 patients with strictly defined platinum-refractory ovarian cancer, five (12%) demonstrated a partial (four) or complete (one) response to this treatment program. Conclusions: Single-agent ifosfamide has modest but unequivocal activity in platinum-resistant ovarian cancer. Further studies of this drug used as a front-line agent along with an organoplatinum compound or as part of a dose-intensification program with bone marrow, peripheral stem cell, or colony-stimulating factor support are indicated. In addition, single-agent ifosfamide is a reasonable standard second-line treatment strategy in appropriately selected patients with platinum-refractory ovarian cancer.