Phase II trial of imatinib mesylate in patients with recurrent platinum- and taxane-resistant epithelial ovarian and primary peritoneal cancers

Objectives. To evaluate the efficacy and tolerability of imatinib mesylate (Gleevec; Novartis Pharmaceuticals, Basel, Switzerland) in patients with recurrent ovarian and primary peritoneal cancer. Methods. This was an open-label, single-institution phase II trial. Patients were eligible if they had measurable platinum/taxane-resistant disease, received 2-4 prior treatment regimens, and over-expressed at least one imatinib target (c-Kit, PDGFR-β, or c-Abl) by immunohistochemistry. Imatinib was administered orally at 600 mg daily for 6 weeks (one course) and was repeated in the absence of measurable progression. Results. Sixteen enrolled patients were evaluable for toxicity and 12 for response. The median number of prior treatments was 4. A total of 29 courses were initiated. No complete or partial responses were documented during a median follow-up of 6.6 months. However, 4 (33%) of the 12 evaluable patients had stable disease lasting 3.8, 6.4, 7.5, and 8+ months. Expression of PDGFR-β and c-Abl was seen in 15 (94%) and c-Kit in 8 (50%) patients' tumors. There was no relationship between best response (stable disease) and target expression. Adverse events were uncommon, with fatigue and nausea/vomiting being reported in 34% and 31% of cycles, respectively. Two patients underwent dose reduction for rash and edema (n = 1) and grade 3 neutropenia (n = 1). No grade 4 toxicity was observed. Conclusion. Imatinib mesylate was well tolerated but did not produce clinical responses in patients with previously treated metastatic ovarian and primary peritoneal carcinoma.