A retrospective, real-life analysis of metronomic oral single-agent cyclophosphamide for the treatment of platinum-pretreated advanced ovarian carcinoma in Italy

Abstract

Introduction Metronomic oral cyclophosphamide (MOC) presents many potential advantages, such as significantly less severe side effects than standard regimens, ease of administration, and the delivery of a dose-dense but not necessarily dose-intense treatment. These observations prompted us to evaluate in a retrospective, multicenter study the efficacy and toxicity of MOC in a real-life series of pretreated cancer patients. Methods The study is a multicenter, retrospective analysis of the activity of single-agent MOC in patients with recurrent or residual epithelial ovarian, fallopian tube, or primary. Eligible patients were continuously treated with MOC at 50 mg/day until progression, toxicity, or death. Overall response rate (ORR), stable disease (SD), and disease control rate (DCR) were reported. Results The study included 62 patients. Three patients reached a complete response rate (5%), 11 had a partial response rate (18), and 15 had stabilization of disease (24) for an ORR of 23% and a DCR of 47%. Patients with low-grade indolent tumors showed an ORR and an SD rate higher than that observed in non-indolent ones (33% vs. 18% and 28% vs. 14%, respectively). Overall, progression-free survival was 3.5 months (range 1–9 months). Conclusion Single-agent MOC is active and very well tolerated in a significant fraction of patients with refractory, recurrent, or residual epithelial ovarian, fallopian tube, or primary peritoneal cancer. In the vision of a practical approach, single-agent MOC may be a useful palliative treatment option for patients with poor tolerance to high-dose regimens or widely pretreated. Further studies are needed better to characterize the role of such an approach in clinical practice.

A review and metanalysis of metronomic oral single-agent cyclophosphamide for treating advanced ovarian carcinoma in the era of precision medicine

“…These data align with those recently reported by our group in 62 patients, with exciting activity, especially in indolent ovarian cancer. 40 Interestingly, a significant percentage of patients showed a stabilization disease, even if short-lasting. A recent exhaustive review and meta-analysis on the activity and toxicity of all schedules and combinations of MOC for recurrent or platinumrefractory EOC reported an ORR and DCR of 25% (95% CI 12-41) and 61% (95% CI 43-77), respectively, and a median PFS exceeding 4 months (95% CI 2.62-5.97) and a median OS of (95% CI 2.62-5.97) and 11.26 months (95% CI 8.13-14.39).…”

Siklofosfamid kaynaklı doku hasarında Nrf2/Keap1 sinyal yolağının borik asit ile modülasyonunun in silico olarak değerlendirilmesi

“…CP'nin kronik uygulama dahilinde kullanılan metronomik dozunun müsinöz ve epitelyal yumurtalık kanserleri, sarkom, akciğer ve prostat kanserleri de dahil olmak üzere çeşitli tümör tiplerinde etkinlik gösterdiği belirlenmiştir [6]. Hatta metastatik meme karsinomunda bile hafif bir toksisite artışı ile hastalık palyasyonunda önemli sonuçlar alınmıştır [6][7][8][9].…”