Metronomic Chemotherapy Based on Topotecan or Topotecan and Cyclophosphamide Combination (CyTo) in Advanced, Pretreated Ovarian Cancer

Simple Summary In this retrospective analysis of 72 advanced ovarian cancer patients, we have evaluated the safety and activity of orally-administered metronomic chemotherapy (MC) based on single agent topotecan or a combination of topotecan and cyclophosphamide (CyTo regimen). In this difficult population, metronomic chemotherapy demonstrated a clinically meaningful activity and good safety profile. The MC provided a clinical benefit in the majority of treated patients, with fewer than 15% not benefitting from this treatment (biochemical or radiographic progression). The median PFS in the whole population was 3.65 months, but the median PFS in patients with a biochemical response to MC (18.2% of patients) reached 10.7 months. The study also showed that overweight or obese patients had significantly better outcomes on MC than patients with BMI Patients with advanced ovarian cancer (OC) have a detrimental prognosis. The options for systemic treatment of advanced OC in later lines of treatment are limited by the availability of active therapies and their applicability to often fragile, exhausted patients with poor performance status. Metronomic chemotherapy (MC) is a concept of a continuous administration of cytotoxic drugs, which is characterized by multidirectional activity (anti-proliferative, anti-angiogenic, and anti-immunosuppressive) and low toxicity. We have performed a retrospective analysis of consecutive, advanced, chemo-refractory OC patients treated with MC based on single-agent topotecan (1 mg p.o. q2d) or on a topotecan (1 mg q2d) and cyclophosphamide (50 mg p.o. qd) combination (CyTo). Metronomic chemotherapy demonstrated promising activity, with 72% and 86% of patients achieving biochemical or objective disease control and 18% and 27% of patients achieving a biochemical or objective response, respectively. The median PFS in the whole population was 3.65 months, but the median PFS in patients with a biochemical response to MC (18.2% of patients) reached 10.7 months. The study also suggested that overweight or obese patients had significantly better outcomes on MC than patients with BMI <25 kg/m(2). This article is the first report in the literature on metronomic chemotherapy based on a topotecan + cyclophosphamide combination (CyTo). The CyTo regimen demonstrated safety, clinical activity, and potential broad clinical applicability in advanced OC patients and will be evaluated in a forthcoming clinical trial.