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

Abstract

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/m2. 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.

A phase II study of a doublet metronomic chemotherapy regimen consisting of oral vinorelbine and capecitabine in Chinese women with HER2‐negative metastatic breast cancer

“… 30 Owing to the diverse antitumor mechanisms of metronomic chemotherapy, a growing number of studies are currently endeavoring to integrate metronomic chemotherapy with other interventions, including targeted therapy and immunotherapy, among others, for the purpose of treating tumors. 31 , 32 , 33 , 34 , 35 In recent years, metronomic chemotherapy has gained widespread application in a range of cancers, including BC, 36 , 37 esophageal and gastroesophageal cancer, 38 lung cancer, 39 pancreatic cancer, 40 ovarian cancer, 41 and others. The current regimen utilized the oral metronomic chemotherapy approach with a combination of drugs, with the advantages of convenient drug administration and higher pharmacoeconomic efficiency compared with intravenous administration.…”

Strikingly high activity of metronomic chemotherapy in a patient with locally advanced, life-threatening cutaneous squamous-cell cancer — case report and discussion of the literature

“…Metronomic chemotherapy is a reasonable therapeutic approach in many patients with advanced, non-rapidly proliferating cancers, especially those who are elderly or have significant comorbidities [6][7][8][9][10][11][12]. The oral-intravenous approach presented in this article represents smart combined chemotherapy designed to activate all possible mechanisms of the cytotoxic drugs used.…”

Metronomic chemotherapy and drug repurposing: A paradigm shift in oncology

“…Multiple targeted modalities or traditional chemotherapeutics such as taxanes and platinum compounds were used in combination and were found to have synergistic effects. Additionally, new therapeutic approaches are used to treat illnesses, including biological molecules, medications, and immune-based therapies [ [14] , [15] , [16] ]. Traditional chemotherapy medicines have different administration regimens, and toxicity profiles, including antitumor activity from molecularly targeted therapies [ 17 ].…”