Low-grade serous ovarian cancer with BRAFV600E mutation treated with metronomic chemotherapy — a case report and literature review

Introduction. Ovarian cancer (OC) is the leading cause of cancer death worldwide. In Poland, it is the fourth leading cause of death from neoplasms in women. OC is a heterogeneous disease with low-grade cases characterized by a better prognosis, but poor chemosensitivity. Metronomic chemotherapy (MC) may be a beneficial approach.  Case presentation. We present a patient with low-grade serous ovarian cancer (LGSOC) with long-term disease control achieved with MC despite being resistant to standard-dose chemotherapy with paclitaxel and carboplatin. Overall survival (OS) of the patient was 65 months. MC was administered most of the time. The patient was treated with two metronomic regimens: topotecan plus cyclophosphamide and vinorelbine plus methotrexate, both in combination with hormone therapy. The cancer was found to harbor the BRAFV600E mutation (v-raf murine sarcoma viral oncogene homolog B1, a valine-to-glutamic acid substitution at position 600), but that did not impact the treatment.  Conclusions. LGSOC has distinct features from high-grade serous ovarian cancer (HGSOC). MC may be a valuable option in LGSOC despite being understudied. The BRAFV600E mutation occurs in 2–33% of low-grade serous ovarian tumors. It is a more common finding in LGSOC than in HGSOC. BRAF inhibition in OC may be a new therapeutic option. Some BRAF inhibitors have already been registered for solid tumors with this mutation

Metronomic chemotherapy based on Topotecan or Topotecan and cyclophosphamide combination (CyTo) in advanced, pretreated ovarian cancer

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 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