Vincristine in Combination Therapy of Cancer: Emerging Trends in Clinics

SIMPLE SUMMARY: Vincristine is a vinca alkaloid naturally occurring in Catharanthus roseus. It belongs to antimitotic compounds, which arrest the cell cycle via disrupting microtubule dynamics. This property makes vincristine a useful compound in anticancer therapies, however, due to its unspecific biological action, vincristine causes severe side effects, mainly neurotoxicity. Nevertheless, at low concentrations, it is still a beneficial and widely used drug in combinatorial regimens of cancer treatment. Most commonly, it is administered with cyclophosphamide, doxorubicin, and prednisone but also with methotrexate or procarbazine, and dacarbazine. Currently, anticancer research focuses on targeted therapies and the development of antibodies specific to cancer cells. An example of such a drug combination broadly used in clinics is vincristine and rituximab, an antibody binding cancer cell surface receptor CD20. Combining vincristine with monoclonal antibodies is an emerging approach, which has been currently evaluated in clinical trials. This review article reports on the most commonly used vincristine-based drug combinations and summarizes currently running clinical trials. The number of ongoing studies shows that vincristine has its stable place in anticancer therapies and despite all its limitations, it has remained an essential part of anticancer therapies. ABSTRACT: Treatment of blood malignancies and other cancer diseases has been mostly unfeasible, so far. Therefore, novel treatment regimens should be developed and the currently used ones should be further elaborated. A stable component in various cancer treatment regimens consists of vincristine, an antimitotic compound of natural origin. Despite its strong anticancer activity, mostly, it cannot be administered as monotherapy due to its unspecific action and severe side effects. However, vincristine is suitable for combination therapy. Multidrug treatment regimens including vincristine are standardly applied in the therapy of non-Hodgkin lymphoma and other malignancies, in which it is combined with drugs of different mechanisms of action, mainly with DNA-interacting compounds (for example cyclophosphamide), or drugs interfering with DNA synthesis (for example methotrexate). Besides, co-administration of vincristine with monoclonal antibodies has also emerged, the typical example of which is the anti-CD20 antibody rituximab. Although in some combination anticancer therapies, vincristine has been replaced with other drugs exhibiting lesser side effects, though, in most cases, it is still irreplaceable. This is strongly evidenced by the number of active clinical trials evaluating vincristine in combination cancer therapy. Therefore, in this article, we have reviewed the most common cancer treatment regimens employing vincristine and bring an overview of current trends in the clinical development of this compound.