Vincristine in Combination Therapy of Cancer: Emerging Trends in Clinics

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.

Keywords: antibodies; antimitotics; combinatorial treatment; cyclophosphamide; dacarbazine; doxorubicin; etoposide; procarbazine; topotecan; vinca alkaloids.

Figure 1

Chemical structure of vincristine.

Figure 2

Vincristine binds the β-subunit of a tubulin dimer on the boundary with a neighboring dimer and, thus, stabilizes the microtubule dynamics by preventing binding free tubulin dimers to the microtubule fiber.

Figure 3

Chemical structures of cyclophosphamide, doxorubicin, vincristine, and prednisone (together forming the CHOP regimen) and etoposide (with CHOP forming the EPOCH regimen).

Figure 4

Phases of the cell cycle, which are affected by vincristine, and the compounds, which are used in combination with vincristine in cancer treatment.