Vinca Alkaloid Toxicity

Vinca alkaloids, which belong to a class of cell cycle phase M specific anti-tubulin agents, are one of the first plant alkaloids to be developed for use as anti-cancer agents in humans. This class of drugs derived from Vinca rosea (Catharanthus roseus) consists of first-generation (vincristine, vinblastine) and second-generation semi-synthetic derivatives (vinorelbine, vinflunine, and vindesine). Vinflunine, the newest fluorinated anti-microtubule agent, has been advocated to have a higher potency and lesser frequency of adverse events when compared to the older agents. They are usually used in combination with other chemotherapeutic agents (as part of multi-drug combination regimens) since they have been shown to potentiate the anti-cancer effects of these agents and are also known to be well tolerated with manageable adverse effects. These agents are highly lipophilic and attain very high intracellular concentrations, making overproduction of P-glycoprotein, which is an efflux transporter protein, a plausible mechanism of development of acquired drug resistance. Mutations in beta-tubulin with overexpression of different isotypes have also shown to correlate with the production of altered drug effects, leading to the development of resistance.