The use of alternative therapies in combination with cytotoxic chemotherapy is a potentially important clinical issue. Most patients assume that alternative therapies are harmless since they are not drugs and, thus, do not have an established track record of toxicities. In fact, these agents are generally unregulated, and their lack of toxicity has generally not been confirmed in any large-scale clinical trials.
Drs. Labriola and Livingston concentrate on the specific issue of antioxidants and their potential to interfere with the DNA-damaging actions of cytotoxic agents. I prefer to look at this problem in more general terms. First of all, it is critical to recognize that antioxidants and related alternative therapies are drugs, regardless of whether or not they are normally present in the human body (and, thus, could potentially be considered nutrients). The toxicity of vitamin A, clearly a nutrient, has been well described. An analogous group of natural therapies are the cytokines, some of which (ie, interleukin-2) are viewed by most oncologists as being highly toxic.
Pharmacokinetic and Pharmacodynamic Interactions
In approaching the general issue of drug interactions, one has to consider the potential for both pharmacokinetic and pharmacodynamic interactions. Pharmacokinetic interactions result in an alteration in drug elimination (clearance) and, thus, can result in patient exposure to unexpectedly high or low plasma concentrations. The retinoids have the potential to induce their own metabolism, as well as the metabolism of other agents. On the other hand, the flavonoids have the potential to inhibit the metabolism of chemotherapeutic drugs, particularly if both the flavonoid and the drug are taken orally.
Drs. Labriola and Livingston focus their discussion on the potential pharmacodynamic interactions between antioxidants and DNA-damaging agents. They speculate that antioxidants may inhibit the cellular effects of selected cytotoxic agents, while acknowledging that there are sparse data to guide clinical practice.
Complex Dilemma for the Practitioner
The dilemma for the practicing oncologist may be complex. In my own practice, I emphasize to patients that alternative therapies are drugs and, as such, complicate the administration of highly toxic therapies. I also stress that the administration of any drug, even a natural compound, has the potential to increase the side effects of cancer chemotherapy. In my experience, this warning usually results in patients avoiding alternative therapies, especially during the critical perichemotherapy period.