Chemotherapy safety: Why, when, and how (Proceedings)

Apr 01, 2010

Chemotherapy safety can be broken down into two big categories: safety for the patient, and safety for the individuals handling the drugs. Understanding how chemotherapy works provides a background for knowing potential dangers of treatments as well as how to safely use these beneficial drugs.

General principles of chemotherapy

Chemotherapy damages (and in some cases kills) cells that are growing and dividing rapidly. The extent of damage is determined by the dose of drug and the length of time that the cells are exposed to the drug (efficacy = dosage x time). Cancer patients have 3 main populations of cells that may be affected by chemotherapy.

      1. Tumor cells: Genetic instability and rapid growth of tumors create an inherent sensitivity to chemotherapy-induced DNA damage. Rapidly dividing cells are more likely to be damaged by chemotherapy than quiescent cells, but this depends upon the mechanism of action of each specific chemotherapeutic.

     2. Intestinal epithelial cells: It takes 3-5 days for the intestinal epithelial cells lining the crypts to mature and migrate up to the villi tips. Chemotherapy-induced damage to these cells takes 3 to 5 days to manifest.

     3. Bone marrow: Cells with the shortest half-life (neutrophils and platelets) are of most concern. Nadirs (the low point in the cell count) most often occur at 7 days post-therapy.

Patient safety

Chemotherapy toxicities are categorized as general or specific. General side effects can occur with any chemotherapy drug. They occur in rapidly dividing normal tissues. Most chemotherapy protocols used in veterinary medicine have < 5% incidence of severe side effects. Most side effects are self-limiting and will resolve with minimal vet intervention.

General side effects that may be seen

GI toxicity

There are 2 mechanisms by which this can occur, in either situation it is manifested as inappetance, nausea, vomiting, and/or diarrhea.

     1. Direct damage to intestinal epithelial cells. Onset is 3 to 5 days after therapy, paralleling the time it would take for cells to migrate out of the crypts and onto the villi.

     2. Triggering of the chemoreceptor trigger zone, either directly (onset immediate or w/i 24 hrs) or through stimulation of gut vagal efferents (from GI damage).

If the patient has a history of chemotherapy induced emesis, use antiemetics (metoclopramide, odansatron, etc.) prior to and following drug administration.