Addressing Inaccurate Cancer Chemotherapy Drug Dosing
Personalized Cancer Care
The oncology field still reports the lowest treatment efficacy rate of any of the major medical therapeutic areas.
Cancer is a very complex disease. In fact, it is not one disease, but rather a broad group of various diseases and mutations, compounding the challenges of effective treatment and cure. This is all the more reason the medical community should utilize the tools available as effectively as possible.
Many of the recent breakthroughs in improving the effectiveness of cancer chemotherapy treatment have come from a “personalized medicine” approach. Personalized medicine is the tailoring of medical treatment to the individual characteristics of each patient rather than the “one-size-fits-all” approach of the past. Much focus in personalized medicine has been placed on understanding a person’s unique molecular and genetic profile. This information can be used to predict what makes them susceptible to certain diseases or to predict which medical treatments will be safe and effective for each patient, and which ones will not be beneficial. These are remarkable and clinically significant advancements.
However, although pharmacogenomics can provide the patient’s genotype, it cannot present the patient’s phenotype. The phenotype more accurately guides the specific drug dosage necessary to achieve the desired optimal drug exposure for the best therapeutic effect with minimal toxicities. This is because many factors besides genetic regulation impact drug absorption and clearance. These include disease stage, organ function, age, race and drug-drug interactions, among others. These factors can result in inter-patient blood level variability greater than 10-fold.
Chemo Dosing Today
The most common method of dosing for cancer chemotherapy drugs is body surface area (BSA). BSA still represents the old “one size fits all” approach to patient care in this age of personalized medicine. This method of dosing, which takes into account only the patient’s height and weight, was derived in 1916 based upon the study of only eight patients as a means of estimating the conversion of drug doses in animals to human doses. There is no rigorous scientific basis for the use of BSA with cancer drugs. In fact, there is growing scientific evidence that this approach is invalid and results in high inter-patient variability in drug absorption and clearance. This means that if two patients are given the same dose based on body surface area, the concentration of the drug in the bloodstream over time in one patient may be 10 times higher or lower than in the other patient. This variability was demonstrated with 14 common chemotherapy drugs. This figure shows the wide variability in clearance found in the study.
Felici A, Verweij J, Sparreboom A. Dosing strategies for anticancer drugs: the good, the bad and body-surface area. Eur J Cancer. 2002;38:1677–1684.
Numerous clinical studies have demonstrated that variability in drug exposure can lead to high variability in the efficacy of chemotherapy treatment and the side effects that are associated with cytotoxic drugs. Therapeutic drug monitoring (TDM) has been shown to reduce variability in drug exposure.
- If the drug concentration is too low, cancer cells may become resistant and there is a higher risk of poor treatment outcomes. The ideal situation is to administer the right amount of drug that will result in the optimal exposure for the individual patient.
- If the drug concentration is too high, the patient may suffer from severe toxicity. This impairs treatment and reduces patient’s quality of life and can lead to side effects that last long after treatment.