Polypharmacy in View of Advances in Cancer Treatment

Advances in science have prolonged the average life span, and people are living relatively longer than before. Nevertheless, we have much to achieve to prolong the "healthy life span." People in old age suffer from multiple chronic ailments, and many of them succumb to death by heart disease, cancer, or stroke.[1] To survive these diseases, patients continuously depend on concurrent multiple medications—also referred to as polypharmacy—and with that comes the responsibility of appropriate selection, administration, and monitoring of therapeutic modalities. If drugs are used without proper evaluation of disease state, organ function, and concurrent therapies, such therapy may expose patients to life-threatening risks.

In her paper titled "Polypharmacy, Aging, and Cancer," Dr. Tam-McDevitt presents the overview of polypharmacy in geriatric patients, factors contributing to and consequences of its commonplace use, and recommendations to prevent its occurrence, highlighting its impact on an aging cancer population. This issue relates to the 37 million people—almost 12% of the total US population—who are over 65 years old and for whom cancer is the second leading cause of death, irrespective of gender or ethnic distribution.[1] These numbers will continue to rise, with millions of baby boomers soon entering this age group and posing a significant challenge for the safe and effective practice of medicine.

Impact of Aging

Aging is a steady process of physical, physiologic, psychological, and social changes. These changes influence both the treatment choices and the way the body responds to various treatments. The decline in organ function and comorbidities may alter the pharmacokinetic and pharmacodynamic behavior of drugs. Compromised cognitive function, memory, and visual and auditory senses, along with diseases (such as arthritis, which may cause difficulty in opening childproof drug containers) are some of the potential risk factors for noncompliance.[2] The extent to which these changes occur varies among individuals and results in a heterogeneous patient population with differential responsiveness to therapeutic modalities.

Causes of Polypharmacy

Dr. Tam-McDevitt has effectively described the factors contributing to polypharmacy. One of the prominent causes of polypharmacy is ineffectiveness or intolerability of existing treatment. Ineffectiveness of treatment for a long duration may prompt the patient to visit a new doctor, change the treatment, and take additional medicines, including prescription, over-the-counter, or herbal formulations, or dietary supplements. Also, it is more likely for a patient to miss a dose when it is not effective, resulting in noncompliance.

When the treatment is effective but has intolerable side effects, as with many anticancer drugs, the patient is kept on reduced doses and/or supportive care, and if that doesn't make the treatment tolerable, the patient may look for alternative drugs. The quest for better tolerated and effective therapies can inspire patients to attempt all available options that they perceive as safe, sometimes irrespective of lack of established knowledge. This makes them vulnerable to drug-drug or drug-supplement interactions, exposing them to unwarranted risks.

Targeted Therapies

In the past decade, treatment for cancer has seen significant changes. Advances in our understanding of molecular mechanisms underlying malignant transformation has shifted the focus of cancer drug discovery from development of conventional nonspecific cytotoxic drugs toward rationally designed targeted therapies with activity against cancer-specific pathways. These agents can better discriminate between normal and malignant cells, and hence, are less toxic, more effective, and show better compliance.[3]

For example, levels of bcr-abl tyrosine kinase enzyme are found to be selectively higher in patients with chronic myeloid leukemia (CML). Imatinib (Gleevec) was designed to specifically target this protein, and later proved to be efficacious. The drug is approved by the US Food and Drug Administration for Philadelphia chromosome–positive CML and also in Kit-positive gastrointestinal stromal tumors (GIST).[3]

Development of these types of treatments will help to minimize the occurrence of polypharmacy. Conversely, however, targeted monoclonal antibodies may sometimes be associated with rare but more serious side effects like gastrointestinal bleeding, infusion reaction, and hypertension, and proper caution should be practiced.[4]