Polypharmacy in View of Advances in Cancer Treatment

August 1, 2008

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.

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]

Personalized Medicine

Dr. Tam-McDevitt also discusses the complex problem of altered physiology coupled with comorbid conditions and use of multiple medications. To effectively manage this issue, significant efforts have been directed toward identification of the clinical, genetic, and molecular markers that can be used to identify the best treatment for a group of patients based on their characteristics.

Biomarkers may also help in early assessment of therapeutic benefits (stratification of responders and nonresponders) or occurrence of toxicities. For example, UGT1A1*28 has been established as a valid genetic biomarker for UGT1A1 activity and increased irinotecan toxicity, and is measured in addition to clinical markers (eg, bilirubin levels) in treating patients with irinotecan.[5]. Similarly, the levels of molecular markers like epidermal growth factor receptor (EGFR), which is differentially overexpressed in many solid tumors, is used to assess the effectiveness of biologics like cetuximab (Erbitux).[3]

Apart from these markers, protein and genomic signatures have also been identified to examine the susceptibility to[6] and progression of disease,[7] and for prediction of therapeutic outcomes[8] and resistance to treatments.[9] Such individualized therapy obviates the patient's exposure to noneffective treatment and associated side effects, which helps in limiting the perpetual cycle of therapy followed by adverse events and then a new therapy, and so on, which Dr. Tam-McDevitt has pointed out as a serious problem. Thus, personalized medicine is an important tool in the physician's arsenal and can help in controlling the occurrence of polypharmacy. We have seen many recent developments in this area, and much more along these lines should be forthcoming in the near future.

Drug-Drug Interaction and Adverse Drug Reactions

With the use of multiple medications and coexisting medical conditions, older cancer patients are at increased risk for medication-related problems such as drug-drug, drug-disease, drug-food, and drug-supplement interactions as well as adverse drug reactions. A patient's medical history and current prescribed treatments should be carefully examined to avoid the possibilities of such interactions.

The creation of an electronic dispensing record (EDR) is one approach to getting quick access to a patient's complete medical history, which remains available to patient, physician, nurse, and pharmacist around-the-clock, via a secured website.[10] This allows real-time updates of medical records including input from the patient concerning use of alternative (herbal) medicines, and its interoperability improves communication between and/or among physicians, pharmacists, nurses, and patient. The EDR provides easy access to updated information about each medication, including contraindications and medication recalls, and also checks for any potential drug-drug interactions as soon as drugs are prescribed.[10] These dynamic features help in deciding on the appropriate drugs and doses for individual patients, avoiding therapeutic duplication errors and limiting the occurrence of drug-drug interactions, adverse drug reactions, and the resulting sequence of polypharmacy.

Other alternatives like electronic drug-drug interaction charts also serve as quick reference for identification of interactions among prescribed drugs. These technologies should be routinely used to maximize the benefits of polypharmacy.

Conclusions

In conclusion, we agree with Dr. Tam-McDevitt's recommendation that recognition of polypharmacy by active participation of physician, nurse, and pharmacist is the key to preventing its occurrence. Doctors must obtain the complete medical history of patients and should actually examine the medications they are taking-also knows as the "brown bag assessment"[11]-before prescribing the new medications. Preference should be given to drugs with wide therapeutic windows and medication guidelines for elderly patients (eg, Beers criteria should be considered while making treatment decisions). To ensure patient compliance, drugs with simplified dosing regimens should be selected,[11] and prescribers should make sure that before beginning treatment, the patient completely understands the associated benefits and risks.

In addition to these essentials, parallel developments in medical record handling techniques and prognosis and treatment of cancer should be implemented in patient care. If available, predictive markers should be used to make rational treatment decisions. Individualization of therapy based on pharmacogenomics should be encouraged. These advances in cancer management complement conventional treatment strategies for older cancer patients, and integration of these into clinical practice is critical for maximizing the ratio of benefit to risk with polypharmacy.

-Lokesh Jain, MS
-William D. Figg, PHARMD

Financial Disclosure: The authors have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

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The main article can be found here:
Polypharmacy, Aging, and Cancer: Growing Risks

References:

References
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