With the increasing prevalence of oral cancer drugs, underadherence — patients missing doses — has been concern. But overadherence, the other side of the coin, can also be a problem, especially when the dosing regimen is complicated.
In fact, in a study published online October 10 in the Clinical Journal of Oncology Nursing, researchers found that when patients had problems with adherence to oral chemotherapy or targeted agents, they were more likely related to overadherence than underadherence (20% vs 13%).
In addition, overadherence was more common in patients with breast cancer than other types of cancer, likely because of the complex therapeutic regimens associated with breast cancer treatment.
Overadherence can be a significant clinical problem because it can lead to increased drug-related adverse effects, life-threatening toxicity, and discontinuation, all of which can reduce the effectiveness of treatment, according to the study authors, led by Sandra L. Spoelstra, PhD, RN, assistant professor of nursing at Michigan State University in East Lansing.
Patients Become Confused
Most clinicians are aware that that the more complex the medication regimen, the higher the risk for nonadherence, the researchers note. Many of the oral oncolytics have complex regimens in which the dosing and timing of pill administration matter, and that often involve cycles of days on and days off or pill increases and decreases.
The result is that patients can become confused about to when they are supposed to begin and end their treatment, which can inadvertently lead to overadherence, the researchers explain.
Keeping Patients on Track
But there are steps that clinicians can take to help patients adhere to their treatment regimens. Dr. Spoelstra advises providers to speak to patients about their treatment in a "nonconfrontational" manner.
"Pharmacists often use motivational interviewing," rather than the traditional "talking to" model that physicians and nurses use, she told Medscape Medical News.
She pointed out that in a literature review of 64 medication adherence interventions in older adults, 3 focuses of intervention were found to be effective: patient factors (such as patient education, motivation, and behavior); medication factors (such as symptoms); and administration (such as complexity).
"We do not have standardization of care when patients initiate oral-agent treatment for cancer," Dr. Spoelstra said. "Most patients on IV chemo go to classes to learn how to manage, and interact at clinics with RNs when it is administered. Patients on oral agents do not have as much time with RNs or MDs."
"Instead, there is often minimal instruction when starting care or when symptoms become more severe, and there may be delivery issues or their pharmacy may not have the drug in when they need it," she explained.
Dr. Spoelstra acknowledged that it can be difficult for clinicians to monitor adherence effectively. "We only have self-report, pill count, and pharmacy dispensing records," she explained. "Unless it is a drug with a biologic marker of some sort, like a blood draw for levels, you cannot have absolute proof it is taken. Almost all providers are having difficulty identifying the date patients start on oral-agent regimens and are now tracking that for quality purposes."
Addressing patient concerns better could help improve adherence, she continued. For example, patients need to understand how and when to take their medication, whether rest periods are involved, how much the medication costs, how to get financial help if it is needed, and how to handle the pills (safety issues).
"If a patient misses a dose, should they double up, skip, or call their doctor? And when do they call the doctor about symptoms? If symptoms get worse, should they continue taking their pills?" Questions like these need to be answered, said Dr. Spoelstra.
Another issue that pertains to some of the oral agents is polypharmacy. It is important to examine a patient's drug profile to make sure there are no drug interactions that need to be avoided, she added.
Adherence Issues
Adherence to oral chemotherapy can be problematic for a number of reasons, as previously reported byMedscape Medical News, including cost, patient motivation, and the relationship between patient and provider.
In a review of oncolytic studies that Dr. Spoelstra coauthored, underadherence rates ranged from 20% to 80% (Semin Oncol Nurs. 2011;27:116-132), but less is known about overadherence to oral chemotherapy agents.
In a previous study conducted by Dr. Spoelstra's team, 42% of 119 adults with solid tumors were nonadherent at 10-week follow-up. The researchers found that missed doses increased with regimen complexity, and that higher rates of adherence were related to lower levels of symptom severity (Cancer Nurs. 2013;36:18-28).
Second Analysis
Their current overadherence study was a longitudinal secondary analysis of data from 100 patients from the original sample. The majority of the cohort was white and female, and most patients had breast, lung, or colon cancer.
The most commonly used oral agents were capecitabine (Xeloda), erlotinib (Tarceva), lapatinib (Tykerb), imatinib (Gleevec), temozolomide (Temodar), and sunitinib (Sutent). In addition, 25% of the cohort was receiving concurrent intravenous chemotherapy.
There was no significant difference in patients who were adherent, overadherent, or underadherent after adjustment for age, sex, race, study group, baseline symptom severity, or depression score.
However, patients with breast cancer were more likely to be overadherent (n = 15) than those with colon or rectal cancer (n = 4) or other cancers (n = 1).
Complexity of regimen significantly affected adherence (P < 0.01), as did type of drug cycle (P < .01).
There was an association between symptom severity and overadherence, but it was not statistically significant because of a lack of power, the researchers report. They note that patients might "self-modulate" after symptoms occur by skipping 1 or more doses, and then double-up on doses after the symptoms resolve, leading to overadherence.
Instances of overadherence were more often related to severe symptoms, and instances of underadherence were more often related to less severe or fewer symptoms. "Clinically, this makes sense as symptoms often are caused by the chemotherapy, so if too much chemotherapy is taken (when overadherence occurs), symptom severity would be higher," they conclude. "Consequently, the potential for adverse events from toxicity caused by overadherence may lead to medication stoppage, which makes adherence to the prescribed treatment regimen difficult."
The authors have disclosed no relevant financial relationships.
Clin J Oncol Nurs. Published online October 10, 2013. Abstract
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