Despite growing recognition that patient nonadherence with self-administered oral anticancer therapies is increasingly a key problem in clinical oncology, surprisingly little is known about what causes noncompliance or how best to intervene.

Recent evidence-based systematic reviews of the available research literature suggest that patient age and agent side effects each play a role in nonadherence—but no single risk factor or interventional silver bullet has been identified that applies to all oral agents, cancer types, or patient populations.

Until more is known, researchers advise clinicians to emphasize patient education, explaining to patients why adherence is important and discussing possible side effects.

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Oral anticancer agents are increasingly important in clinical oncology, representing more than 25% of oncology drugs that are in development or approved for use.1 Oral agents are central to the personalized oncology revolution, representing key targeted and maintenance therapies.

However, because these drugs are typically self-administered by patients at home, there is increasing concern about the effect of nonadherence to treatment plans.1-7 This can be a particular problem for agents that are most effective over long periods of time, such as imatinib maintenance therapy, which has potentially rendered chronic myeloid leukemia (CML) a chronic disease.1

Although most patients report that they prefer oral therapy to intravenous infusion therapy, studies suggest that nonadherence rates for oral agents can range as high as 84%, leaving adherence to oral therapies “a key issue in modern oncology treatment”.1,4

Despite this, in addition to evidence that nonadherence reduces an agent’s anticancer efficacy, surprisingly little has been established about what drives nonadherence or what can be done to improve adherence rates.1,4

Part of the problem is that research strategies and even researchers’ definitions and measures of adherence have not been standardized. For example, epidemiologists statistically control for potentially confounding or modifying factors in their multivariate analyses of nonadherence, but the specific factors controlled for in analysis vary from study to study.4 That complicates or precludes evidence-based meta-analyses where data from multiple studies are pooled for analysis.

All of the studies included in one recent systematic review “revealed methodological flaws”.4

Recent systematic reviews of the research literature indicate that, overall, lower-aged and elderly patients are less likely to comply with oral agent prescription guidance or treatment plans.1,4 Young women in particular may stop adhering with treatment plans for breast cancer when they wish to have children in the future and fear early menopause that may be triggered by treatment.1

RELATED: Adherence and CML: Overcome the Challenges to Taking Your Pills

Elderly patients often must manage multiple drugs with complicated dose scheduling, alongside failing memory and other comorbidities.1 Available evidence suggests that patients’ understanding of the role of oral therapies and patient ability to remember what they have been told, play an important role in nonadherence among elderly patients.2

One review, drawing on data from 25 published studies, also indicated that side effects were an important factor in patient nonadherence.1

Surprisingly, not all patients are warned about potential side effects associated with oral anticancer therapies.1,4 This likely contributes to interruptions in adherence when unanticipated toxicities occur. Patients should be educated about potential side effects and their manageability before oral therapy begins. Particularly among patients experiencing memory problems, caretakers and family members must be included in patient education efforts.2

There is some limited evidence that oral therapy patient education and support groups may improve adherence, though those findings await additional study and confirmation.2 Otherwise, few generalities are supported by the existing evidence base.1,4

Until more is known, treatment strategies and patient education should be tailored to a patient’s age, drug regimen, toxicity profile, memory problems, and social support.1

“Clinicians should help patients to understand that early recognition of treatment-related side effects can be of great benefit,” advised Mathieu Verbrugghe, MSc, and colleagues, of the Department of Public Health at Ghent University in Gent, Belgium.1 “Further, patients should be well informed about the long-term benefits of the treatment and how treatment-related side effects could be managed.”