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ALTHOUGH THE ADVENT of oral anticancer therapy has many benefits for patients, monitoring and assessing treatment adherence can be a challenge. But it's a challenge that nurses must meet because suboptimal dosing can lead to disease recurrence or progression, and overmedication can cause toxicity. This article discusses how nurses can maximize clinical outcomes and minimize adverse reactions through education and adverse event management during therapy.
Oral chemotherapeutic agents such as cyclophosphamide and methotrexate have been available in clinics for decades, but with the advent of hormonal and targeted therapies, the number of oral chemotherapeutic options has increased sharply in recent years.1,2 As of 2011, 35% of all pipeline anticancer drugs were projected to be oral formulations, with the upward trend likely to continue.1,3,4
Targeted oral anticancer therapies interfere with the growth process specific to cancer cells-for example, HER2 (human epidermal growth factor receptor 2) or tyrosine kinase inhibitors-making them less likely to harm normal cells. Thanks to these new therapies, many cancer types are now managed as chronic conditions.
Targeted oral therapies typically cause fewer adverse reactions than chemotherapies, but not always: In at least one study of 1,987 patients, adverse reactions such as hand-foot syndrome and hyperbilirubinemia were 6.6 and 2.5 times more frequent, respectively, in patients receiving oral therapy (capecitabine), compared with parenteral therapy (5-fluorouracil).4
Like all medications, oral anticancer drugs have both benefits and drawbacks for patients. (See Pros and cons of oral anticancer therapies).4-6 For example, oral drugs are convenient and easily administered at home. Requiring fewer trips to the healthcare facility compared with drugs administered I.V., oral therapies offer patients more flexibility and independence. Additionally, unlike cytotoxic chemotherapies, targeted therapies are intended to treat only malignant cells, so patients generally have fewer adverse reactions and a better quality of life.1,4,6
But achieving the optimal use of oral agents can be a challenge.1,2,4-6 Patients might have difficulty recognizing and managing adverse drug reactions, drug-food interactions, or drug-drug interactions without a healthcare provider's (HCP's) supervision. Oral agents can also be subject to patient variability in gastrointestinal (GI) absorption, leading to differences in pharmacokinetics and pharmacodynamics and, potentially, GI discomfort.4 Other major concerns include self-administration safety because HCPs are no longer present to monitor treatment administration and support patient adherence and persistence.
Adherence (formerly called compliance) refers to how well patients conform to their prescribed or recommended treatment-for example, taking the right drug dose at the right time. Nonadherence may result in either over- or undermedication. In contrast, persistence refers to the overall length of time that patients remain on their prescribed or recommended treatment (from the start date to the end date, regardless of whether the end date is due to an interruption in therapy or cessation of treatment).7,8
When patients with cancer are treated with parenteral anticancer drugs, they report to the clinic where HCPs can consistently monitor their responses over the course of treatment. Consequently, both adherence to therapy and persistence are high, contributing to the effectiveness of treatment.4
Because oral therapies are considered easier to administer, you might expect adherence and persistence rates to be as good as, if not better than, those associated with parenteral therapies. However, this paradigm doesn't always transpire in ambulatory care settings, raising major concerns for clinicians.1
The concerns stem from the fact that the therapeutic benefits of anticancer treatments depend largely on whether patients maintain their therapy regimen exactly as prescribed.1,2 This is particularly important when targeted oral therapies are used in patients with metastatic disease to prevent disease progression, as in adjuvant treatment following tumor resection or in patients with chronic diseases such as chronic myelogenous leukemia (CML), because patients may need to continue treatment for years or indefinitely.1,9-11 Nonetheless, despite the demonstrated benefits of oral anticancer agents and the recognized importance of treatment adherence on recurrence-free survival and overall survival, low adherence with oral therapies remains common.2,5,11-16
Many factors relating to the patient, treatment, environment, and/or clinician have been found to affect adherence to oral anticancer therapies (see Factors that contribute to nonadherence).1-3,6,11 For example, patients who are forgetful or cognitively impaired or who have a history of mental illness are more likely to be nonadherent.1,2,5,11 Similarly, patients with comorbidities (such as diabetes or hypertension) that require additional medications may become nonadherent as their treatment regimen becomes more complicated.1 Moreover, adverse events (AEs), drug-drug interactions, and drug-food interactions can be a major issue, especially when patients aren't prepared for them and don't know how to manage their symptoms.2,4,6 Citrus fruit (grapefruit in particular) and pomegranate have been reported to interact with many oral targeted agents in oncology.17
Complicated dosing patterns (for example, a specific time of day, multiple times a day, or "4 weeks on/2 weeks off" types of scheduling) can also impede adherence,1,2 as can the duration of the treatment: the longer the treatment, the less likely a patient is to remain adherent.9 A study of 8,769 women with breast cancer who took hormonal therapy showed that overall adherence rates declined to 49% by year 4.5, consistent with a 7% to 10% increase in discontinuation or nonadherence for every year of daily oral therapy received.15 Additionally, the HCP's belief regarding the efficacy of the treatment provided and his or her relationship with the patient (quality of communication and after-care management) may affect the patient's attitude toward the treatment and influence adherence.1,2,6,11
Some oral anticancer medications are costly. Although virtually all of them are included on formularies and covered by insurance companies, co-pays and deductibles can still be substantial, causing difficulties in filling prescriptions and a financial burden for the patient.1 The high cost of treatments may drive patients to adopt the "some is better than none" mentality, leading to reductions in the quantity or frequency of the regimen. Medicare Part D patients may also be vulnerable to the "donut hole" and be less adherent from January through March when out-of-pocket limits haven't been met and full coverage hasn't yet started.
Several methods are available to monitor adherence to oral anticancer therapies, but none is optimal (see Methods available to monitor adherence). Some are still too expensive for widespread use; for example, microelectronic monitoring devices that record the date and time the cap on a medication container is removed. Others (such as patient questionnaires, diaries, and pill counts) are subject to errors or variability (for example, variable serum drug levels).1,2,18 Measuring blood levels of medication, metabolites, or other markers may reveal only recent adherence without representing long-term behavior.
How can nurses help improve adherence to oral anticancer therapies and ensure optimal treatment efficacy when direct observation isn't feasible? This is a critical issue because uncertainty about a patient's adherence to the prescribed treatment might cause the HCP to wonder if the lack of response reflects true treatment resistance or nonadherence, which in turn could lead to efficacy or safety issues.1,2,7
Because nurses interact with patients during every visit, they can improve patient adherence rates by encouraging communication, ensuring regular follow-up, engaging family members, and providing tools to facilitate monitoring at home. Nurses should tell patients that if they miss doses or don't take them at the same time every day, the amount of drug in their system will be lower than needed to be effective, which can keep them from benefiting from it.
Nurses need to develop and implement practical strategies to help their patients adhere to treatment (see Checklist of strategies to improve adherence to treatment). For example, nurses should encourage frequent, honest communication between the patient and the members of the multidisciplinary team. They should identify opportunities, provide tools to promote communication, talk about the importance and benefits of a team approach to the patient, and use lay language. In addition, nurses should reiterate the importance of taking oral medication exactly as prescribed and explain why taking the right dose at the right time directly affects the quality of the results patients get with oral therapy. Nurses also need to repeat and reinforce the HCP's dosing instructions, the goals of the therapy, and what can be expected from the treatment.
Web-based programs have been developed to help patients and clinicians address problems in real time. The STAR (Symptom Tracking and Reporting) program, for example, is designed to be readily accessible and inexpensive to implement, and securely stores data in a quickly retrievable form.19 Patients can describe their adverse reactions as they experience them (instead of waiting for the next visit to the clinician), using any web-enabled computer. In response, clinicians can review and interpret the symptoms sooner and address the issue immediately.
Nurses should use routine monitoring, follow-ups, and phone calls to engage patients, review their progress, monitor and reinforce adherence, and address their individual needs and concerns. They must encourage patients to discuss any difficulties they're having with their medication and assess those who aren't achieving expected therapeutic results for potential nonadherence.
Nurses can encourage good self-care habits and identify ways for patients to maintain adherence throughout their entire course of treatment by making the dosing regimen as simple as possible (especially for patients who take additional medications to manage adverse reactions or treat comorbidities), creating individual dosing plans, and assisting them in organizing medications and daily dosing schedules if needed.
Adverse events such as fluid retention, fatigue, and GI symptoms are a main reason why many patients don't adhere to their prescribed regimen.1-3,11 Nurses can increase their positive impact on adherence by educating patients about what AEs to expect, how to manage them, and when and how to report them.
In one study assessing adherence to a capecitabine regimen in patients with metastatic breast or colon cancer, the most important finding was the inability of patients to identify and report signs and symptoms of toxicity.6 Nurses should proactively help patients manage AEs by asking specific questions about any symptoms they may be experiencing. This should be done at therapy initiation and during every follow-up visit or phone call because patients may not know how to recognize AEs or raise the issue.
The use of imatinib in the treatment of gastrointestinal stromal tumors (GISTs) is a case in point. GISTs represent the most common type of mesenchymal tumor of the GI tract. Imatinib is an oral targeted therapy approved as first-line therapy for the treatment of unresectable and metastatic GIST, and as adjuvant therapy following resection of primary GIST.20 Imatinib has a simple daily regimen (once daily in most cases) and adverse reactions are usually mild to moderate in nature and manageable.9,17,18,21 Interruption of treatment has been shown to result in rapid disease progression in both settings.21-27
Despite the compelling evidence about the benefits of imatinib, an analysis of prescription-filling activity in 4,043 patients with GIST or CML showed that overall adherence didn't exceed 75% and that persistence averaged only 255 days over 2 years.24
Oral anticancer therapies can greatly improve patient survival and quality of life, but they're effective only if patients adhere to their prescribed treatment regimen. A multidisciplinary approach involving physicians, surgeons, pharmacists, and nurses is a vital component for successful outcomes.
Because of their critical role in patient care, nurses can raise patients' awareness about potential AEs and the importance of reporting them in a timely fashion, which will help increase adherence as well. By doing so, nurses can help patients realize optimal therapeutic benefits from oral anticancer therapies and improve their overall quality of life.
1. Screen patients for adequate food intake (which affects drug absorption) and gut function, as well as motivation regarding commitment, reliability, and physical limitations.
2. Encourage and facilitate communication with the multidisciplinary team. Web-based programs such as the STAR program let patients report AEs in real time from anywhere; such programs should be implemented in all cancer centers.
3. Emphasize the benefits of good habits, including adherence to treatment and persistence.
4. Promote routine monitoring and encourage patients not to miss appointments.
5. Schedule frequent follow-ups (face to face, phone calls, emails) to discuss difficulties, assess results, and review goals. Use web-based programs that facilitate real-time communication of difficulties and questions.
6. Teach patients to incorporate self-care into their daily routine.
7. Educate patients about proactive management of AEs. Even mild AEs can have a negative impact on patients' quality of life when experienced over a long period. Instruct patients to contact their nurse or HCP whenever they experience severe AEs, as they may need to stop therapy to avoid safety issues.
8. Engage patients and family members in understanding the disease, treatment, adverse reactions, potential drug-drug or drug-food interactions, and the risks and benefits of therapy. Provide educational material (videos, booklets) and abbreviated methodologies; follow up with calls to review methodologies and understanding.
9. Educate patients about adherence and encourage questions and candor. Emphasize that poor adherence, if undetected, can be misinterpreted as insufficient/inadequate medication and lead to improper changes in treatments, limiting future options.
10. Highlight the efficacy of the oral therapy compared with parenteral alternatives, and address any misconceptions patients may have about their drug. For example, explain that oral anticancer therapies are real therapies and may cause serious adverse reactions.
11. Provide tools to facilitate dose management and monitoring at home-for example, written instructions, pillbox, calendar, cell phone/text reminders, diary, financial assistance, and social support groups.
12. Simplify dosing. Poor adherence typically reflects regimen complexity rather than patients' resistance to therapy.
13. Consider providing short-term prescriptions; clinicians may lose contact with patients if they have an extended medication supply. However, patients may request money-saving longer-term mail orders for prescriptions, and some drugs may be dispensed only in preset numbers/amounts, or may not be stocked in regular pharmacy chains and must be obtained from specialty pharmacies.
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