US Pharm. 2019;44(6)HS-9-HS-12.

ABSTRACT: Oral chemotherapy has revolutionized oncology, yet with great advancement comes challenges. Oral chemotherapy medication adherence is a challenge for many patients and caregivers for many reasons, including side effects, finances, and lack of education and resources. Medication adherence is crucial in oncology to delay disease-free survival and progression-free survival. Pharmacists can help play a large role in educating patients and assisting them with issues related to oral chemotherapy. This article will discuss review papers and guidelines for oral chemotherapy adherence techniques, the role of the pharmacist, and resources to promote oral chemotherapy adherence.

Over the past couple of decades, oral chemotherapy drugs have forged a new therapeutic option, providing cancer patients with a more manageable, less invasive alternative to standard IV chemotherapy administration. The approval of capecitabine in 1998 initiated this new era of oral options, and within the next decade, more targeted agents such as imatinib, gefitinib, lapitinib, and nilotinib were approved. Within the future pipeline agents in the oncology landscape, it is estimated that 25% of the agents are planned in an oral formulation.¹

Approvals for these agents have been seen in several different types of cancer and have advanced to targeting specific genetic mutations.² This trend in convenient formulation has revolutionized oncology outcomes by significantly prolonging survival in patients who may have a poor prognosis, improving their quality of life, alleviating treatment burden, and imparting an element of patient treatment control.² The advancement has transitioned cancer care to resemble more of a chronic disease state instead of an acute disease state, relying on patients to be more responsible in the treatment paradigm.³

The High Stakes of Oncology Medication Adherence

Medication adherence involves a combined effort and silent understanding between healthcare providers and patients in regard to the degree of conformity in day-to-day treatment with respect to dosing and frequency, including the duration of therapy and discontinuation.² In a study that evaluated the difference in 6-year probability of major molecular response (MMR) with treatment of imatinib in chronic myeloid leukemia, the patient group with a 90% or higher adherence rate was associated with a 94.5% MMR compared with the patient group with less than a 90% adherence rate being associated with 28.4% MMR.² This significant difference in response to therapy demonstrates the importance in improving health outcomes, reducing disease progression, and improving tumor response.

The patient role in medication administration, therefore, is significantly more crucial when adherence to treatment regimens depends on proper self-management. Other challenges arise with the use of oral agents, such as patient safety and monitoring of adverse effects, since patients often would not be taking these oral agents in the inpatient/outpatient setting amid healthcare practitioners. Oral chemotherapy requires less oversight, symptom control monitoring, and support than standard chemotherapy infusions, leaving room for patients to miss doses and not stay as adherent to their treatment regimens. Research and data have shown that patients with cancer have reported lower rates of oral chemotherapy adherence, as low as 16%, compared with patients under the supervision of clinicians delivering infusion. Decreased adherence leads to poor outcomes, with an increase in morbidity and mortality, and underscores the importance of assessing medication adherence to oral cancer treatments, identifying barriers, and improving measures for patients to receive optimal outcomes from these novel agents.⁴

On the inpatient and outpatient side of oncology practices, studies have indicated that there is a lack of established protocols and procedures for documenting the prescribing of oral chemo agents, patient education, monitoring for adverse effects, and tracking patient adherence.² Surprisingly, there lies a gap with healthcare providers engaging in discussions and clinical documentation when evaluating chemotherapy administered intravenously versus patients taking oral agents. Developing strict and detailed patient monitoring plans, such as documenting office visit frequency and patient monitoring—whether weekly, monthly, or bi-monthly—frequent laboratory visits to monitor improvement markers, and even scheduled telephone calls from pharmacy departments can be implemented to foster a more dynamic patient-clinician relationship. Making improvements in this area holds the potential to directly improve not only medication adherence rates but, more importantly, survival rates.

Understanding Nonadherence Underpinnings

From a patient perspective, it may be of significant value to understand and determine whether underlying issues may be preventing them from staying adherent to their oral chemotherapy regimens. There are several forces that typically influence adherence rates with different disease states, and these apply to cancer patients. Some of these may include socioeconomic factors, such as cost and financial support, and therapy-related factors, such as intolerable side effects. Without supervision, these factors may incline patients to stray from taking their chemotherapy.

Healthcare providers and pharmacists have the ability to impact medication adherence rates in patients with cancer taking oral chemotherapy agents. Improved, more detailed pharmacy communication through counseling and monitoring may help patients feel more understood, therefore leading to open communication and strengthening clinician-patient relationships. Taking advantage of technology and developing strategies such as mobile applications, including self-reporting of adherence, adverse effects, alarm reminders, and self-reporting of mood and quality-of-life measures may also improve adherence rates and identify points when pharmacists can intervene. Clinicians need to understand the barriers in regards to medication adherence for patients taking oral chemotherapies, identify interventions to help overcome them to improve patient outcomes and reduce side effects, and explore areas where healthcare providers can play an integrative role in improving medication adherence.²

Oral Chemotherapy Medication Compliance

Oral administration can offer many advantages over intravenously administered chemotherapy, such as convenience and ease of administration. While these aspects of oral administration are favored, they also create the possibility of nonadherence because providers are unable to monitor compliance, since the patient no longer would have to come in to the infusion center for treatment. Because of this, it is becoming increasingly more important to assess nonadherence behavior and to address the disadvantages this can create for patients with cancer who are being treated with these agents. It is possible that these patients may be more motivated to be compliant, but many factors can still lead to adherence challenges.

A systematic literature review was conducted to assess adherence rates as well as methods of improving adherence. In this study, rates of adherence to these agents were as low as 46% for some patients. Other findings included an association of lower likelihood of response to therapy and higher mortality with poor adherence to oral antineoplastic therapy.² In a different study also assessing patients’ adherence to oral chemotherapy, it was found that 30% of the 125 participants reported some level of nonadherence.³

Various factors and barriers can lead to medication noncompliance. Nonadherence can be related to the patient, healthcare provider, or treatment itself (see TABLE 1).⁴ These reasons can include forgetting to take the medication on time, lack of accessibility to the medication, or not understanding directions. While there are many benefits to oral chemotherapy, completely controlling adherence is not possible, so these medications fall prey to these same barriers. Poor adherence to oral chemotherapy agents has been linked to poor outcomes, increased toxicity, and increased healthcare costs. Patient interventions, therefore, should be made to decrease the likelihood of nonadherence.

It is crucial to encourage and provide education to patients about the importance of remaining adherent to their medications as well as the associated risks. Counseling should include how to overcome the common barriers that lead to missed doses. Efforts from each healthcare member of a patient’s interprofessional team, including providers, pharmacists, and others, should strive to encourage patients to be adherent. With regard to patient-specific barriers, patient efforts to address forgetfulness can include setting daily routines to take medication, keeping medications where they will be noticed, or setting a reminder or alarm on their mobile device.

In today’s technological society, other options of increasing medication adherence have also become available. A study was done to create and evaluate the use of a mobile application and its ability to support patient adherence to oral chemotherapy. The application was composed of medication reminders, self-reporting of medication adherence and symptoms, an education library including nutritional information, Fitbit integration, social networking resources, and individually tailored symptom management feedback.⁵ Options such as this give promise to the emergence of different approaches that can be utilized to improve adherence.

Pharmacist’s Role in Oral Chemotherapy Compliance

Oncology pharmacy specialists (OPSs) have expert knowledge of anticancer medications. They offer a variety of services related to seven salient factors of medication management, including selection, procurement, storage, preparation/dispensing, prescribing, administration, and monitoring/evaluation/education.⁶ They also have extended their expert roles as frontline caregivers in supportive care issues such as nausea and vomiting, hematologic support, nutrition, infection control, and anticoagulants. Their roles are very important to maximize the benefit of drug therapy, minimize toxicity, reduce outpatient and inpatient hospital visits, and support successful oral chemotherapy adherence.  

According to the U.S. National Cancer Institute, antineoplastic oral agents now comprise as much as 25% of the 400 chemotherapy drugs due to their ability to reduce patients’ burden of care.⁶ Therefore, it is important for OPSs to help patients comply with oral chemotherapy drugs for improved overall survival, quality of life, and life expectancy. OPSs are well trained with drug-information skills that can aid in appropriate selection and provide medical information about antineoplastic pharmacology as well as dosage adjustment. They also contribute to the dosing aspects of the prescribing process to help manage drug therapy under physician supervision. In addition, they help procure available antineoplastics during manufacturing shortages.

Integrating Care for Better Adherence

The integrated pharmacy service provided by the OPSs, in collaboration with the specialty pharmacy, has greatly impacted patient medication adherence rates.⁷ This comprehensive service has also highlighted the variety of OPSs’ roles, such as preauthorization of prescriptions, third-party reimbursement, medication administration, and adverse side-effect management to enhance patients’ oral chemotherapy compliance.

Due to the high cost of oral oncolytics, OPSs control refills (instead of refills being requested by patients). They create a refill plan for patients at least 7 days before running out of medications through facilitating early assistance with prior authorization and providing direct involvement of support staff to assist with financial issues. This allows for assessing adherence, as well as preventing late refills and high nonfulfillment rates.⁸

In addition, OPSs establish weekly calling protocols for the first prescription cycle and then contact patients monthly to address their concerns about expected barriers, discuss strategies to overcome them, and inquire about missed doses, offering electronic reminders. With the ever-growing presence of smartphones, pharmacists can also utilize mobile patient counseling to empower efficacious adherence rates.⁴ OPSs initiate monthly assessment and counseling with a review of all the patients’ medications, including prescriptions, OTCs, vitamins, alternative therapy and herbal products, drug-drug interactions,  and potential side effects, along with supportive care medications and lifestyle modifications, such as contraception, diet, and fall-prevention precautions.^6,8

Patient education is paramount to support successful oral chemotherapy treatment.⁵ Proper handling, storage, taking drugs with or without food, and correctly disposing of hazardous waste are required for patients to know with oral chemotherapy treatment. Patients receiving oncology counseling and with the ability to talk to OPSs when the need arises are factors likely supporting successful oral adherence. The OPS is a vital member of an interdisciplinary team where nurses, oncologists, and primary care physicians work together  to provide the highest quality patient care.

Conclusion

Oral chemotherapy is a growing field and has revolutionized care for many oncology patients. With available resources, pharmacists can assist patients to promote oral chemotherapy adherence. It is vital that pharmacists educate patients, assisting with cost and using technology to support the patient in oral chemotherapy adherence. It is also imperative that in conjunction with physicians, patients are counseled on the risks of medication nonadherence. There are multiple resources available to pharmacists to help encourage patients to adhere to oral chemotherapy medications.

REFERENCES

1. Weingart SN, Brown E, Bach PB, et al. NCCN Task Force Report: oral chemotherapy. J Natl Compr Canc Netw. 2008;6(suppl 3):S1-S14.
2. Greer JA, Amoyal N, Nisotel L, et al. A systematic review of adherence to oral antineoplastic therapies. Oncologist. 2016;21(3):354-376.
3. Salgado TM, Mackler E, Severson JA, et al. The relationship between patient activation, confidence to self-manage side effects, and adherence to oral oncolytics: a pilot study with Michigan oncology practices. Support Care Cancer. 2017;25:1797-1807.
4. Partridge AH, Avorn J, Wang PS, Winer EP. Adherence to therapy with oral antineoplastic agents. J Natl Cancer Inst. 2002;94:652-661.
5. Fischbein JN, Nisotel LE, Macdonald JJ, et al. Mobile application to promote adherence to oral chemotherapy and symptom management: a protocol for design and development. JMIR Res Protoc. 2017;6(4):e62.
6. Ma CS. Role of pharmacists in optimizing the use of anticancer drugs in the clinical setting. Integrated Pharm Res Pract. February 2014.
7. Morgan KP, Muluneh B, Deal AM, Amerine LB. Impact of an integrated oral chemotherapy program on patient adherence. J Oncol Pharm Pract. 2018;24(5):332-336.
8. Mancini R, Wilson D. A pharmacist-managed oral chemotherapy program: an economic and clinical opportunity. Oncol Issues. 2012;27(1):28-31.

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