With conventional chemotherapy treatment delivered intravenously, and administered by medical personnel in health care facilities, the potential risks include infected IV access lines and extravasations that can cause skin and tissue damage. An increasing number of oral chemotherapy agents (OCAs) are now available; these medications reduce the inconvenience of being tethered to an IV line and eliminate trips to the hospital or outpatient infusion centers for admixture and administration of chemotherapy.¹

For clinicians considering OCA treatment, proper management is crucial, as patient nonadherence can hamper treatment effectiveness and may lead to a high risk of toxicity and increased utilization of health care resources.² Patient- and treatment regimen-associated factors, as well as cost, can affect adherence. Pharmacists must assume a proactive role in addressing these concerns to improve patient adherence to OCA treatment.

The Importance of Adherence

Medication adherence requires a collaborative approach to decision-making (see SIDEBAR), ideally with mutual agreement with respect to medication choice, dosing, and frequency, between the patient and the clinician.³ Among all disease states, studies show nonadherence rates of approximately 50%, while adherence rates for patients on chemotherapeutic medications are extremely variable, and have been cited as low as 16% and as high as 100%.^3,4 Adherence is directly tied to disease-free survival and overall survival; clinically significant findings show associations between nonadherence and cancer progression, longer inpatient stays, lower survival rates, and higher expenditures on health care resources.³

Determining Patient Eligibility for OCA Treatment

The pharmacist plays a critical role in evaluating whether an oral agent is an option for a patient by confirming that the drug and indication are appropriate. Thereafter, it can be determined if the patient is able to tolerate oral administration.⁵ Patient-specific factors to evaluate include the individual’s comorbidities, health literacy, and financial concerns. Medication-associated factors, including dose, indication, regimen, and frequency, must be considered. The efficacy and safety of OCA treatment, in conjunction with patient preference and cost, are primary considerations. Patient preference is important, as adherence and satisfaction increase if the patient buys in to OCA therapy.

Factors that Affect OCA Adherence

Patient Factors

OCA adherence can be affected by the patient’s emotional and mental health, physical health and comorbid conditions, as well as access to or lack of a strong social support network.⁶ The treatment regimen and side effects also may directly impact patient adherence. For example, dose rounding can reduce the patient’s pill burden, making adherence more likely.

Cost and Reimbursement Factors

The increased cost of oral agents compared with IV therapy, as well as the decreased coverage of OCAs, can impact out-of-pocket expenditures and contribute to poor adherence.⁷ Because OCA reimbursement is considered part of the patient’s drug plan, it may be associated with significant copays. It is not uncommon to encounter copays as high as $5,000 for a monthly OCA supply.¹ Data demonstrates that high costs can adversely affect access and adherence to OCAs.⁸

Strategies for Increasing OCA Adherence

Pharmacists can help facilitate access and adherence to OCA treatment by employing motivational interviewing, implementing electronic reminders, exploring cost control options, providing supportive patient and family education, implementing the use of monitoring techniques, and conducting medication reconciliation.

Motivational Interviewing

In its 2016 oral adherence toolkit, The Oncology Nursing Society (ONS) describes the difference between traditional counseling and motivational interviewing.⁹ Motivational interviewing encourages the health care provider to establish a partnership with the patient in developing the treatment care plan.⁹ When employing this collaborative model, the health care provider shares information with the patient, rather than simply telling the patient what to do. Gaining the patient’s buy-in is more likely when the patient is involved in their own care.

Interviewing should include clear information on how to take the OCA to minimize side effects (eg, whether to take the OCA with or without food), as well as a discussion of possible food and drug interactions.

Electronic Reminders

Electronic reminders can be deployed to improve OCA adherence. For example, cell phone alarms, text message reminders, smart phone applications, automated voice recording reminders, and glowing or electronic pillboxes are all viable options.¹⁰

Controlling Costs

When considering OCA treatment, it is critical to determine the cost to the patient prior to initiating use. Copays may vary depending on the type of pharmacy that dispenses the medication; dispensing sites may include community retail pharmacy, mail-order pharmacy, practice- or physician-dispensing pharmacy, hospital pharmacy, or specialty pharmacy. Consider that patients may experience mail-order OCA dispensing as a less personal option, given that the patient’s interaction with the oncology pharmacist or nurse case manager must occur remotely, usually via telephone.

Most pharmaceutical companies have patient-assistance programs that assist with copays; in some cases, patients may be able to start OCA treatment at no cost.

Patient and Family Education

Improving adherence to OCA treatment is contingent on effective patient and family education. The pharmacist should present their services as a resource to patients and their families throughout OCA treatment and be available to answer questions and assist in minimizing side effects that may occur. Pharmacists should make patients aware of the potentially dire consequences of nonadherence. Sharing information about the severity of the condition and highlighting the benefits of treatment will help to overcome barriers and ensure patients take their medications as prescribed.¹¹

Medication Calendar and Diary

The pharmacist should assist in creating a medication schedule and encourage use of a medication diary to record OCA treatment, as well as any observed physiological changes that occur. These resources should be personalized to each patient’s OCA schedule.

For example, trifluridine and tipiracil (Lonsurf) indicated for metastatic colorectal cancer is dosed as 35 mg/m2 twice daily on days 1 to 5 and days 8 to 12 of a 28-day cycle. The medication schedule for this OCA can be customized so that the patient initiates therapy on a Monday, which improves adherence; it is easier for the patient to remember that the doses will be taken Monday through Friday, with the weekends off, for 2 weeks, and then wait for 2 weeks prior to beginning another 28-day cycle.

Monitoring Techniques

Organizations may choose to implement medication-monitoring techniques to maximize adherence, including evaluation of refill records, measuring serum drug concentrations, and utilizing microelectronic monitoring systems.¹² These techniques can be particularly useful when patients are part of clinical trials that require strict adherence among participants.

Moreover, monitoring may be an option when managing patients receiving oral tyrosine kinase inhibitors to avoid adverse effects from excessive doses, which can be reflected in plasma concentration levels. Therapeutic dose monitoring can also be used to adequately assess clinical response, which will enable the provider to switch patients from imatinib to nilotinib or dasatinib when necessary in order to achieve a prompt clinical response.¹³

Medication Reconciliation

Medication reconciliation by pharmacy helps prevent duplication in therapy, drug interactions, and unnecessary indications, and also presents an opportunity to provide counseling and answer patient questions, which is especially important when an OCA comes from a mail order facility. In addition, medication reconciliation can help prevent hospital readmissions and reduce unnecessary prescriptions, thus increasing medication affordability and reducing costs.¹⁴

Conclusion

As oral chemotherapy treatment becomes more common, robust management will be critical to effective care. As the medication experts, pharmacists are responsible for managing OCA therapy and helping to eliminate barriers to access. Improving OCA adherence is essential to ensuring patient safety and achieving the best possible therapeutic outcomes.

C. Nnamdi Nzelibe, PharmD, BCOP, was a hematology/oncology research pharmacist at Sinai Hospital of Baltimore from 2006 through October 2017, and is currently employed as a research pharmacist at the Anne Arundel Medical Center in Annapolis, Maryland. He received his doctorate in pharmacy from Howard University in Washington DC. Nnamdi’s professional interests include hematology/oncology pharmacy and investigational drug services.

Adenike Uchenna Omoyosi, BS, MPH, 2018 PharmD Candidate, a researcher for various private and federally funded studies, has a BS in nutrition from The Ohio State University and an MPH from Mercer University. She is currently pursuing her Doctorate of Pharmacy from Howard University College of Pharmacy. Adenike’s career goal is to own and operate international health clinics that offer pharmaceutical services.

References

1. Boodman SG. Cancer Patients’ Dilemma: Expensive Pills Vs. Invasive Chemo Treatment. Kaiser Health News. April 27, 2010.
2. McCue DA, Lohr LK, Pick AM. Improving adherence to oral cancer therapy in clinical practice. Pharmacotherapy. 2014;34(5):481-494.
3. Greer JA, Amoyal N, Nisotel L. (2016) A systematic review of adherence to oral antineoplastic therapies. Oncologist. 2016;21(3):354-376.
4. Ruddy K, Mayer E, Partridge A. Patient adherence and persistence with oral anticancer treatment. CA Cancer J Clin. 2009;59(1):56-66.
5. Jin JF, Zhu LL, Chen M. The optimal choice of medication administration route regarding intravenous, intramuscular, and subcutaneous injection. Patient Pref Adherence. 2015;9:923-942.
6. Johnson LA. Factors influencing oral adherence: Qualitative metasummary and triangulation with quantitative evidence. Clin J Oncol Nursing. 2015;19(3 suppl):6-30.
7. Nelson R. Oral chemotherapy poses financial burden to patients. Medscape. amcp.org/workarea/downloadasset.aspx?id=10434.
8. Dusetzina SB. Drug pricing trends for orally administered anticancer medications reimbursed by commercial health plans, 2000-2014. JAMA Oncology. 2016;2(7):960-961.
9. Oncology Nursing Society. ONC Oral Adherence Toolkit. www.ons.org/practice-resources/toolkits/oral-adherence. Accessed November 6, 2017.
10. Burhenn PS, Smuddle J. Using tools and technology to promote education and adherence to oral agents for cancer. Clin J Oncol Nurs. 2015;19(3 suppl):53-59.
11. Atreja A, Bellam N, Levy SR. Strategies to enhance patient adherence: Making it simple. MedGenMed. 2005;7(1):4.
12. Weingart SN, Brown E, Bach PB. NCCN Task Force Report: Oral Chemotherapy. J Natl Compr Canc Netw. 2008;(6 suppl 3):S1-S14.
13. Miura M, Takahashi N. Routine therapeutic drug monitoring of tyrosine kinase inhibitors by HPLC-UV or LC-MS/MS methods. Drug Metab Pharmacokinet. 2016;31(1):12-20.
14. Bertsch NS, Bindler RJ, Wilson PL, et al. Medication therapy management for patients receiving oral chemotherapy agents at a community oncology center: A pilot study. Hosp Pharm. 2016;51(9):721-729.