The introduction of oral chemotherapy shifted the model of cancer treatment. The benefits of oral versus IV chemotherapy include increased patient convenience, patient empowerment (as patients play an active role in their treatment), the ability to modify dosing to control for potential toxicities at any point during treatment, less frequent office and hospital visits, and significantly shorter medication administration times.¹

Conversely, when therapy is self-administered by patients in their homes, problems involving medication delivery and administration, which in a hospital environment would be managed by health care professionals, can become magnified. Therefore, robust management of oral chemotherapy programs and effective patient education are critical.

A Pharmacist-Led Monitoring Program
John Dempsey Hospital (JDH) is the hospital for the University of Connecticut health care system and is home to the only full-service emergency department in the Farmington Valley. Accredited by The Joint Commission, JDH has been named as a top performer in the care of patients with heart failure, heart attack, pneumonia, and surgery and has centers of excellence in geriatrics, maternal-fetal medicine, cardiology, cancer, and orthopedics.

JDH treats hospitalized patients with cancer on the oncology inpatient floor and provides outpatient chemotherapy services for approximately 20 to 30 patients per day in its 14-chair outpatient cancer center. Recently, the cancer center moved to a new outpatient pavilion, allowing for an increase in the number of patients served. As a state hospital, JDH also provides chemotherapy services for inmates housed by the department of corrections. Oral chemotherapy is playing an increasingly significant role in the health care system’s cancer treatment armamentarium, as it offers a non-invasive option for patients who prefer to receive chemotherapy in the comfort of their homes.

In 2012, JDH implemented a pharmacist-led, oral cancer therapy-monitoring program. This program includes oral chemotherapy education, medication therapy management, adherence monitoring, toxicity monitoring and management, and management of related supportive care issues. Patients are followed either collaboratively with the medical oncologist during scheduled clinic visits, through clinic visits with the oncology pharmacist alone, by telephone contact, or by email contact. After implementation of the pharmacist-led monitoring program, the overall number of interventions per patient increased. These interventions include addressing adherence and drug-drug interactions, altering therapy, assisting with cost-related issues, managing adverse events, and providing medication information. Adherence to oral cancer therapy lab parameter monitoring, which is important to assess for toxicity and dose adjustments, has increased as well. These outcomes highlight the benefit and necessity of such a program, especially considering that since 2012, JDH’s use of oral chemotherapy has doubled.

Safe Use of Oral Chemotherapy
Just as patients must be educated about the oral treatments they receive, health care professionals also must be educated about the proper handling, storage, and administration of these agents, in addition to monitoring patient adherence to their prescribed oral chemotherapy regimens.

Accidental exposure to oral chemotherapy can occur at multiple points in the medication-use process, including during transport, unpacking, storage, handling, administration, and disposal; as such, effective strategies to reduce exposure are vital. Health care providers must be properly trained, stay abreast of developments in the field, and adhere to discipline-specific guidelines when handling oral chemotherapy.² Important strategies to reduce exposure to oral chemotherapy include²:

• Store cytotoxic agents in a designated area per the manufacturer’s instructions, separate from noncytotoxic agents. Some oral chemotherapies are air-, moisture-, and/or light-sensitive, so be sure to follow storage specifications
• Institute correct use of PPE
• Do not dispense oral chemotherapy using automatic counting machines
• Perform manipulations, including compounding, crushing, cutting, and splitting, in a biological safety cabinet (BSC) using appropriate PPE
• Use separate equipment for cytotoxic and noncytotoxic agents
• Regard all disposable PPE and garb as cytotoxic waste and dispose according to local waste disposal regulatory guidelines. Wash or decontaminate all nondisposable materials exposed to chemotherapeutic agents, including counting trays, tools, and surfaces
• Appropriately train all clinical staff who may come in contact with oral chemotherapies, including pharmacists, pharmacy technicians, nurses, clerks, hygiene workers, and sanitation personnel

The Importance of Education
JDH’s oncology pharmacist works closely with the oncologists in the outpatient setting. Once the oncologist and patient have met to determine a treatment plan, the oncologist notifies the oncology pharmacist, who then provides the appropriate information to the patient about their oral chemotherapy in the clinic room. The oncology pharmacist, often accompanied by pharmacy students (when on campus) or a pharmacy resident, provides patients with information on appropriate handling, administration, adherence, toxicity issues, side effects, and disposal. The education plan typically includes family and caregivers, based on the patient’s ability to assume responsibility for managing therapy.

It is important to keep in mind that patient education materials must be appropriate for the patient/caregiver’s literacy level and understanding. Documentation of educational sessions should include patient feedback reflecting engagement and understanding of the materials provided.

Specific topics covered in oral chemotherapy education should include:

• Goals and duration of oral chemotherapy
• Efficacy and toxicity information
• Storage, handling, preparation, administration, and disposal information
• Concurrent cancer treatment and supportive care medications/measures (when applicable)
• Possible drug/drug and drug/food interactions
• A plan for missed doses or when vomiting of a dose (spillage) occurs
• Common and serious side effects of oral cancer therapy
• For pregnant or breastfeeding patients, a risk/benefit assessment of oral chemotherapy
• Explanation of which side effects should prompt patients to immediately notify their physician for dose or other adjustments
• Allergy assessment
• Procedure for discontinuation of oral cancer therapy

Discussing common and rare side effects of oral chemotherapy treatment with the patient is particularly important. While typical side effects of oral chemotherapy vary by medication and patient, oral agents can cause side effects similar to those associated with IV chemotherapy, including nausea, vomiting, diarrhea, hair loss, mouth sores, skin changes, and low blood counts.³ In addition, certain side effects, such as rashes and other dermatologic reactions, are more common with oral chemotherapy. Side effects unique to oral chemotherapy include hand-foot syndrome, fatigue, flu-like symptoms, and nail changes.⁴

Oral chemotherapy agents comprise nearly half of all new chemotherapy drugs in development,^5,6 so keeping abreast of the adverse effects of newer medications is critical. For example, the drug abiraterone can cause hypokalemia and edema, so it must be taken concomitantly with prednisone to minimize these toxicities. Thus, patients must be educated about why the two drugs are coadministered.

In addition, patients are provided with a packet of information to take home that includes instructions for appropriate handling and disposal. Finally, patients are encouraged to contact the pharmacist or oncologist with any questions.

Although oral chemotherapy is considered by many to be less toxic than IV chemotherapy, this is not the case.² An educational program for staff must emphasize that oral agents are as toxic as their IV counterparts and must be handled as hazardous drugs. Moreover, all stakeholders should adhere to established guidelines and standard operating procedures that are specific to their practice.²

Patient adherence to oral chemotherapy treatment is essential to successful outcomes. Suboptimal adherence may result in disease or treatment complications, including disease progression and premature death.⁵ Health care providers must monitor and identify barriers to adherence and develop strategies to promote and ensure proper drug administration. Factors that may hinder adherence include long treatment periods, complex schedules, and high cost (see SIDEBAR).⁶

There are several direct and indirect ways to monitor patients’ adherence to therapy⁷:

• Serum Drug Levels. Measuring patients’ serum drug levels is an accurate way to measure adherence; however, acceptable ranges often are unknown, and assays may not be widely available.
• Refill Records. Monitoring patients’ refill records provides objective data, but does not measure actual intake.
• Self-Report. Asking patients if they have been taking their medication as prescribed is a quick way to gauge adherence; however, patients tend to overestimate adherence.  
• Patient Medication Diaries. Having patients keep medication diaries is inexpensive and actively involves the patient in treatment; however, diary keeping can be time consuming.
• Microelectronic Event Monitoring System (MEMS). A MEMS provides accurate data indicating when a patient opens a medication bottle, but is often not feasible and can be expensive.

Due to the complexities of the MEMS and serum drug level monitoring, many institutions, including JDH, rely on patient self-reporting, as well as monitoring refill records. Regardless of the monitoring method chosen, developing and maintaining a collaborative relationship between the patient and the health care team is critical to promoting adherence.

Conclusion
Oral chemotherapy offers patients important advantages, including greater convenience, empowerment, and fewer trips to the health care facility, but the benefits only can be realized with careful attention to safety and monitoring. All health care providers who handle these medications must remain current and knowledgeable about side effects and guidelines governing safe handling, storage, and administration. Perhaps most importantly, collaborative relationships between health care providers and patients, as well as appropriate patient education, are necessary to ensure proper management and adherence.

Jay M. Patel, PharmD, received his pharmacy degree from the University of Connecticut School of Pharmacy. At the time of writing this article, he was a PGY1 pharmacy resident at John Dempsey Hospital. Jay is now pursuing a PGY2 oncology pharmacy residency at Yale New Haven Hospital.

Christopher Niemann, PharmD, is the oncology clinical coordinator at John Dempsey Hospital.

References

1. Elizabeth McGann, DNSc, RN. Promotion Adherence to Oral Chemotherapy. An Expert Interview with Susan Moore, RN, MSN, AOCN, and Debra Winkeljohn, RN, MSN, AOCN, CNS. Medscape. June 9, 2011. http://www.medscape.com/viewarticle/744303. Accessed June 3, 2015.
2. Goodin S, Griffith N, Chen B, et al. Safe handling of oral chemotherapeutic agents in clinical practice: recommendations form an international pharmacy panel. J Oncol Pract. 2011;7(1):7-12.
3. American Cancer Society Web site. Oral Chemotherapy: What You Need to Know. http://www.cancer.org/treatment/treatmentsandsideeffects/treatmenttypes/chemotherapy/oral-chemotherapy. Accessed June 1, 2015.
4. Mayo Clinic Web site. Living with Cancer Blog: Oral Chemotherapy—Not Just Any Ordinary Pill. http://www.mayoclinic.org/diseases-conditions/cancer/expert-blog/oral-chemotherapy/bgp-20056402. Accessed June 1, 2015.
5. Given BA, Spoelstra SL, Grant M. The challenges of oral agents as antineoplastic treatments. Semin Oncol Nurs. 2011;27(2):93-103.
6. Bosley C. What Affects Patient Adherence to Oral Chemotherapy? ONS Connect: The Official News Magazine of the Oncology Nursing Society. http://connect.ons.org/issue/april-2012/a-closer-look/what-affects-patient-adherence-to-oral-chemotherapy. Accessed June 1, 2015.
7. Geynisman DM, Wickersham KE. Adherence to targeted oral anticancer medications. Disc Med. 2013;15(83):231-241.

SIDEBAR
Cost Impacts Accessibility and Adherence
The difference in cost between IV and oral chemotherapy can be significant and, thus, can influence patient access to treatment. Traditional chemotherapy, administered intravenously, is covered under a health plan’s medical benefit; patients often are responsible for a low copay or sometimes pay nothing at all for the medication. Conversely, oral chemotherapies are typically covered under a health plan’s pharmacy benefit, often resulting in higher out-of-pocket expenses.

In some cases, a patient’s inability to pay for the drugs may affect adherence. The pharmacist, together with other members of the multidisciplinary care team, plays an important role in ensuring these patients have access to medications and in assisting with any cost-related issues that arise. This is accomplished by working with insurance companies to get the drug approved for dispensing, as well as enrolling patients in assistance programs offered by the drug’s manufacturer. Because orally administered chemotherapeutic agents tend to have a narrow therapeutic index, strict adherence to administration schedules and dosing is required. Therefore, patients with a history of nonadherence to their oral medications should be excluded from oral chemotherapy treatment. In addition, consider excluding patients with significant oropharyngeal disability, significant gastrointestinal problems (eg, fistulae), bowel obstruction, and geriatric patients with dementia or depression, all of which may limit a patient’s oral intake.

References
Nelson R. Oral Chemotherapy Poses Financial Burden to Patients. Medscape. May 7, 2009. http://www.medscape.com/viewarticle/702522#vp_1. Accessed June 5, 2015.