Gary Plank, PharmD

There is a need for continued adverse event management for patients receiving oral chemotherapy due to the high incidence of adverse events and discontinuation rates. Pharmacists play a unique role in helping patients manage complicated dosing regimens, drug interactions, and adverse event profiles of oral chemotherapy.

As an increasing number of oral chemotherapy agents are developed, patients are being required to take on more responsibility and play a larger role in the treatment of their disease. Pharmacists play a unique role in helping patients manage the complicated dosing regimens, drug interactions, and adverse event profiles of oral chemotherapy. There is a need for continued adverse event management for patients receiving oral chemotherapy due to the high incidence of adverse events and discontinuation rates.

The National Cancer Institute (NCI) reports that 25% of the 400 anti-neoplastic agents in the FDA pipeline are planned to be oral medications.

 Advantages of oral chemotherapy include patient convenience, prolonged exposure to the medication, reduced inpatient and ambulatory patient care costs, and improved quality of life.

 According to a survey by Liu et al,3 90% of palliative care patients preferred oral rather than intravenous chemotherapy.

Challenges of oral chemotherapy include drug interactions, adherence concerns, toxicity profiles, and fewer encounters with health care providers, which all reinforce the need for increased patient education regarding oral chemotherapy.

 Patient education is the foundation of successful oral chemotherapy treatment.

 In a survey of 42 national cancer centers, few centers had systems established for monitoring or managing risks associated with oral chemotherapy. Additionally, clinicians at 36 of the 42 cancer centers expressed concern regarding the risks associated with oral chemotherapy.

Patients who receive oral chemotherapy commonly experience adverse drug events that cause therapy interruptions, dose reductions, and a negative impact onquality of life. Lau et al

 reported that the top 5 adverse events in oncology patients are constipation, nausea/vomiting, fatigue, alopecia, and drowsiness. This project also reported that 88% of the most common adverse drug reactions in oncology patients were predictable, and approximately 50% were possibly preventable.

Appropriate patient education is vital in preventing adverse events associated with oral chemotherapy. Numerous oral chemotherapy agents have complicated dosing regimens that can cause confusion for the patient and lead to medication errors. Drug absorption is often affected by taking oral chemotherapy medications with or without food, and it is imperative that patients follow proper dosing administration recommendations. These complicated dosing regimens necessitate efforts to improve adherence, not only at the initiation of therapy, but throughout the treatment plan.

The National Comprehensive Cancer Network (NCCN) recommends that specialty pharmacies support increased communication between patients and pharmacists in an effort to improve adherence rates and identify potential safety concerns. Additionally, conveying information gathered from patients to providers is fundamental in preventing fragmented care.

 This recommendation by the NCCN supports the need for the development of proactive medication monitoring systems to reduce adverse drug events and consequential dose adjustments for patients receiving oral chemotherapy.

The Marshfield Clinic health care system includes more than 50 regional sites located throughout northern, western, and central Wisconsin and provides care to more than 380,000 unique patients each year. The health care system has a specialty pharmacy that services patients throughout the entire system. The current practice at Marshfield Clinic Specialty Pharmacy is for the pharmacist to provide an initial consultation to review administration directions and potential adverse events at the start of oral chemotherapy, and then conduct a followup consultation 1 to 2 weeks later to assess for both safety and adherence. The objective of this project was to determine what potential impact a pharmacist could have by providing additional followup appointments to patients receiving oral chemotherapy from a specialty pharmacy.

The project was designed as a prospective, observational, quality improvement pilot project conducted at the Marshfield Clinic Specialty Pharmacy in Marshfield, Wisconsin. Figure 1: Project Flow Chart (online) provides an outline of the project design. The project was deemed exempt from Institutional Review Board review based on its quality improvement status. Medications included in the project were capecitabine, erlotinib, lapatinib, and sorafenib, based on their frequency of use and high incidence of adverse events. Patient inclusion criteria were (1) at least 18 years of age and (2) received a prescription for capecitabine, erlotinib, lapatinib, or sorafenib from Marshfield Clinic Specialty Pharmacy with an anticipated duration of treatment of at least 8 weeks. Patients were excluded if they were unable to participate in 2 additional follow-up appointments. Participants were identified and enrolled by a pharmacist at their standard first follow-up appointment. Verbal consent was documented.

Two follow-up appointments were scheduled for each patient; appointments for capecitabine patients were scheduled on weeks 5 and 8 of the treatment cycle and the remaining medications on weeks 4 and 8. The difference in timing of appointments was due to the cyclic dosing regimen of capecitabine, and appointments were scheduled to be conducted while patients were on therapy instead of during their weeks off between cycles. Visits were conducted telephonically for patient convenience and conducted by the specialty pharmacist or primary investigator. A telephone script was prepared for visits and was individualized to assess for the most common adverse events reported for each specific medication.

The pharmacist assessed the patient’s medication-related needs at each visit and inquired about specific adverse events the patient may have been experiencing. Drug therapy opportunities were identified, categorized, and documented in a Microsoft Access 2003 database in accordance with standard procedure in the specialty pharmacy department. Visits with patients were documented by the pharmacist in the electronic health record (EHR) and cosigned by the prescriber before permanent entry to the EHR. Visits of patients with non—Marshfield Clinic providers were documented outside of the EHR and kept in a secure file.

Descriptive statistics were utilized to evaluate the frequency, type, and severity of each drug therapy opportunity identified. Adverse events were categorized by the NCI Common Toxicity Criteria.

Adherence was documented as missed doses reported by the patient. Results of this project will guide quality improvement efforts addressing opportunities to improve drug therapy in patients receiving treatment with oral chemotherapy, as well as help determine the potential need for expansion of pharmaceutical care services provided by Marshfield Clinic.

A total of 29 patients were enrolled in the project, and 42 follow-up visits were conducted from November 2010 through May 2011. Sixteen patients received capecitabine, 8 patients received erlotinib, 1 patient received lapatinib, 2 patients received sorafenib, and 2 patients were on a combination of 2 of the medications (1 patient taking capecitabine and lapatinib, 1 patient taking capecitabine and erlotinib). All patients approached to take part in the project were willing and able to participate. Baseline characteristics of the participants are shown in Table 1.

The average age of participants was 67 years and 69% were female. Colorectal, breast, and lung cancer were the most common malignancies among participants. Thirty-four percent of patients were receiving intravenous chemotherapy in addition to oral chemotherapy. Eleven patients (38%) were unable to complete the project. Six of these patients (all receiving capecitabine) discontinued therapy due to toxicity; 2 patients were lost to follow-up; 1 patient discontinued therapy due to treatment failure; and 2 patients died during the project period (Table 2).

A total of 5 missed doses were reported by patients from all 42 patient follow-ups. Twenty-six of the 29 patients reported 100% adherence to oral chemotherapy medication. A total of 83 drug therapy opportunities were identified during the 42 follow-up visits; 75 of these were providing patient education and tips for managing adverse events from oral chemotherapy. Figure 2 displays the adverse events for which the pharmacist provided education. The pharmacist identified an average of 2 drug therapy opportunities per patient visit. There was an opportunity to provide patient education for tips on managing adverse events in 34 (81%) of the 42 patient follow-ups conducted.

Fatigue and appetite loss were the most commonly reported adverse events for which a pharmacist was able to provide education and tips for management. Constipation, diarrhea, and skin rash were also common adverse events for which the pharmacist provided patient education. According to the NCI Common Toxicity Criteria, 77% percent of adverse events were categorized as grade 1; 21% were categorized as grade 2; and 1% were grade 3.

 Figure 3: Example of a Specialty Pharmacy (online) provides an example of a specialty pharmacist educational opportunity. Sample drug therapy opportunities other than providing patient education for adverse events are listed in Table 3. The provider was contacted, if necessary, to resolve potential drug therapy concerns.

Impact of Additional Follow-Up Appointments

—Limited studies have examined the role of the pharmacist in the long-term assessment and monitoring of patients receiving oral chemotherapy. The NCCN recognizes the rising role of specialty pharmacy in the care of patients receiving oral chemotherapy and discusses the importance of increased communication between the pharmacy, patient, and provider in the 2010 Task Force Report for Specialty Pharmacy. Greater communication with patients allows for the identification of and assistance in resolving potential drug therapy problems related to adherence, toxicities, and adverse events the patient may be experiencing.

 Of the 42 follow-up visits conducted in our project, as mentioned, there were a total of 83 drug therapy opportunities identified. Ninety percent of these drug therapy opportunities identified were providing additional patient education for adverse events management related to toxicities of oral chemotherapy. Other drug therapy opportunities identified included drug—drug interactions, duplicate therapy, and patient education.

—Patients were very receptive to further contact from their pharmacist, as demonstrated by the 100% participation rate.

—Twenty-one percent of patients in the project were unable to finish both follow-up visits due to discontinuing medication for reasons related to toxicity, demonstrating the importance of proper management of adverse events in the attempt to prevent therapy interruptions.

— Providers were contacted by telephone if drug therapy opportunities were identified that required their immediate attention. Follow-up visits conducted for patients with providers within the Marshfield Clinic system were documented in the EHR and signed by the provider for review before becoming part of the permanent record. Future studies should be done to assess the value of this documentation to the prescribing doctor.

—There were 26 of 29 patients who reported 100% adherence to the prescribed treatment plan. This is superior to the general average adherence rate of about 50% for long-term therapies as reported by the World Health Organization.

 Reported adherence rates to oral antineoplastic agents found in the literature range from 20% to 100%.

A few limitations should be considered when interpreting the results of our pilot project. One limitation was that patients included in the project may have had increased motivation for adherence due to knowing they were involved in a project that was assessing adherence. The patients had additionally already received 2 contacts from a specialty pharmacist before the project follow-up appointments. Another limitation of the project is that 34% of patients were receiving intravenous chemotherapy in addition to oral chemotherapy. These patients often had frequent office visits for intravenous drug administration that provided opportunities for nurses and physicians to offer education for adverse event management.

Patients receiving oral chemotherapy frequently experience adverse events. Due to the high incidence of adverse events and the discontinuation rate, there is a need for continued adverse event management for oral chemotherapy patients. The Marshfield Clinic’s oral chemotherapy patient population is receptive to additional telephonic communication with their pharmacist. Future directions should be geared toward patients solely receiving oral chemotherapy due to their infrequent contact with other health care professionals. As a result of this project, the Marshfield Clinic Specialty Pharmacy has developed an Oral Chemotherapy Patient Management Program, which includes a multidisciplinary approach to providing patient-centric care. This project identifies adverse drug events that are common among patients receiving oral chemotherapy. In the future, it may be valuable to evaluate the impact pharmacists have in decreasing the adverse drug event rate.

1. Weingart SN, Spencer J, Buia S, et al. Medication safety of five oral chemotherapies: a proactive risk assessment. J Oncol Pract. 2011;7(1):2-6.

2. Aisner J. Overview of the changing paradigm in cancer treatment: oral chemotherapy. Am J Health Syst Pharm. 2007;64(9, suppl 5):S4-S7.

3. Liu G, Franssen E, Fitch MI, Warner E. Patient preferences for oral versus intravenous palliative chemotherapy. J Clin Oncol. 1997;15(1):110-115.

4. Hartigan K. Patient education: the cornerstone of successful oral chemotherapy treatment. Clin J Oncol Nurs. 2003;7(6 suppl):21-24.

5. Weingart SN, Flug J, Brouillard D, et al. Oral chemotherapy safety practices at US cancer centres: questionnaire survey. BMJ. 2007;334(7590):407.

6. Lau PM, Stewart K, Dooley M. The ten most common adverse drug reactions (ADRs) in oncology patients: do they matter to you? Support Care Cancer. 2004;12(9):626-633.

7. Schwartz RN, Eng KJ, Frieze DA, et al. NCCN Task Force Report: Specialty Pharmacy. J Natl Compr Canc Netw. 2010;8(suppl 4):S1-S12.

8. Trotti A, Byhardt R, Stetz J, et al Common toxicity criteria: version 2.0: an improved reference for grading the acute effects of cancer treatment: impact on radiotherapy. Int J Radiat Oncol Biol Phys. 2000;47(1):13-47.

9. Burkhart PV, Sabaté E, Adherence to long-term therapies: evidence for action. J Nurs Scholarsh. 2003;35(3):207.

10. Partridge AH, Avorn J, Wang PS, Winer EP. Adherence to therapy with oral antineoplastic agents. J Natl Cancer Inst. 2002;94(9):652-661.

Katherine Backes, PharmD, BCACP, is a clinical pharmacy specialist in clinical pharmacy services at the Marshfield Clinic in Marshfield, Wisconsin.

Sara Griesbach, PharmD, BCPS, BCACP, AEâ€C, is director of clinical pharmacy services and pharmacy residency program director at the Marshfield Clinic in Marshfield, Wisconsin.

Sue Wilhelm, RPh, BCPS, is assistant director of pharmacy operations, pharmacy services at the Marshfield Clinic in Marshfield, Wisconsin, and pharmacy manager of the specialty pharmacy at the Marshfield Clinic.

Gary Plank, PharmD, is corporate director of pharmacy services at the Marshfield Clinic in Marshfield, Wisconsin

Gary Plank, PharmD

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