Several oral chemotherapies and biologic therapies have been introduced in the past decade for use alone and combined with intravenous chemotherapy. The role of oral chemotherapy agents in cancer management will likely increase.1 Oral chemotherapy dosing regimens have been able to “reframe some cancers as chronic diseases requiring chronic therapy.”2 However, oral agents that are used for liver and renal cancer (i.e., sorafenib),3 gastrointestinal stromal tumors (GIST; i.e., sunitinib),4 and non–small cell lung (NSCLC) or pancreatic cancers (i.e., erlotinib)5 are reported to have the potential for toxicity,6 and may pose a significant adherence risk, particularly in the first 30 days of therapy.7 Dose modifications and outright discontinuation of therapy are common responses to these toxicities.
The degree to which a patient follows a treatment regimen as assigned by the health care provider has been described in a variety of ways. The term adherence has been recognized as a major health outcome in today’s health care system, and reflects “the extent to which the patient takes medications as prescribed.”8 Nonadherence is defined as any deviation from physician instructions for the prescribed medications, and exerts a tremendous burden on the health care system in terms of higher costs and poorer health outcomes. Adherence rates for most chronic conditions that use long-term therapies have been shown to be 40% to 50%. Nonadherence can occur in various forms, such as patient failure to initiate therapy, unclaimed prescriptions, filling the prescription but not consuming the medication as scheduled, or premature discontinuation of medication because of side effects.8 Monitoring of adherence is crucial for health care providers, including physicians, because it helps them determine treatment effectiveness, toxicity, and safety. Adherence can be assessed using a variety of direct and indirect methods.
Oral chemotherapy is subject to several factors that can impact adherence, and hence total health care costs, including 1) patient self-administration and medication monitoring; 2) patients’ inability to read, understand, or follow complex instructions for self-administration9; 3) compliance risk, which may reflect inadequate adherence, overadherence, or reduced persistency10; 4) inadequate identification and reporting of, and response to, adverse events; 5) drug interactions with food and other medications; and 6) apparent nonresponsiveness to a drug regimen, which may also result in chemotherapy resistance. Apart from these reasons, the complexity of oral chemotherapy regimens adds further challenges to adherence because patients do not always understand the impact of missed doses and may misunderstand directions, which could lead to either underdosing or overdosing.
Limited research is published on adherence to oral anticancer regimens and its relationship to patient outcomes. A study by McCowan et al.11 found that only 50% of women in a cohort completed the 5-year course of tamoxifen treatment. A recent survey of managed care organizations showed that approximately 45% of oral chemotherapy is dispensed through retail pharmacy channels, 31% through specialty pharmacies, 16% through mail order, and only 7% through a physician’s office.12 Because oral chemotherapeutic agents are often covered under the pharmacy benefit plans for individuals who have insurance coverage, they are commonly dispensed through pharmacy channels. Their significant potential toxicity, adherence concerns, high patient self-management requirements, and high costs together suggest the need for targeted pharmacy care management programs to monitor and facilitate appropriate medication use.
Walgreens Oral Chemotherapy Cycle Management Program (CMP) is an evidence-based clinical program that provides clinical management and support to patients who receive sorafenib, sunitinib, or erlotinib for the treatment of liver or kidney cancers; GIST; or NSCLC and pancreatic cancers, respectively.13 The CMP team consists of oncology nurses and pharmacists, and provides clinical management through education, monitoring, and counseling of patients via telephone at predetermined intervals. Patients are contacted on day 10 and 20 during the first month of therapy, and monthly thereafter to ensure that they have initiated the prescribed therapy, that any side effects are recorded and graded, and that appropriate management steps are taken. Additionally, an oncology trained pharmacist or nurse conducts a midcycle assessment to determine whether the patient is tolerating the therapy. The midcycle assessments are drug-specific and assess for drug-specific side effects, which are graded according to the National Cancer Institute toxicity criteria.14 A drug-specific oncology clinical algorithm crafted and standardized by Walgreens Oncology Advisory Board is used to guide the CMP team to not only ask the patients appropriate questions regarding their therapy and any side effects they may be experiencing, but also identify areas in which appropriate teaching can be provided. Patient education is provided according to the FDA-approved patient information sheets.
If grade 2 or 3 adverse events are noted, the prescribing physician is contacted and a report is faxed, detailing the findings of Walgreens’ clinicians along with the dates the patient started/stopped therapy, adherence issues, and side effects. The report requests that the prescribing physician consider this new information and then contact Walgreens regarding any revisions to the oral chemotherapy regimen or use of supportive care drugs that have been indicated. Patients are also provided with a toll-free number at which they can reach a pharmacist 24/7 to discuss any questions regarding their chemotherapy or any side effect issues they may be experiencing.
In an effort to minimize drug waste that may result from therapy modifications, participating plan sponsors may instruct Walgreens Specialty Pharmacy to initially dispense a partial supply of the patient’s first month’s medication (i.e., “split-fill”), followed by the balance of the month’s supply if the patient tolerates the medication and does not experience any serious (i.e., grade 2 or 3) adverse events. If serious adverse events, intolerability, therapy ineffectiveness, or patient death are identified at midcycle assessment, the remainder of the month’s supply is not dispensed.
The overall objective of the CMP is to address factors that contribute to nonadherence, improve quality and satisfaction of both the patient and provider, and impact cost and wastage. This is achieved through 1) increasing patient understanding and awareness of the treatment regimen and importance of adherence; 2) identifying side effects and complications from medications, which, with appropriate intervention, can reduce complications and adverse events; 3) communicating regularly with patients and health care providers and informing them about wastage prevention from midcycle changes in dosage and discontinuation of therapy; and 4) allowing monthly medications to be shipped as a split-fill, thereby enabling health plans to control potential wastage.
VanelliMPedanALiuN. The role of patient inexperience in medication discontinuation: a retrospective analysis of medication non persistence in seven chronic illnesses. Clin Ther2009;31:2628–2652.
Cancer Therapy Evaluation Program. CTEP NCI Guidelines: Adverse Event Reporting Requirements. Effective January12005. National Cancer Institute Web site. Available at: http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/newadverse_2006.pdf. Accessed March 13 2012.
WolfMSDavisTCShrankW. To err is human: patient misinterpretations of prescription drug label instructions. Patient Educ Couns2007;67:293–300.
McCowanCShearerJDonnanPT. Cohort study examining tamoxifen adherence and its relationship to mortality in women with breast cancer. Br J Cancer2008;99:1763–1768.
BlansettL. Changing reimbursement policies and trends presentation to association of community cancer centers. 2009. Available at: www.amcp.org/WorkArea/DownloadAsset.aspx?id=11843. Accessed March 20 2012.
Outlook: state of the industry report 2009. Walgreens Specialty Pharmacy. Available at: http://www.walgreenshealth.com/pdf/newsletterreport/SOIReport2009.pdf. Accessed March 13 2012.
Cancer Therapy Evaluation Program. Common Toxicity Criteria Manual. Version 2.0. June11999. National Cancer Institute Web site. Available at: http://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcmanual_v4_10-4-99.pdf. Assessed May 20 2011.
EisenTOudardSGravisG. Sorafenib for older patients with renal cell carcinoma: subset analysis from a randomized trial. J Natl Cancer Inst2008;100:1454–1463.
HassettMJO’MalleyAJPakesJR. Frequency and cost of chemotherapy-related serious adverse effects in a population sample of women with breast cancer. J Natl Cancer Inst2006;98:1108–1117.