TOP September 2008_v5
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ORAL CHEMOTHERAPY Continued from cover
PHARMACY PRACTICE
development are oral agents. The increasing availability of oral oncology drugs and percentage of oral agents considered “targeted therapies” underscore the importance of maximizing patient adherence with oral chemotherapy regimens, Yee said during a symposium held at the 2008 Hematology Oncology Pharmacy Association/ International Society of Oncology Pharmacy Practitioners joint annual conference. According to Yee, no consensual standard exists for differentiating adherence from nonadherence. Patients who take at least 80% of the prescribed number of pills daily within the correct prescribed period are considered adherent in most standard clinical studies, he explained, although rates as high as 95% have been used to establish adherence in studies of patients with HIV infection and other populations. “Nonadherence to oral chemotherapy can have far-reaching negative consequences,” Yee
Recent FDA
Approvals
• Expanded Approval for Azacitidine Azacitidine (Vidaza; Celgene) has received expanded US Food and Drug Administration (FDA) approval, reflecting new overall survival achieved in the AZA-001 survival study, an international phase 3 trial in patients with higher-risk myelodysplastic syndromes (MDS). In 2004, the demethylation agent became the first therapy approved by the FDA for treatment of MDS; it was approved for all five French American British subtypes of MDS, which include both low-risk and high-risk patients. • New Indication for Bortezomib The FDA has approved bortezomib (Velcade; Millenium, Takeda) for patients with previously untreated multiple myeloma based on the results of an international, open-label, active-control trial. The agent was previously approved as second- or third-line therapy for multiple myeloma and is also approved for patients with mantle cell lymphoma who have received at least one prior therapy.
PHARMACY PRACTICE
• Oral Formulation of Palonosetron An oral formulation of palonosetron hydrochloride (Aloxi; Eisai, Helsinn) has been approved by the FDA for prevention of chemotherapy-induced nausea and vomiting. An injectable form was approved in 2003. • Blood Test for Colorectal Cancer The AMDL-ELISA DR-70(R) (FDP) has been cleared by the FDA for monitoring disease progression in patients previously diagnosed with colorectal cancer. The blood test is the first monitoring product for colorectal cancer cleared by the FDA since 1982.
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G REEN H ILL H EALTHCARE C OMMUNICATIONS
said. Adverse consequences of nonadherence include misinterpretation of a patient’s worsening condition as an absence of drug activity, increased physician visits, unnecessary diagnostic testing, longer length of hospital stay, unnecessary changes in medication dose or regimen, and deterioration of the patient– provider relationship, he noted. Medication adherence can be determined directly through continual observation or the use of blood assays or physiologic markers of drug activity. Indirect methods of determining medication adherence include the use of patient questionnaires, diaries, pill counts, refill rates, electronic monitors, and pharmacy record review. The presence of psychological problems, particularly depression, is a major predictor of medication nonadherence, Yee explained. Other factors associated with nonadherence include cognitive impairment, treatment of asymptomatic disease, adverse medication effects, patient’s lack of belief in treatment benefit, complexity and costs of treatment, and a poor provider–patient relationship (Table 1). Medication adherence can be enhanced through a combination of behavioral, educational, and affective interventions, Yee said (Table 2). Such interventions are designed to influence specific behavioral patterns, convey information, and appeal to emotions and social relations, respectively, in an effort to improve adherence. Yee described the findings of a systematic review of 37 randomized controlled trials of interventions intended to improve medication adherence (JAMA. 2002;288:2868-2879). All trials were in patients with chronic medical conditions and none of the trials enrolled patients with cancer. Of the 37 trials, 12 evaluated educational interventions, 10 evaluated behavioral interventions, and 15 evaluated combined interventions. Educational interventions typically included counseling by a physician, pharmacist, or health educator, and behavioral interventions included dosage simplification, cognitive behavior therapy, and the use of specialized packaging and directly observed therapy. Overall, 20 (54%) of the 37 studies reported a significant increase in at least one adherence measure. The most consistent increases in adher-
Table 1. Major predictors of poor adherence • Presence of psychological problems • Presence of cognitive impairment • Treatment of asymptomatic disease • Inadequate follow-up or discharge planning • Side effects of medications • Patient’s lack of belief in benefit of treatment • Patient’s lack of insight into illness • Poor provider–patient relationship • Missed appointments • Complexity of treatment • Cost of medication, copayment, or both Adapted with permission from Osterberg L, et al. N Engl J Med. 2005;353:487-497.
Table 2. Types of Interventions Behavioral Designed to change adherence by targeting, shaping, or reinforcing specific behavioral patterns Educational (informational or cognitive) Designed to convey information Affective (social/environmental) Designed to change adherence through appeals to feelings and emotions or social relationships and social supports Source: Roter DL, et al. Med Care. 1998;36:1138-1161.
ence were achieved with behavioral interventions that reduced dosing demands and those involving repeated monitoring of medication use with feedback and reinforcement.
Patient adherence programs A review of patient adherence programs implemented at leading sites across the United States was provided by Shauna Choi, PharmD, University of Texas M.D. Anderson Cancer Center, Houston. According to Choi, oral chemotherapy adherence initiatives at her institution include individualized patient counseling, dispensing of one chemotherapy cycle per pill bottle, and the use of patient education materials and industry-sponsored tools written in various languages. A system designed to educate and monitor patients starting new oral chemotherapy has been developed by the Cincinnati Veterans Administration Medical Center. In this system, patients receive education and monitoring from a team member who is assigned particular oral chemotherapy agents and are followed up weekly for adherence and adverse drug reactions (ADRs). The incidence of ADRs in patients receiving oral chemotherapy agents decreased from 33% to 26% during the first few months after implementation of the program, Choi said, and the medication adherence rate during the program has been documented at 94%. At BioScrip, a specialty pharmaceutical healthcare organization, efforts to enhance oral chemotherapy adherence include the reduction of financial barriers to treatment availability. Such efforts involve the identification of economic reality and feasibility before the start of treatment and helping patients navigate cost assistance programs and organizations. A primary adherence enhancement initiative underway at BioScrip is the Refill Adherence Management Program (RAMP). The program is designed to prevent treatment interruptions by addressing ADRs, resolving drug delivery issues, and partnering with physicians to ensure that prescriptions are sent in a timely manner. In patients with HIV infection receiving antiretroviral therapy, RAMP produced an overall adherence rate 20% greater than BioScrip’s customary pharmaceutical services program, Choi said. The implementation of RAMP also led to a 60% increase in the proportion of patients achieving 85% or better adherence levels (96% vs 60%) and a nearly 200% increase in the proportion achieving 95% or better adherence (92% vs 32%). —DSM September/October 2008