Assessment of the Relationship Between Adherence with Antiemetic Drug Therapy and Control of Nausea and Vomiting in Breast Cancer Patients Receiving Anthracycline-Based Chemotherapy

BACKGROUND: There are little prevalence data in the literature on nonadherence to outpatient antiemetic regimens for prophylaxis of chemotherapy-induced nausea and vomiting (CINV). It is unclear whether adherence with outpatient antiemetic regimens is associated with better CINV control. Our previous survey research supports the work of clinical pharmacists in collaborative practice with medical oncologists in improving adherence with antiemetic therapy in women undergoing highly emetic chemotherapy for breast cancer. OBJECTIVES: To (a) evaluate the impact of adherence to delayed antiemetics (days 2-4 following anthracycline-based chemotherapy) on CINV control in breast cancer patients after anthracycline-based chemotherapy and (b) identify patient-related factors associated with nonadherence to delayed antiemetics. METHODS: A single-center, prospective, observational study was conducted from December 2006 to January 2011 in breast cancer patients receiving anthracycline-based chemotherapy (doxorubicin or epirubicin) and antiemetics at the National Cancer Centre Singapore (NCCS), the largest ambulatory cancer center in Singapore. Included patients were aged 21 years or older with confirmed diagnoses of breast cancer and receiving anthracycline-containing chemotherapy with antiemetics. Patients were excluded if they (a) were diagnosed with intestinal obstruction or received concurrent radiotherapy that predisposed them to nausea and vomiting, (b) had vomited in the 24 hours preceding chemotherapy, or (c) had brain metastases that would impair their judgment. Patients documented in a standardized diary their emesis events, severity of nausea, use of rescue therapy with metoclopramide, and compliance with dose instructions for antiemetic drug therapy for 5 days: day 1 was the day of chemotherapy and first day of antiemetic therapy, and day 5 was the day after completion of delayed antiemetic therapy (days 2-4). Three definitions were used to describe the CINV outcomes: (a) complete response (no emetic episodes and no rescue therapy); (b) complete protection (no emetic episodes, no rescue therapy, and no significant nausea [Likert score 2 or less]); and (c) complete control (no emetic episodes, no rescue therapy, and no nausea). The delayed (days 2-5 post-chemotherapy) phase of these endpoints was analyzed. Nonadherence was defined as missing at least 1 dose of the delayed antiemetics from the prescribed regimen. Pearson chi-square or Fisher’s exact tests and multiple logistic regression analysis were used to assess the relationship between adherence and CINV outcomes. RESULTS: Of 519 eligible patients, 88 (17.0%) patients declined participation; 35 (6.7%) were lost to follow-up; and another 35 (6.7%) were excluded due to the absence of therapy with delayed antiemetics according to guideline protocol. Of the 361 (69.6%) patients included in the final analysis, the mean (SD) age was 50.0 (8.9); the majority was Chinese (80.1%) and diagnosed with stage 2 or higher breast cancer (88.1%). A total of 152 patients (42.1%) self-reported nonadherent use of delayed antiemetics. Among all the nonadherent patients (n = 152), 16.4% (n = 25) achieved complete control; 34.2% (n = 52) achieved complete protection; and 58.6% (n = 89) achieved complete response, compared with rates of 26.8% (n = 56), 39.7% (n = 83), and 62.7% (n = 131), respectively, for adherent patients (n = 209). The rate of adherence to dexamethasone, which was prescribed for all study patients, was low (62.6%). After adjusting for potential confounders (ethnicity, educational level, and disease stage), adherent patients were more likely to achieve complete control of CINV (adjusted odds ratio = 1.74, 95% CI = 1.01-3.01, P = 0.048). Among the demographic and CINV risk-factor variables, higher education, alcohol consumption, and prior exposure to other (nonanthracycline-based) chemotherapy regimens were associated with nonadherence (P less than 0.05). CONCLUSIONS: Although 42% of breast cancer patients receiving anthracycline-based chemotherapy were nonadherent with the dose administration protocol for post-chemotherapy antiemetic therapy, there was no significant difference in control of CINV compared with adherent patients except for the category of complete CINV control, defined as no nausea, no emesis, and no use of the rescue medication metoclopramide.