A randomized trial of individualized versus standard of care antiemetic therapy for breast cancer patients at high risk for chemotherapy-induced nausea and vomiting.

PURPOSE: Despite triple antiemetic therapy use for breast cancer patients receiving emetogenic chemotherapy, nausea remains a clinical challenge. We evaluated adding olanzapine (5 mg) to triple therapy on nausea control in patients at high personal risk of chemotherapy-induced nausea and vomiting (CINV). METHODS: This multi-centre, placebo-controlled, double-blind trial randomized breast cancer patients scheduled to receive neo/adjuvant chemotherapy with anthracycline-cyclophosphamide or platinum-based chemotherapy to olanzapine (5 mg, days 1-4) or placebo. Primary endpoint was frequency of self-reported significant nausea, repeated for all cycles of chemotherapy. Secondary endpoints included: duration of nausea, overall total control of CINV, Health Related Quality of Life (HRQoL) using FLIE questionnaire, use of rescue mediation and treatment-related adverse events. RESULTS: 218 eligible patients were randomised to placebo (105) or olanzapine (113). From days 0-5 following each cycle of chemotherapy, 41.3% (95%CI: 36.1-46.7%) of patients in the placebo group reported significant nausea compared to 27.7% (95%CI: 23.2-32.4%) in the olanzapine group (p = 0.001). Across all cycles of chemotherapy, patients receiving olanzapine experienced a statistically significant improvement in HRQoL (p < 0.001). Grade 1/2 sedation was the most commonly side effect reported at 40.8% in the placebo group vs. 54.1% with olanzapine (p < 0.001). CONCLUSION: In patients at high personal risk of CINV, the addition of olanzapine 5 mg daily to standard antiemetic therapy significantly improves the control of nausea, HRQoL, with no unexpected toxicities.

Long-term outcomes after adjuvant treatment of sequential versus combination docetaxel with doxorubicin and cyclophosphamide in node-positive breast cancer: BCIRG-005 randomized trial.

BACKGROUND: The optimal regimen for adjuvant breast cancer chemotherapy is undefined. We compared sequential to concurrent combination of doxorubicin and cyclophosphamide with docetaxel chemotherapy in women with node-positive non-metastatic breast cancer. We report the final, 10-year analysis of disease-free survival (DFS), overall survival (OS), and long-term safety. PATIENTS AND METHODS: A total of 3298 women with HER2 nonamplified breast cancer were randomized to doxorubicin and cyclophosphamide every 3 weeks for four cycles followed by docetaxel (AC → T) every 3 weeks for four cycles or docetaxel, doxorubicin, and cyclophosphamide (TAC) every 3 weeks for six cycles. The patients received standard radiotherapy and endocrine therapy and were followed up for 10 years with annual clinical evaluation and mammography. RESULTS: The 10-year DFS rates were 66.5% in the AC → T arm and 66.3% in the TAC arm (P = 0.749). OS was 79.9% in the AC → T arm and 78.9% in the TAC arm (P = 0.506). TAC was associated with higher rates of febrile neutropenia, although G-CSF primary prophylaxis greatly reduced this risk. AC → T was associated with a higher rate of myalgia, hand-foot syndrome, fluid retention, and sensory neuropathy. CONCLUSION: This 10-year analysis of the BCIRG-005 trial confirmed that the efficacy of TAC was not superior to AC → T in women with node-positive early breast cancer. The toxicity profiles differ between arms and were consistent with previous reports. The TAC regimen with G-CSF support provides shorter adjuvant treatment duration with less toxicity. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00312208.

Patient adherence to aromatase inhibitor treatment in the adjuvant setting.

Improvements in adjuvant systemic therapy and detection of early disease have resulted in a decline of breast cancer death rates across all patient age groups in Canada. Non-adherence to adjuvant hormonal therapy in the setting of early breast cancer may significantly affect patient outcome. Factors associated with medication adherence are complex and may be patient-related, therapy-related, and health care provider-related. To date, there is a gap in the literature concerning a comprehensive understanding of factors related to medication adherence with anti-estrogen therapy in the adjuvant setting. The literature suggests that strategies for improving adherence should focus on education of patients, assessment of the ability of patients to understand their disease and related recurrence factors, and facilitation of adherence by patients by providing adequate support and strategies for good self-management. However, more research is needed to better understand how health care providers can support women with breast cancer on oral therapy in the adjuvant setting.

Models of care for early-stage breast cancer in Canada.

There is growing evidence that follow-up for patients with early breast cancer (ebc) can be effectively carried out by the primary health care provider if a plan is in place. Here, we present data from a recent survey conducted in Ontario indicating that a shared-care model could work if communication between all health professionals involved in the care of ebc patients were to be improved. Patients and primary care providers benefit when the specialist provides written information about what their roles are and what to expect. Primary care providers need to have easy access to the specialist to discuss areas of concern. Patients also need to share responsibility for their care, ensuring that they attend follow-up visits on a regular basis and that they discuss areas of concern with their primary health care provider. A shared-care model has the potential to provide the best care for the least cost to the health system.

An updated review on the efficacy of adjuvant endocrine therapies in hormone receptor-positive early breast cancer.

The third-generation aromatase inhibitors (AIS) are largely replacing tamoxifen in the adjuvant treatment of early-stage breast cancer in postmenopausal women with hormone receptor-positive tumours. To date, multiple trials have been conducted comparing tamoxifen treatment with an AI, and all have demonstrated improved disease-free survival with AI treatment. Trials have included direct 5-year comparisons between tamoxifen and an AI, switching to an AI within 5 years after initial tamoxifen treatment, or extending treatment with an AI after 5 years of completed tamoxifen treatment. Some of these trials have been completed; others are ongoing; and head-to-head trial comparisons of individual AIS are also in progress. The present article summarizes the data obtained from various clinical trials of hormonal therapy for early breast cancer. It also reviews recent data so as to shed light on the current status of these therapies. The focus is on the efficacy of treatment with an AI. Toxicity is discussed in the second article in this supplement.

Safety of adjuvant endocrine therapies in hormone receptor-positive early breast cancer.

Postmenopausal patients with hormone-sensitive early breast cancer are typically treated with adjuvant endocrine therapy, which significantly reduces the risk of recurrence. Because treatment is of a long duration, side effects from adjuvant therapy can be problematic. The aromatase inhibitors (AIS) are replacing tamoxifen as first-line treatment agents for early breast cancer. Here, we present the side-effect data associated with AIS in relation to bone, gynecologic, and cardiovascular health and to arthralgia and myalgia. Although AIS have been shown to decrease bone density, increase arthralgia, and affect vaginal health, these adverse events are usually manageable, and several strategies can be followed to improve quality of life in women on AI treatment. To optimize adherence to therapy. It is important that these issues are addressed so that women can benefit from treatment.

Cancer therapy disparity: unequal access to breast cancer therapeutics and drug funding in Canada.

Adjuvant therapy has made a significant contribution in reducing breast cancer-specific mortality. Standard chemotherapeutics and tamoxifen have been the mainstay treatment for years, but recent clinical evidence supports the use of novel small-molecule therapy and aromatase inhibitor therapy in selected settings, challenging not only the traditional paradigm of breast cancer treatment, but also provincial funding of oncologic care across Canada. The disparity in access to aromatase inhibitor therapy for postmenopausal women with early-stage hormone-sensitive breast cancer across Canada is highlighted as an example.