ABSTRACT
Human epidermal growth factor receptor-2 (HER2)-positive breast cancer is an aggressive form of breast cancer associated with poorer prognosis and shortened survival. Primary and acquired resistance to existing HER2-targeted therapies presents a challenge for the management of patients with HER2-positive metastatic breast cancer. Ado-trastuzumab emtansine, a drug-antibody conjugate, has shown promising results for patients failing prior treatment with trastuzumab. Ado-trastuzumab emtansine consists of the monoclonal antibody trastuzumab linked to a potent microtubule inhibitor (emtansine), allowing a targeted delivery of chemotherapy to cells that overexpress HER2. Ado-trastuzumab emtansine has been approved for use in patients with metastatic breast cancer who have failed prior therapy with trastuzumab and a taxane. Although well-tolerated in clinical trials, thrombocytopenia has been reported and platelet values should be monitored closely. Increased liver enzymes and bilirubin, as well as cardiotoxicity, have also been documented, and recommendations for dose reduction or discontinuation due to these toxicities are available. Clinical trials are currently ongoing to further define the role of ado-trastuzumab emtansine in both the metastatic and early breast cancer settings.
Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Immunoconjugates/therapeutic use , Maytansine/analogs & derivatives , Receptor, ErbB-2/antagonists & inhibitors , Tubulin Modulators/therapeutic use , Ado-Trastuzumab Emtansine , Animals , Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Agents/adverse effects , Breast Neoplasms/enzymology , Breast Neoplasms/pathology , Female , Humans , Immunoconjugates/adverse effects , Maytansine/adverse effects , Maytansine/therapeutic use , Neoplasm Metastasis , Receptor, ErbB-2/metabolism , Signal Transduction/drug effects , Trastuzumab , Treatment Outcome , Tubulin Modulators/adverse effectsABSTRACT
BACKGROUND: Trastuzumab has become a mainstay of therapy for human epidermal growth factor receptor-2 overexpressed breast cancer in nearly all stages of the disease. Like many monoclonal antibodies, trastuzumab is associated with infusion-related reactions (IRRs) that are not well described, and incidence varies widely between reports (0.7%-40% of patients). MATERIALS AND METHODS: A retrospective chart review of breast cancer patients who received trastuzumab was conducted. The primary objective was to describe the incidence, risk factors, and management of IRRs during the first 12 weeks of trastuzumab therapy in a general population of breast cancer patients. RESULTS: A total of 197 patients who received trastuzumab (1,788 doses) were evaluated. Thirty-three IRRs were identified in 32 patients, resulting in an incidence of 16.2% of patients and 1.8% of doses. All IRRs were mild or moderate in severity and were successfully managed with supportive medications and/or by temporarily stopping the infusion. All patients received subsequent cycles of trastuzumab, with only one patient experiencing a subsequent reaction. Body mass index, stage of disease, and use of premedications were significantly associated with IRRs by multivariate logistic regression analysis. CONCLUSION: Overall, these results support that the vast majority of IRRs occur with the first infusion, are mild in severity, and are easily managed. In addition, risk factors were identified that may help to identify a population of patients at increased risk of IRRs who may benefit from premedication.
Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Breast Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Female , Humans , Incidence , Infusions, Intravenous , Middle Aged , Retrospective Studies , Risk Factors , TrastuzumabABSTRACT
PURPOSE: Report descriptive outcome measures related to the quality of pharmacist-managed anticoagulation care with warfarin in patients with breast cancer since the formation of the anticoagulation management service (AMS). METHODS: Retrospective review of 145 patients with breast cancer (median age 54 years) receiving warfarin therapy for venous thromboembolism (VTE) managed by the pharmacist-run AMS between 1998 and 2005. RESULTS: The median time followed by the AMS was 151 days. Fifty three percent (n = 1651) of total lab draws (n = 3129) were within the target therapeutic INR range 2-3. Recurrent thrombosis occurred in 4.1% of patients. Minor bleeding occurred in 18.6% of patients and major bleeding occurred in three patients (2.1%, gastrointestinal, intra-abdominal, and subdural hematoma). CONCLUSION: To date, this is the largest known published database of cancer patients receiving anticoagulation in a pharmacist-managed anticoagulation service. Recurrent VTE rates, major and minor bleeding rates, and percentage of time spent within the therapeutic range are slightly different in our patient population compared to an oncology population receiving warfarin and a non-oncology population with warfarin managed by AMS. Oral anticoagulation with warfarin is an effective, albeit complicated, treatment for venous thromboembolism in the oncology population. Although low-molecular weight heparin (LMWH) therapy is now the preferred treatment for thrombosis in malignancy, warfarin is still relevant in patients who are unable to receive treatment with LMWH. This report provides valuable information supporting coordinated anticoagulation therapy with a pharmacist-managed service in a breast cancer-specific population, and contributes to the growing data supporting the challenging nature of maintaining warfarin anticoagulation in patients with cancer.
