Clinical breast cancer
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Clinical breast cancer · Dec 2008
ReviewIntegrating epothilones into the treatment of patients with metastatic breast cancer: clinical perspectives on incorporating recent data in the practice setting.
The introduction of modern chemotherapy agents, including the taxanes, has improved the prognosis of women with metastatic breast cancer (MBC). Ultimately, however, inevitable intrinsic or acquired resistance to chemotherapy limits treatment options. The epothilones, a novel class of microtubule-stabilizing agents that have incomplete cross-resistance with taxanes and are less susceptible to common mechanisms of resistance, have demonstrated activity in breast cancer. ⋯ Ixabepilone is relatively well tolerated, with the most common side effects being peripheral neuropathy and neutropenia. Other epothilones such as KOS-862, patupilone, ZK-EPO, BMS-310705, and KOS-1584 are being evaluated as therapy for patients with breast cancer, with promising preliminary data. Ongoing research aims to define and optimize the efficacy of the epothilones in an attempt to improve the quality of life and overall survival of individuals with breast cancer.
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Clinical breast cancer · Dec 2008
ReviewActivity of ixabepilone in patients with metastatic breast cancer with primary resistance to taxanes.
Primary drug resistance, defined as disease progression as best response to treatment, presents an important problem in everyday clinical practice. Primary taxane resistance, reported in up to 55% of patients with breast cancer, plays a critical role in minimizing the efficacy of taxane-based chemotherapy for metastatic breast cancer (MBC). The epothilones are a novel class of antineoplastic agents, developed to overcome tumor-resistance mechanisms. ⋯ Ixabepilone demonstrated clinical activity as monotherapy, and in combination with capecitabine, in patients with MBC who had disease progression as best response to previous taxane therapy. Response rates in patients with primary taxane resistance were comparable to responses observed in total patient populations. The clinical results support the hypothesis that ixabepilone can overcome or circumvent primary mechanisms of resistance to taxanes and other chemotherapeutic agents.
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Clinical breast cancer · Oct 2008
Randomized Controlled Trial Multicenter StudyMulticentric, randomized phase III trial of two different adjuvant chemotherapy regimens plus three versus twelve months of trastuzumab in patients with HER2- positive breast cancer (Short-HER Trial; NCT00629278).
Trastuzumab, a monoclonal antibody against the HER2 receptor, is currently approved as a part of adjuvant therapy for patients with HER2-overexpressing breast tumors. The Short-HER study is a phase III randomized, multicentric Italian trial aimed at testing the optimal duration of adjuvant trastuzumab. In this trial, 2500 patients with HER2-positive breast cancer will be randomized to receive the following: (arm A, long) 4 courses of anthracycline- based chemotherapy (doxorubicin/cyclophosphamide or epidoxorubicin/cyclophosphamide) followed by 4 courses of docetaxel or paclitaxel in combination with trastuzumab, followed by 14 additional courses of trastuzumab administered every 3 weeks (for a total of 18 3-weekly doses of trastuzumab); or (arm B, short) 3 courses of 3-weekly docetaxel in combination with weekly trastuzumab (for a total of 9 weekly doses of trastuzumab) followed by 3 courses of 5-fluorouracil/epirubicin/cyclophosphamide. The primary objective is disease-free survival.
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Clinical breast cancer · Oct 2008
Multicenter StudyRetrospective evaluation of clinical outcomes in patients with HER2-positive advanced breast cancer progressing on trastuzumab-based therapy in the pre-lapatinib era.
Patients with HER2-positive breast cancer whose disease has become resistant to the anti-HER2 monoclonal antibody trastuzumab can benefit from lapatinib, a dual epidermal growth factor receptor/HER2 tyrosine kinase (TK) inhibitor. Before the availability of this compound, trastuzumab was often continued beyond disease progression, usually in addition to further chemotherapy, an approach which was not based on randomized studies. We sought to retrospectively compare the clinical outcomes of patients who, upon progression during an initial trastuzumab-based regimen, stopped or continued trastuzumab in addition to further chemotherapy. ⋯ Patients with HER2-positive advanced breast cancer developing tumor progression during an initial trastuzumab-based regimen did not seem to benefit significantly from the continuation of trastuzumab in addition to chemotherapy. For these patients, there is evidence from a large randomized trial that effective HER2 targeting can be accomplished by inhibiting the HER2 TK activity with lapatinib.