Oncology
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Review Randomized Controlled Trial Comparative Study Clinical Trial
First-line Herceptin monotherapy in metastatic breast cancer.
The pivotal phase II and III Herceptin trials proved the efficacy and safety of second- or third-line single-agent Herceptin and first-line Herceptin in combination with chemotherapy, respectively. In the current trial, 114 patients were randomized to one of two dose groups of first-line Herceptin monotherapy: standard dose of 4 mg/ kg initial dose followed by 2 mg/kg intravenous (i.v.) weekly; or high dose of 8 mg/kg initial dose followed by 4 mg/kg i.v. weekly. The regimen was generally well tolerated. ⋯ When women with stable disease for > or =6 months were included with responders, the clinical benefit rate in IHC 3+ patients was 47%. Median survival was 24.4 months, which is comparable with the survival rate seen in the pivotal phase III combination trial (25 months). Therefore, single-agent Herceptin is an important new option for the first-line treatment of HER2-positive metastatic breast cancer patients.
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Review Comparative Study
Herceptin alone or in combination with chemotherapy in the treatment of HER2-positive metastatic breast cancer: pivotal trials.
Large pivotal phase II and III clinical trials investigated the therapeutic efficacy and safety of the humanized anti-HER2 monoclonal antibody, Herceptin, alone and in combination with standard chemotherapy, respectively, in HER2-positive metastatic breast cancer. Eligible patients were HER2 2+ and 3+ overexpressors, as determined by immunohistochemistry (IHC). Herceptin was well tolerated in both trials. ⋯ Responses in the single-agent Herceptin trial were seen exclusively in FISH-positive patients. Approximately a quarter of HER2 2+ patients test FISH positive and may therefore benefit from therapy. Numerous studies are underway or planned to evaluate other Herceptin combinations and regimens in the metastatic and adjuvant settings.
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Measurement of molecular markers predictive of response to therapy should enable more selective and effective utilization of anticancer agents. The predictive value of HER2 remains a complex and inconclusive subject. In metastatic breast cancer, HER2-positive, ER-positive patients can show responses to endocrine treatment, but experience shorter time to progression and survival than HER2-negative patients. ⋯ HER2 testing has become an integral part of the optimal management of the breast cancer patient. Best current practice in adjuvant breast cancer therapy based on the current knowledge of the potential predictive power of HER2 constitutes not denying tamoxifen to HER2-positive, ER-positive patients or CMF to HER2-positive patients. Outside of clinical trials, adequately dosed anthracycline-based chemotherapy is the current preferred adjuvant treatment option for HER2-positive patients.
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Current therapeutic strategies for primary breast cancer aim to provide improvements in outcome with minimal toxicity to the patient. However, annual relapse rates of up to 12 to 13% during the first 10 years after treatment are seen, and although toxicity has been reduced, it remains a problem in a patient population that is largely asymptomatic. Thus, there is a clear need for more effective therapies. ⋯ Herceptin is effective and well tolerated in the metastatic setting, making it an ideal candidate for use in adjuvant breast cancer therapy. This has led to the design of a number of trials that aim to provide conclusive evidence as rapidly as possible that Herceptin is well tolerated and effective in the adjuvant setting while also addressing the question of which regimen provides greatest benefit. This review describes these trials and explains how differences in practice between North America and Europe have influenced trial design.
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Review Comparative Study
New combinations with Herceptin in metastatic breast cancer.
Preclinical data indicate that trastuzumab (Herceptin) has the potential for synergistic or additive effects in combination with therapies including chemotherapy and hormonal agents, providing the rationale for a number of clinical trials in women with HER2-positive metastatic breast cancer. A recently reported phase II trial has demonstrated that trastuzumab plus vinorelbine is both effective (overall response rate 75%) and well tolerated, with the major side effects being typical of single-agent vinorelbine. ⋯ In addition, trials are investigating whether trastuzumab can reverse the resistance to hormonal therapy that develops in most women with metastatic breast cancer. These and other studies will identify the regimens that produce the best outcomes with the fewest possible side effects in women with HER2-positive breast cancer.