The emerging role of Lapatinib in HER2-positive breast cancer
ABSTRACT In breast cancer, overexpression of HER2 is associated with an aggressive tumor phenotype and poor prognosis. Lapatinib has demonstrated benefit in combination with capecitabine in patients with HER2-positive locally advanced and metastatic breast cancer that has progressed after prior treatment with an anthracycline, a taxane, and trastuzumab. It has also demonstrated benefit with paclitaxel in patients with metastatic disease not previously treated with chemotherapy. This review discusses results from clinical trials suggesting an advantage with the use of lapatinib with other treatment modalities in the setting of metastatic and locally advanced disease.
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ABSTRACT: The Her2/neu status is of great clinical value in breast tumor patients. Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) techniques are the test of choice for many practicing pathologies. The main objective of this retrospective study was to investigate the relationship between Her2/neu breast cancer amplification and overexpression (DNA, mRNA and protein). To accomplish this goal, we evaluated Her2/neu mRNA expression by real-time quantitative RT-PCR, gene amplification by FISH and protein expression by IHC. An excellent correlation between FISH and IHC Her2/neu results was observed, confirming that protein levels were directly related to DNA amplification. Polysomy 17 was frequently found in tumors showing Her2/neu overexpression. However, we did not find any statistically significant correlation among DNA, mRNA and protein levels, suggesting that Her2/neu could be post-transcriptionally regulated. There was a highagreement between Her2/neu gene amplification and protein overexpression but not mRNA expression levels. Nevertheless, IHC3+ and FISH-positive tumors indicated higher expression levels of Her2/neu mRNA by RT-PCR than those observed in IHC and FISH-negative tumors. These findings question the relevance of quantitative RT-PCR in routine assessment of Her2/neu overexpression in human breast cancer in the clinical laboratory setting.Pathobiology 01/2010; 77(1):38-45. DOI:10.1159/000272953 · 2.32 Impact Factor
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ABSTRACT: The treatment of recurrent transitional cell carcinoma (TCC) remains an unmet clinical need. This study assessed lapatinib, a dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) and HER-2, as second-line therapy in patients with locally advanced or metastatic TCC. This was a single-arm, multicenter, open-label, prospective phase 2 study. Patients with TCC whose disease progressed on prior platinum-based chemotherapy received lapatinib until disease progression or unacceptable toxicity, with evaluations for response by Response Evaluation Criteria In Solid Tumors criteria performed every 8 weeks. The primary endpoint of the current study was objective tumor response rate. Secondary endpoints included safety, time to disease progression, and overall survival. Fifty-nine patients were enrolled in the study, 25 of whom (42%) could not be evaluated for response. The primary endpoint of an objective response rate (ORR) >10% was observed in 1.7% (95% confidence interval [95% CI], 0.0%-9.1%) of patients; however, 18 (31%; 95% CI, 19%-44%) patients achieved stable disease (SD). The median time to disease progression and overall survival (OS) were 8.6 weeks (95% CI, 8.0 weeks-11.3 weeks) and 17.9 weeks (95% CI, 13.1 weeks-30.3 weeks), respectively. Clinical benefit (ORR and SD) was found to be correlated with EGFR overexpression (P = .029), and, to some extent, HER-2 overexpression. The median OS was significantly prolonged in patients with tumors that overexpressed EGFR and/or HER-2 (P = .0001). Lapatinib was well tolerated. The study was considered to be negative because it did not meet its primary endpoint; however, further analysis demonstrated an improvement in OS in a subset of patients with tumors overexpressing EGFR and/or HER-2, which is encouraging and warrants further investigation.Cancer 07/2009; 115(13):2881-90. DOI:10.1002/cncr.24337 · 4.90 Impact Factor
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ABSTRACT: Issues surrounding the prevention and management of severe oral mucositis in patients with head and neck cancer and patients receiving targeted anticancer therapies are reviewed. Cancer therapy-related mucositis is associated with many negative and potentially life-threatening sequelae. Patients receiving chemoradiotherapy for head and neck cancer are at high risk for severe oral mucositis, but there are currently no definitive recommendations on pharmacologic preventive strategies. Recently published evidence on the use of palifermin to combat oral mucositis during chemoradiotherapy for head and neck cancer is encouraging, with two randomized controlled trials indicating an absolute risk reduction of about 15%; however, palifermin use was not associated with lower rates of mucositis-related treatment delays or chemotherapy dosage reductions, and concerns about optimal dosage and cost-benefit issues persist. Oral mucositis due to targeted therapies for renal cell carcinoma and other disorders (e.g., kinase inhibitors, mammalian target of rapamycin inhibitors) is generally less severe than mucositis caused by conventional cytotoxic chemotherapy. For both types of mucositis, recommended management strategies include good oral hygiene and optimal pain control. Research in this area continues to be complicated by investigators' use of varying terminology and mucositis classification schemes. Palifermin appears to reduce the frequency of oral mucositis in patients treated for head and neck cancer, but its place in therapy has not been determined. Although the oral complications of targeted therapies are clinically distinct from those of conventional cytotoxic therapy, the literature recommends similar palliative management strategies for both.American journal of health-system pharmacy: AJHP: official journal of the American Society of Health-System Pharmacists 06/2012; 69(12):1031-7. DOI:10.2146/ajhp100531 · 2.21 Impact Factor