Oncology
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The taxanes and Herceptin have been shown to possess significant clinical activity in metastatic breast cancer. Preclinical testing of taxane/Herceptin combinations demonstrated additive and synergistic interactions with paclitaxel and docetaxel, respectively. In a pivotal clinical trial, combination of paclitaxel (3-weekly) and Herceptin was associated with an increased response rate compared with paclitaxel monotherapy (41% vs. 17%; p = 0.001). ⋯ The preliminary results of a trial of weekly docetaxel and Herceptin demonstrate a response rate of 54% in 13 evaluable patients. Additional European trials of Hercep- tin/taxane combinations as first- and second-line and adjuvant therapy are ongoing. The results of the studies to date indicate that regimens combining Herceptin with 3-weekly and weekly taxane are effective and well tolerated.
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HER2 amplification/overexpression is a marker of poor prognosis in breast cancer. The prognostic impact of HER2 positivity is lower in node-negative compared with node-positive women. The only significant, independent prognostic factors in breast cancer are node status, HER2 status and menopausal status. ⋯ The second theory fits well with two breast cancer subsets and the characteristics of ADH and DCIS. The first type of IDC occurs in older patients, progresses slowly due to estrogen dependency but is aggressive long term. The other type progresses rapidly, is HER2 positive and is more likely to occur in young patients.
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Human epidermal growth factor receptor-2 (HER2/erbB-2) belongs to a family of four transmembrane receptors involved in signal transduction pathways that regulate cell growth and differentiation. Overexpression/amplification of HER2 is associated with malignancy and a poor prognosis in breast cancer. HER2 acts as a networking receptor that mediates signaling to cancer cells, causing them to proliferate. ⋯ Removal of HER2 from the cell surface or inhibition of its intrinsic enzymatic activity may reduce oncogenicity. Our research suggests that the antitumor efficacy of HER2-specific antibodies such as Herceptin relates to their ability to direct HER2 to a Cbl- dependent endocytosis and degradation pathway. The reported clinical therapeutic efficacy of anti-HER2 monoclonal antibodies in breast cancer highlights the importance of understanding the biology of HER2.
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Hodgkin's disease remains one of the few malignant diseases which can be cured by modern chemotherapy in most cases even in advanced stages. Adriamycin-containing chemotherapy regimens are considered as the standard therapy which induce long-term remission in about 60-70% of patients. The ABVD scheme, developed by Bonadonna and colleagues in Milan, has a favorable toxicity profile and causes less myelotoxicity, acute leukemia or sterility relative to many previous treatment programs containing alkylating agents. ⋯ These new drug combinations are currently analyzed and compared with ABVD in several international trials. While the addition of radiotherapy improved disease control in some trials a survival benefit was not identified and the role of radiotherapy remains controversial. High dose programs remain experimental in advanced stage Hodgkin's disease and should be restricted to prospective clinical trials.
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Review
New advances in lung cancer chemotherapy: topotecan and the role of topoisomerase I inhibitors.
Objective tumor responses and survival rates with standard chemotherapy options for small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) have been disappointing. However, several promising new classes of agents have emerged in recent years, including the taxanes, mitotic spindle inhibitors, antimetabolites, and topoisomerase I and II inhibitors. The molecular target of several of these new agents is topoisomerase I, an enzyme that is essential for DNA replication and is up-regulated in tumor cells. ⋯ Preliminary trials also indicate that topotecan is well tolerated and has activity in the first-line treatment of NSCLC. In this article an overview of new agents in lung cancer chemotherapy is provided, with particular attention paid to the topoisomerase I inhibitors. A review of topotecan--the first topoisomerase I inhibitor to be approved for second-line therapy in SCLC--is presented as an illustration of the promise these new agents hold for the treatment of SCLC and NSCLC.