Oncology
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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.
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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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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.