Seminars in oncology
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Seminars in oncology · Aug 2001
ReviewRole of adjuvant endocrine therapy in early-stage breast cancer.
The value of adjuvant endocrine therapy in saving lives of women with estrogen receptor-positive (ER(+)) early-stage breast cancer cannot be disputed. Tamoxifen has proven to be effective in improving relapse-free and overall survival in both pre- and postmenopausal women with ER(+) early-stage breast cancer. In the meta-analysis of the Early Breast Cancer Trialists' Collaborative Group, the proportional reduction in recurrence and mortality for 5 years of tamoxifen therapy was 50% and 28% respectively for patients with ER(+) tumors. ⋯ In addition, newer, more effective, and less toxic aromatase inhibitors are also being evaluated in clinical trials in the adjuvant setting and have great promise. "Pure" antiestrogens or selective estrogen receptor down-regulators (SERDs) will be studied in adjuvant clinical trials in the near future. Recent data also suggest that molecular markers such as HER-2/neu may predict the response to endocrine therapy, and other predictive factors are currently being evaluated. Lastly, there is renewed interest in neoadjuvant endocrine therapy, a treatment option that may select those patients with early-stage breast cancer most likely to benefit from endocrine therapy.
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Seminars in oncology · Apr 2001
ReviewPaclitaxel-based three-drug combinations for the treatment of small cell lung cancer: a review of the Sarah Cannon Cancer Center experience.
Between June 1993 and September 1999, 217 patients with small cell lung cancer (SCLC) entered three sequential phase II trials evaluating novel paclitaxel-containing three-drug combination chemotherapy regimens. Patients with limited- or extensive-stage SCLC, no previous treatment, and Eastern Cooperative Oncology Group performance status 0 to 2 were eligible. Trials 1 and 2 evaluated the combination of paclitaxel, carboplatin, and etoposide; in the second trial, doses of paclitaxel and carboplatin were higher than in the first trial. ⋯ Paclitaxel-containing three-drug regimens, as evaluated in these three phase II trials, were feasible and highly active in the first-line treatment of SCLC. Randomized trials will be necessary to definitively evaluate the efficacy of these regimens as compared with traditional platinum/etoposide combinations. Semin Oncol 28 (suppl 4):43-47.
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Seminars in oncology · Feb 2001
ReviewDocetaxel (Taxotere) plus trastuzumab (Herceptin) in breast cancer.
The rationale for the combined use of docetaxel (Taxotere; Aventis Pharmaceuticals, Inc, Parsippany, NJ) and trastuzumab (Herceptin; Genentech, South San Francisco, CA) in HER2/neu-overexpressing breast cancer patients are several-fold. Docetaxel is a highly active chemotherapeutic agent in metastatic breast cancer. Response rates, time to progression, and survival are improved when trastuzumab is combined with chemotherapy. ⋯ The preliminary data for the docetaxel and trastuzumab combinations look favorable from both a safety and an efficacy perspective. The lack of cardiac function changes despite frequent cardiac monitoring is promising. For the adjuvant therapy of HER2/neu-overexpressing breast cancer, the high level of efficacy of docetaxel and the need to identify nonanthracycline agents for combined use with trastuzumab place a high emphasis on the potential utility of docetaxel and trastuzumab-based regimens.
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Seminars in oncology · Feb 2001
ReviewCardiac toxicity of trastuzumab (Herceptin): implications for the design of adjuvant trials.
Trastuzumab (Herceptin; Genentech, South San Francisco, CA) is a humanized version of the murine monoclonal antibody 4D5 that was recently approved for the treatment of advanced breast cancer that overexpresses the HER2/neu oncogene. Cardiac toxicity was an unexpected side effect of trastuzumab treatment in the pivotal trials that led to its approval. The incidence of cardiac dysfunction was highly dependent on prior or concurrent doxorubicin exposure. ⋯ For patients treated with trastuzumab concurrently with doxorubicin, the risk of cardiac dysfunction was 29%. The etiology of trastuzumab-associated cardiac dysfunction is unknown, although its dependence on concurrent or prior doxorubicin exposure suggests a common pathophysiologic basis with anthracycline-induced myocardial injury. A number of trials are in progress to evaluate the efficacy and safety of trastuzumab in patients with early stage disease and that will investigate novel strategies to circumvent this serious toxicity.
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Seminars in oncology · Feb 2001
ReviewNew adjuvant strategies for breast cancer: meeting the challenge of integrating chemotherapy and trastuzumab (Herceptin).
Improvements in breast cancer treatment will arrive with better understanding of its biology and through biologically oriented therapeutic interventions as well as better identification of patient populations susceptible to benefit from classical therapies (endocrine and chemotherapy). Among the new chemotherapies, the taxanes have emerged as powerful agents in the treatment of metastatic breast cancer and a strong emphasis has been pursued into their development in the adjuvant setting. Two generations of adjuvant pivotal trials with taxanes have been developed. ⋯ Large-scale clinical research programs are presently being developed and will create a challenge for clinical researchers. The adequate scientific hypothesis, related to the pivotal studies of trastuzumab in the adjuvant setting, require large sample sizes (several thousand patients) and a very strict selection of the patient population (tumors amplifying the HER2 gene). Success in a timely fashion requires global collaboration, dedication to high-standard clinical research, and awareness of all available protocols by oncologists and patients with breast cancer.