Seminars in oncology
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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
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.
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Seminars in oncology · Feb 2001
ReviewDocetaxel (Taxotere) in combination with radiation therapy and the potential of weekly administration in elderly and/or poor performance status patients with advanced non-small cell lung cancer.
A randomized phase II trial conducted by the Cancer and Leukemia Group B in patients with unresectable non-small cell lung cancer showed that induction chemotherapy followed by concurrent radiotherapy and chemotherapy was feasible when cisplatin was administered together with either gemcitabine, vinorelbine, or paclitaxel. The dominant toxicity was esophagitis. Preliminary survival data are encouraging. ⋯ In this unfavorable group, weekly docetaxel produced a 19% objective response rate and with further follow-up, 1-year survival is 28%. This level of activity is similar to other single agents recently evaluated in more favorable patient groups. The lack of myelosuppression seen with weekly administration suggests that the dose intensity of docetaxel could be maintained in combination regimens.
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Seminars in oncology · Feb 2001
ReviewRationale for trastuzumab (Herceptin) in adjuvant breast cancer trials.
The discovery of the HER2/neu proto-oncogene and its role in the pathogenesis of breast cancer tumors, and the development of the anti-HER2 monoclonal antibody, trastuzumab (Herceptin; Genentech, South San Francisco, CA), directed against the HER2 receptor represent major milestones in the research developments in breast cancer, making trastuzumab the first monoclonal antibody available for treatment of this disease. Clinical trials in HER2-positive patients have demonstrated that the combined use of targeted therapy with trastuzumab in conjunction with cytotoxic chemotherapy is associated with improved time to disease progression and overall survival. Unfortunately, findings also demonstrate an increased risk for cardiotoxicity when trastuzumab is combined with anthracyclines. ⋯ The adjuvant trial design for the Breast Cancer International Research Group uses a control arm of doxorubicin/cyclophosphamide for four cycles followed by docetaxel for four cycles and the second arm contains the addition of trastuzumab to the taxane sequence. The third arm, a non-anthracycline-containing regimen, contains docetaxel, a platinum agent (either cisplatin or carboplatin), and trastuzumab. The rationale for the selection of this three-drug regimen is based on the biology of the system and preclinical and clinical findings that demonstrate a high potential for clinical synergy.