Seminars in oncology
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Seminars in oncology · Feb 2001
North Central Cancer Treatment Group--Mayo Clinic trials in colon cancer.
The adjuvant treatment of colon cancer is now accepted as an effective therapy following surgical resection of the primary tumor in patients at high risk for relapse. Results of studies conducted in the last 10 years have confirmed the benefits of using various 5-fluorouracil (5-FU)-based chemotherapy regimens to decrease recurrence rates and improve patient survival. The North Central Cancer Treatment Group-Mayo Clinic studies have made a significant contribution to establishing the role of adjuvant therapy in colon cancer. ⋯ No differences in efficacy were found in any of the various combinations tested. Current clinical trials are investigating the use of newer agents such as CPT-II in the adjuvant setting. The results of these trials may further improve the efficacy of adjuvant therapy in patients with high-risk colon cancer.
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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) 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
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.