Seminars in oncology
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Seminars in oncology · Jun 1999
ReviewThe role of docetaxel (Taxotere) in neoadjuvant chemotherapy of breast cancer.
Neoadjuvant chemotherapy has become standard therapy in the management of breast cancer patients with locally advanced disease with inoperable tumors and inflammatory breast cancer. Patients with earlier stage breast cancer and operable tumors may also benefit from treatment with neoadjuvant chemotherapy. Docetaxel (Taxotere; Rhône-Poulenc Rorer, Collegeville, PA) is thought to be one of the most potent agents in the treatment of metastatic breast cancer and is therefore being investigated for its likely benefit in preoperative, neoadjuvant regimens. ⋯ Preliminary findings demonstrate high complete and partial response rates and a tolerable toxicity profile. These results are consistent with the view that incorporation of docetaxel in neoadjuvant chemotherapy regimens will contribute to improved patient outcome. Ongoing studies will provide important information regarding the most appropriate regimens and schedules of docetaxel to use in the preoperative, neoadjuvant setting.
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Seminars in oncology · Jun 1999
ReviewNew approaches in the adjuvant and neoadjuvant therapy of non-small cell lung cancer, including docetaxel (Taxotere) combinations.
Among the issues debated in the therapy of early non-small cell lung cancer are whether postoperative chemotherapy improves survival, whether postoperative radiation therapy has some benefit either in local control or in the prevention of distant recurrence, and whether neoadjuvant treatment benefits patients with stage IIIA disease. The role of surgery is being investigated in the North American Intergroup Trial, in which concurrent chemoradiotherapy followed by surgery and postoperative chemotherapy is compared with concurrent chemoradiotherapy alone. ⋯ However, even in these patients, the detection of tumor DNA in serum is a clear indication for postoperative chemotherapy. A trial undertaken by the Spanish Lung Cancer Group is currently investigating a novel neoadjuvant regimen involving gemcitabine, cisplatin, and weekly docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) in patients with mediastinoscopically confirmed N2 disease.
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Seminars in oncology · Jun 1999
Clinical TrialDocetaxel (Taxotere) in combination with vinorelbine in non-small cell lung cancer.
Following encouraging preclinical evidence suggesting anticancer synergy when docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) and vinorelbine are administered together, a clinical trial was designed to determine the maximum tolerated dose of the combination when given with granulocyte colony-stimulating factor support to 27 patients with advanced non-small cell lung cancer. Doses were escalated in stages to a maximum of 45 mg/m2 vinorelbine and 60 mg/m2 docetaxel, both administered on day 1 of a 2-week cycle. Hematologic toxicity was mild, with febrile neutropenia complicating only four of the 209 cycles delivered. ⋯ Major response was seen in 37% of patients. The median survival was 9 months and 1-year survival was approximately 35%. The combination of 45 mg/m2 vinorelbine and 60 mg/m2 docetaxel has now moved into a phase II trial.
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Seminars in oncology · Jun 1999
Clinical TrialDocetaxel (Taxotere) administered in weekly schedules.
The administration of a weekly low-dose taxane markedly reduces the severity of myelosuppression compared with a once-every-3-week schedule and allows the dose intensity (mg/m2/wk) of treatment to be increased. The dose-limiting toxicity observed in a weekly phase I trial was fatigue/asthenia. The maximum tolerated dose of a weekly docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) phase I study was 43 mg/m2; 36 mg/m2 was recommended for further study. ⋯ Other studies have been conducted to evaluate the efficacy and safety of the weekly schedule. One such study is an ongoing phase II trial in elderly or medically unfit patients with previously untreated advanced non-small cell lung cancer in whom weekly docetaxel appears active and well tolerated. Further investigation of weekly docetaxel alone or in combination is warranted.
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Seminars in oncology · Jun 1999
ReviewRecent progress in the clinical development of docetaxel (Taxotere).
As a result of their substantial antitumor activity, clinical development of the taxanes has moved rapidly from second-line treatment of anthracycline-refractory metastatic breast cancer to current evaluation in large, adjuvant trials. New information suggests that the mechanism of action of taxanes may include cell death by induction of apoptosis and by antiangiogenic properties. In vitro analyses demonstrate docetaxel (Taxotere; Rhône-Poulenc Rorer, Collegeville, PA) to be 100-fold more potent than paclitaxel in bcl-2 phosphorylation and apoptotic cell death. ⋯ The docetaxel plus trastuzumab combination demonstrates synergy in vitro, in contrast to additivity demonstrated with paclitaxel plus trastuzumab. Several trials of the docetaxel (every 3 week and weekly) plus trastuzumab combination are ongoing for which the preclinical observations of synergy are hoped to translate into greater clinical activity and improved survival. The development of additional docetaxel combinations, schedules, and regimens as a result of the newly available therapies in the management of breast cancer holds promise for the future.