Seminars in oncology
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Seminars in oncology · Oct 1998
Clinical TrialTaxoids in combination with epirubicin: the search for improved outcomes in breast cancer.
The combination of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and either doxorubicin or epirubicin has significant activity against metastatic breast cancer. However, the optimal schedule in terms of activity and toxicity is still under investigation. The use of docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) in combination with anthracyclines is also active and could represent a safe and favorable alternative. ⋯ Severe fluid retention and symptomatic cardiotoxicity were not seen. Responses occurred at doses of 75 mg/m2 docetaxel plus 90 mg/m2 epirubicin and above. However, the proportion of responders did not increase with increasing dose, and the 75 mg/m2 docetaxel/90 mg/m2 epirubicin combination has been selected for further phase II study.
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The recommended weekly dose and the maximum tolerated weekly dose of docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) have yet to be determined. We report that a weekly dose of up to 40 mg/m2 docetaxel for 6 weeks is active in pretreated patients with metastatic breast cancer. From a preliminary study, this dose-dense schedule appears to induce less hematologic toxicity than a schedule of 100 mg/m2 every 3 weeks while achieving similar response rates and may represent a valuable alternative involving a shorter treatment time in the palliative therapy of advanced disease in higher-risk patients. The dose-dense weekly administration of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) also appears to be active, although the toxicity profiles of the two taxanes may differ.
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Seminars in oncology · Oct 1998
ReviewEfficacy and toxicity of irinotecan in patients with colorectal cancer.
In six published phase II trials, irinotecan (CPT-II; Camptosar; Pharmacia & Upjohn Co, Kalamazoo, MI) has demonstrated consistent activity with response rates of approximately 13% to 27% in patients with advanced colorectal cancer (CRC) refractory to 5-fluorouracil (5-FU) therapy. Similar response and median survival rates have been achieved using either the US regimen (once a week for 4 weeks followed by a 2-week rest) or the European regimen (once-every-3-week schedule). The optimal administration schedule for irinotecan is uncertain. ⋯ Irinotecan has been explored as a single agent in patients with newly diagnosed CRC and has generated response rates in the range of 19% to 32% and a median survival time of approximately 12 months, suggesting a level of antitumor activity similar to that observed with 5-FU and leucovorin. Two recently completed phase III studies in 5-FU-refractory patients have shown that treatment with irinotecan confers a survival advantage compared with treatment with infusional 5-FU or best supportive care. Current studies focus on the activity of irinotecan as part of combined chemotherapy in patients with newly diagnosed advanced-stage CRC, as part of combined-modality therapy with radiation therapy, and as adjuvant chemotherapy for patients with locally advanced CRC.
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There has been a gradual evolution in the philosophy of treatment for metastatic breast cancer. It has long been known that endocrine therapy, radiotherapy, and chemotherapy could offer substantial palliative benefits to patients with symptomatic metastases. While these quality of life issues remain crucially important, it is increasingly recognized that the survival of patients with this condition also appears to be improving as a result of therapeutic advances. ⋯ The results of phase II studies suggest that of these agents, used at the recommended doses, docetaxel (Taxotere, Rhône-Poulenc Rorer, Antony, France) may be the most active, achieving an objective response rate of 59% in minimally pretreated patients and 47% when used in second-line treatment. In these studies, docetaxel was given at the standard dose of 100 mg/m2 over 1 hour. Recent results from phase III studies in which individual studies with docetaxel and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) have been compared with standard therapies indicate that docetaxel is the most active single agent in metastatic breast cancer.