Seminars in oncology
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Seminars in oncology · Jun 1999
Review Randomized Controlled Trial Clinical TrialDocetaxel (Taxotere) plus doxorubicin-based combinations: the evidence of activity in breast cancer.
The high individual response rates of doxorubicin and docetaxel (Taxotere; Rhône-Poulenc Rorer, Collegeville, PA) as single agents in breast cancer and their lack of cross-resistance provide the rationale for investigation of the combination of these two uniquely acting agents. A dose-finding study defined the recommended doses for the combination given every 3 weeks as docetaxel 75 mg/m2 plus doxorubicin 50 mg/m2, or docetaxel 60 mg/m2 plus doxorubicin 60 mg/m2. Phase II studies conducted with these doses in first-line treatment of metastatic breast cancer patients resulted in overall response rates ranging between 57% and 77% with long durations of response. ⋯ Preliminary results reveal a superior overall response rate of 60% with docetaxel plus doxorubicin versus 47% with doxorubicin plus cyclophosphamide (p = .008). Time to disease progression and overall survival results are awaited. The results of these trials, in addition to others being conducted in the adjuvant and the neoadjuvant settings, will establish the ultimate place in therapy for the docetaxel and doxorubicin combination in the management of patients with breast cancer.
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Seminars in oncology · Jun 1999
ReviewSingle-agent docetaxel (Taxotere) in randomized phase III trials.
Until recently, there has been no standard treatment for patients with metastatic breast cancer who have failed an anthracycline-containing regimen, and no definitive phase III trials had been conducted in this setting. The results of three randomized phase III clinical trials of single-agent docetaxel (Taxotere, Rhône-Poulenc Rorer, Collegeville, PA) 100 mg/m2 every 3 weeks in comparison to combination chemotherapy regimens in patients with metastatic breast cancer pretreated with an anthracycline-based chemotherapy regimen are reviewed and reported. An overall response rate of between 30% and 42% was reported for single-agent docetaxel, which was higher in comparison to response rates attained with the combination chemotherapy regimens in all three trials. ⋯ These results firmly establish docetaxel as preferred therapy over combination chemotherapy regimens with mitomycin C plus vinblastine, methotrexate plus 5-fluorouracil, or 5-fluorouracil plus vinorelbine in the therapy of anthracycline-resistant and/or anthracycline-pretreated metastatic breast cancer patients. The results document the continued high level of docetaxel antitumor activity in previously anthracycline-exposed patients initially reported in phase II trials and confirm a substantial lack of anthracycline cross-resistance. The higher response rate of single-agent docetaxel versus single-agent doxorubicin as demonstrated in a fourth randomized phase III trial gives credence to the presumption that the combination of these two agents may provide a highly effective chemotherapy regimen in the management of breast cancer patients.
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Seminars in oncology · Jun 1999
ReviewPhase I-II studies of docetaxel as a single agent in the treatment of metastatic breast cancer.
Docetaxel (Taxotere, Rhône-Poulenc Rorer, Antony, France) is highly effective in the first-line treatment of metastatic breast cancer, achieving an objective response rate of 61% (95% confidence interval, 52% to 69%). This rate of response is seen in patients with poor prognostic factors such as liver metastases and multiple organ involvement. ⋯ Phase II data suggest that docetaxel is the most active agent yet available in the treatment of advanced breast cancer; this conclusion is now supported by the results of randomized phase III trials. These data justify the further investigation of docetaxel alone and in combination chemotherapy.
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Seminars in oncology · Jun 1999
ReviewPhase III randomized trials of docetaxel in patients with metastatic breast cancer.
In a randomized phase III trial in which docetaxel was compared with doxorubicin in metastatic breast cancer patients who had failed prior alkylating chemotherapy, docetaxel proved more active, achieving responses at a significantly higher rate (complete + partial responses, 48% v 33%). The risk to benefit ratio favors docetaxel. The higher response rate was achieved without the risk of potentially fatal cardiac toxicity evident in patients who received doxorubicin and with a lower risk of infection and febrile neutropenia. ⋯ Those assigned to docetaxel lived significantly longer (median survival, 11.4 v 8.7 months), experienced a longer time before disease progression (19 weeks v 11 weeks), and achieved a higher overall response rate (30% v 11.6%). The toxicity profile of both regimens was manageable. These phase III studies confirmed the activity observed with docetaxel in the phase II trials and support the view point that docetaxel is one of the most active agents available for the treatment of breast cancer.
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Seminars in oncology · Jun 1999
ReviewEmerging role of docetaxel (Taxotere) in advanced non-small cell lung cancer.
In the first-line treatment of advanced non-small cell lung cancer (NSCLC), phase II trials of single-agent docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) at a dose of 100 mg/m2 every 3 weeks have reported encouraging results, with an overall response rate of 29% and a median survival duration of 9 months. Neutropenia is the dose-limiting toxicity but, even when severe, is usually of brief duration. Docetaxel also is active against NSCLC at doses of 60 to 75 mg/m2, which are associated with a lower incidence of neutropenia and other side effects. ⋯ In a large multicenter trial of 80 platinum-treated patients, the response rate was 16%, median survival was 7 months, and the 1-year survival rate was 25%. In conclusion, single-agent docetaxel appears to be one of the most active agents in the therapy of advanced NSCLC, with response and survival data in chemonaive patients comparable to that reported for combination chemotherapy regimens and activity in platinum-refractory NSCLC superior to that reported with other agents studied to date. Further studies designed to optimize the therapeutic index of docetaxel and docetaxel-based combination chemotherapy of NSCLC are clearly indicated.