Seminars in oncology
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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.
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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
ReviewDocetaxel and anthracycline polychemotherapy in the treatment of breast cancer.
Given the single-agent activity of docetaxel and doxorubicin in metastatic breast cancer and their potential non-cross-resistance, several phase I/II pilot studies of either docetaxel/doxorubicin (TA) or TA plus cyclophosphamide (TAC) were conducted. The results of these studies show that the main toxicity is related to neutropenia and its consequences, although documented infections are rarely reported. Other toxicities are mild, while docetaxel-specific toxicities (fluid retention, nail changes, etc) are seldom seen. ⋯ In terms of efficacy, response rates in the range of 70% to 80% were noted in all studies, even for patients with visceral metastases. Preliminary data suggest that the combination of docetaxel with epirubicin is also feasible, with manageable toxicities and significant activity. Several phase III randomized trials using TA or TAC are presently being performed in first-line metastatic breast cancer and, most importantly, in the adjuvant setting to assess whether TA-based combinations will change the natural history of breast cancer.
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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.