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
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
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
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
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.