Seminars in oncology
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Seminars in oncology · Aug 1999
Clinical TrialCombination therapy with trastuzumab (Herceptin) and cisplatin for chemoresistant metastatic breast cancer: evidence for receptor-enhanced chemosensitivity.
The anti-HER-2/neu antibody trastuzumab (Herceptin; Genentech, San Francisco, CA) interferes with DNA repair induced by cisplatin and, as a result, promotes cytotoxicity in HER-2/neu-overexpressing tumor target cells in a synergistic fashion. This effect of trastuzumab, termed receptor-enhanced chemosensitivity, is specific for HER-2/neu-overexpressing cells, having no effect on cells without overexpression. Based on these findings, we conducted phase I and II clinical trials of trastuzumab plus cisplatin to determine the toxicity, pharmacokinetics, response rate, and response duration of this combination in patients with HER-2/neu-overexpressing metastatic breast cancer who had demonstrated disease progression (chemoresistance) while on active chemotherapy just prior to study entry. ⋯ Moreover, the pharmacokinetics of trastuzumab were unaltered by coadministration of cisplatin. We conclude that the combination of trastuzumab and cisplatin results in response rates higher than that reported for either single agent alone. Such receptor-enhanced chemosensitivity offers a new approach to target overexpressed growth factor receptors in a variety of cancers, which will lead to new, biologically based therapeutic strategies for clinical intervention.
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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
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.