Seminars in oncology
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Seminars in oncology · Apr 2000
Review Comparative StudyPentostatin (Nipent) and chlorambucil with granulocyte-macrophage colony-stimulating factor support for patients with previously untreated, treated, and fludarabine-refractory B-cell chronic lymphocytic leukemia.
Renewed interest in chronic lymphocytic leukemia (CLL) has led to an unprecedented number of investigators contributing to all aspects of research in this disease. In fact, the evolution of research in the area of molecular aberrations in CLL and their impact on treatment resistance alone is striking. These data, along with the advent of the purine analogs, have been central to this paradigm shift. ⋯ Based on preclinical data demonstrating synergistic activity when a DNA damaging agent (eg, an alkylating agent) is followed by an inhibitor of DNA repair (a purine analog), a number of purine analog/alkylator combinations have been and are presently being examined in a variety of lymphoid neoplasms. While the clinical data conflict, at least two phase II studies examining a combination of a purine analog and an alkylator in untreated patients with CLL have generated promising data. This report describes the scientific justification and the design of a new phase II study examining the combination of pentostatin and chlorambucil with granulocyte-macrophage colony-stimulating factor support for patients with untreated, treated, and fludarabine-refractory B-cell CLL.
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Seminars in oncology · Apr 2000
ReviewDocetaxel (Taxotere) in combination with anthracyclines in the treatment of breast cancer.
Considering the single-agent activity of docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) and doxorubicin in breast cancer and their potential non-cross-resistance, several docetaxel/anthracycline-based combination chemotherapies were developed in phase I and II programs for metastatic breast cancer patients. The rationale for these combinations was also reinforced by the fact that docetaxel showed significant activity in phase III trials in patients previously exposed or having failed anthracycline chemotherapy. In a pivotal randomized phase III study of doxorubicin plus docetaxel versus doxorubicin plus cyclophosphamide as first-line chemotherapy for 429 patients with metastatic breast cancer, doxorubicin/docetaxel emerged as the more effective regimen. ⋯ However, there were no septic deaths among 213 patients receiving doxorubicin/ docetaxel. Extrahematologic toxicity appeared mild for both regimens and the combination docetaxel/doxorubicin did not increase the cardiac toxicity expected for an anthracycline-containing regimen. Docetaxel plus doxorubicin is the first regimen, involving a newly developed agent, proven superior to a standard anthracycline-containing combination in metastatic breast cancer and its potential is now being investigated in the adjuvant setting.
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Seminars in oncology · Apr 2000
ReviewDocetaxel (Taxotere) in HER-2-positive patients and in combination with trastuzumab (Herceptin).
In addition to being an important indicator of poor prognosis, human epidermal growth factor receptor-2 (HER-2) status may help identify those patients in whom chemotherapy is the most appropriate choice of therapy. In several studies, including a trial of sequential neoadjuvant therapy in which certain patients received docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) following four courses of cyclophophamide 1000 mg/m2, doxorubicin 50 mg/m2, vincristine 1.5 mg/m2 on day one, and prednisone 40 mg by mouth for 5 days, HER-2 positivity predicted response (including pathologic response) to chemotherapy. ⋯ In a phase III study comparing trastuzumab alone with trastuzumab plus chemotherapy (either paclitaxel or doxorubicin plus cyclophosphamide), combining the antibody with cytotoxic drugs increased response duration, time to progression, and survival in first-line metastatic breast cancer patients. Preliminary clinical data suggest that the combination of trastuzumab with docetaxel is active and well tolerated, and pilot studies of adjuvant therapy using trastuzumab and docetaxel combinations are under way in high-risk patients.
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Seminars in oncology · Apr 2000
ReviewDocetaxel (Taxotere) as a single agent and in combination chemotherapy for the treatment of patients with advanced non-small cell lung cancer.
Docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) has high and reproducible single-agent activity in non-small cell lung cancer, inducing responses in nearly one third of patients treated first-line. As a second-line treatment, docetaxel is the only agent so far shown in randomized trials to prolong survival when compared with either vinorelbine or ifosfamide or best supportive care. When docetaxel is given on a weekly rather than once every 3 week schedule, the risk of neutropenia is reduced while activity appears to be maintained. ⋯ A phase II study of 51 patients treated with the combination of 100 mg/m2 docetaxel and 900 mg/m2 gemcitabine reported a 13-month median survival. In a randomized phase II trial comparing docetaxel/gemcitabine with docetaxel/cisplatin, the two regimens had comparable efficacy and toxicity. Response rates of up to 50% have been reported using docetaxel in conjunction with vinorelbine.