Seminars in oncology
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Seminars in oncology · Feb 1996
ReviewPaclitaxel couplets with cyclophosphamide or cisplatin in metastatic breast cancer.
Determining active combinations containing paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) to treat metastatic breast cancer has been the focus of recent clinical development. Paclitaxel combined with either cyclophosphamide or cisplatin has several potential advantages: cisplatin and cyclophosphamide are active single agents against previously untreated metastatic breast cancer, colony-stimulating factors can modulate overlapping toxicities like myelosuppression, and no mechanisms of cross-resistance between paclitaxel and these agents are yet known. Major questions include the optimal schedule of administration and the sequence dependence of toxicities with these combinations. ⋯ As expected, dose-limiting toxicity in all studies has been hematologic. However, granulocyte colony-stimulating factor has ameliorated myelosuppression and allowed considerable dose escalation of cyclophosphamide. This combination has demonstrated activity in previously treated patients with metastatic breast cancer, including the anthracycline-refractory subpopulation that will be reviewed.
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Seminars in oncology · Feb 1996
ReviewRole of paclitaxel in the treatment of breast cancer: the American Cooperative Group Experience.
Phase I and II trials to evaluate paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) as a single agent and combined with other drugs have generated considerable enthusiasm for this interesting new agent. Despite these trials, or because of them, many important questions remain regarding the use of paclitaxel. Ongoing Cooperative Oncology Group trials investigating the use of paclitaxel in breast cancer include CLB 9342, examining the question of paclitaxel dose intensity; the National Surgical Adjuvant Breast Project trial B-26, investigating the question of duration of infusion; E1193, testing the relative activity and synergy of paclitaxel and doxorubicin in a metastatic setting; and CLB 9344, focusing on the adjuvant use of paclitaxel. The cooperative groups are currently investigating novel paclitaxel-based combination therapy in phase II trials.
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Seminars in oncology · Feb 1996
Review Comparative StudyThe role of taxanes in the treatment of breast cancer.
The taxanes paclitaxel and docetaxel are undergoing extensive evaluation in women with breast cancer in the United States and in Europe. Their dose-limiting toxicity is neutropenia. Paclitaxel also causes peripheral neuropathy, while docetaxel can cause unpredictable and severe skin toxicity, as well as edema and effusions due to a capillary leak syndrome. ⋯ These results clearly indicate that the taxanes will become a standard component of initial chemotherapy for women with breast cancer. The definition of their actual role still requires an answer to the unresolved questions of their optimal dose and combination with other anticancer agents. Most importantly, the drugs should be prospectively evaluated in a randomized study using comparable doses and schedules to assess which of the two has the better therapeutic index in breast cancer.
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Seminars in oncology · Feb 1996
ReviewPaclitaxel and doxorubicin, a highly active combination in the treatment of metastatic breast cancer.
The activity of single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has been documented in untreated and previously treated metastatic breast cancer, including both patients with anthracycline-resistant disease and those with extensive pretreatment. Such activity has prompted investigations of the optimal doses and schedules of paclitaxel/doxorubicin combinations. With one exception, paclitaxel has been administered as either a 24- or a 3-hour infusion, while the administration times for doxorubicin vary from bolus injection to 72-hour infusion. ⋯ Cardiotoxicity also occurred, as 15 patients had a significant decrease in left ventricular ejection fraction measured by isotope cardiography. Six of these developed congestive heart failure. This effect has been observed only in studies using short infusions of both drugs, and it is now being investigated whether lowering the peak doxorubicin concentration will preclude it.
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Phase I studies of CPT-11 (irinotecan) have been conducted in Europe, the United States, and Japan to determine the maximum tolerated dose (MTD) and the most appropriate intravenous administration schedule for further evaluation in phase II investigations. Diarrhea and/or neutropenia were the major dose-limiting toxicities in all the phase I studies. In Japanese and US investigations, the CPT-11 MTD was defined as 240 to 250 mg/m2 using a once every 3 weeks schedule and 100 and 150 mg/m2 using a weekly schedule. ⋯ European experience with a single infusion every 3 weeks showed diarrhea to be dose limiting at 350 mg/m2, but concomitant administration of high-dose loperamide allowed administration of CPT-11 at doses of up to 600 mg/m2. This latter schedule was better tolerated, achieved the highest dose intensity, and was considered to confer greater convenience in an outpatient setting when compared with the other European regimens. European phase II studies were therefore commenced using a CPT-11 schedule comprising a single intravenous infusion every 3 weeks at a dose of 350 mg/m2.