Seminars in oncology
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Seminars in oncology · Feb 1996
Clinical TrialPreclinical and clinical study results of the combination of paclitaxel and 5-fluorouracil/folinic acid in the treatment of metastatic breast cancer.
Results of phase II studies have demonstrated high efficacy and low toxicity for a weekly schedule of high-dose 5-fluorouracil/folinic acid (5-FU/FA) when given to intensively pretreated patients with metastatic breast cancer. In a phase I/II study of outpatients, we have added paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) to this regimen in an attempt to improve the results. Patients were treated weekly for 6 weeks (days 1, 8, 15, 22, 29, and 36) with high-dose 5-FU 2.0 g/m2 by 24-hour infusion with FA 500 mg/m2 given as a 2-hour infusion prior to 5-FU. ⋯ Median time to progression was 10 months (range, 3 to 17 months). In conclusion, the combination of paclitaxel with weekly high-dose 5-FU/FA is well tolerated as second-line treatment of metastatic breast cancer, with high activity, even in patients with anthracycline-resistant disease. The regimen can be administered safely on an outpatient basis.
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Seminars in oncology · Feb 1996
Paclitaxel-containing combination chemotherapy for metastatic breast cancer.
After demonstration of the marked antitumor activity against metastatic breast cancer of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), other clinical trials explored the possibility of combining this new active agent with other cytotoxic drugs with proven efficacy against breast carcinoma. Paclitaxel plus doxorubicin, thought to be the most effective single agents against breast cancer, yielded remission rates ranging from 60% to 80%, including some complete remissions. Schedule-dependent toxic interactions were observed when paclitaxel preceded the administration of doxorubicin. ⋯ Of interest are recent reports on paclitaxel and vinorelbine, showing this combination to be clearly active, with good tolerability and rapid recovery after myelosuppression. Trials of this combination are ongoing with granulocyte colony-stimulating factor support, on an every-14-day schedule. The doxorubicin/paclitaxel doublet remains the most promising in terms of activity, although other combinations with a high degree of activity and good tolerance are being sought.
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Seminars in oncology · Dec 1995
ReviewTreatment of metastatic breast cancer with paclitaxel and doxorubicin.
The activity of single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) against untreated and previously treated metastatic breast cancer (documented in anthracycline-resistant disease and in extensively pretreated patients as well) has prompted investigations of the optimal doses and schedules of paclitaxel/doxorubicin combinations. With one exception, paclitaxel has been administered in either a 24- or a 3-hour infusion, while the administration times for doxorubicin vary from bolus injection to a 72-hour infusion. Results of these completed phase I and II trials are reviewed. ⋯ Despite grades 3 and 4 neutropenia in 31% and 60% of courses, respectively, only six patients have been hospitalized for febrile neutropenia. Of concern, the left ventricular ejection fraction has decreased to below normal in six patients and two have developed symptomatic congestive heart failure. Whether lowering the peak doxorubicin concentration will preclude this effect, which has been observed only in the studies using short infusions of both drugs, is under investigation.
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Seminars in oncology · Dec 1995
Clinical TrialPhase I/II study of paclitaxel plus cisplatin as first-line chemotherapy for advanced non-small cell lung cancer: preliminary results.
From March 1993 to May 1994, 32 chemotherapy-naive patients with advanced non-small cell lung cancer entered a phase I/II study to determine the maximum tolerated dose and the activity of the paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ)/cisplatin combination. The 21 men and 11 women had a median age of 59 years (range, 25 to 72 years) and a median performance status of 1 (range, 0 to 2). Histologic types were adenocarcinoma (13 cases), squamous cell carcinoma (10), and large cell carcinoma (nine). ⋯ In conclusion, at these doses of paclitaxel and cisplatin, the dose-limiting neurologic toxicity is dose dependent and cumulative after a total paclitaxel dose of approximately 1,300 mg/m2. This combination is highly active, with a total objective response rate of 38% and an objective response rate of 47% at paclitaxel doses of 200 mg/m2 or higher. Further evaluation is warranted.
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Seminars in oncology · Dec 1995
Review Clinical TrialCombined-modality therapy for advanced non-small cell lung cancer: paclitaxel and thoracic irradiation.
Despite advances in the modalities used to treat non-small cell lung cancer (NSCLC), the frequency of locoregional and distant relapses necessitates further enhancement of the therapeutic program. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has demonstrated clinical efficacy against NSCLC and in vitro studies support its role as a radiation potentiator at concentrations achievable in vivo. Thus, a phase I study of weekly paclitaxel and daily concurrent thoracic radiation was conducted in patients with advanced NSCLC to determine (1) the maximum tolerated dose of paclitaxel administered on an outpatient basis for 6 consecutive weeks with daily radiation and (2) the toxicities of the paclitaxel/radiation combination. ⋯ The schedule of weekly paclitaxel and daily thoracic radiation appears active in NSCLC and can be delivered safely in the outpatient setting. The principal dose-limiting toxicity is esophagitis, and the maximum tolerated dose of paclitaxel for this schedule is 60 mg/m2/wk. A phase II trial of weekly paclitaxel 60 mg/m2 and radiation has been initiated in patients with NSCLC.