Seminars in oncology
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Seminars in oncology · Oct 1996
Clinical TrialA dose-finding study of epirubicin in combination with paclitaxel in the treatment of advanced breast cancer.
We performed a dose escalation study to evaluate the maximum tolerated dose of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) given over 3 hours plus bolus epirubicin 90 mg/m2. The starting dose of paclitaxel, 135 mg/m2, was escalated by 20-mg/m2 increments in cohorts of three to six patients. Courses were repeated every 3 weeks. ⋯ Only two patients showed a decrease of left ventricular ejection fraction below 50% after six courses, and no signs of anthracycline-induced congestive heart failure were noted. The activity of this novel combination is encouraging: the overall response rate is 80%, with 16% complete responses. We have demonstrated that the combination of epirubicin plus paclitaxel given over 3 hours is feasible with acceptable toxicities, does not appear to be associated with clinically relevant cardiotoxicity, and is active in a population of patients who have failed adjuvant chemotherapy.
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Seminars in oncology · Oct 1996
Clinical TrialThe sequential administration of combined doxorubicin and paclitaxel in the treatment of advanced breast cancer.
In phase I and II studies we administered fixed doses of doxorubicin by intravenous bolus 16 hours before escalating doses of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) for the treatment of patients with advanced breast cancer who had received no prior treatment or who had relapsed after adjuvant therapy. Nineteen patients were entered in the study from April 1994 to February 1995. The median age of participants was 54 years; the median disease-free interval was 328 days. ⋯ The maximum tolerated dose was not reached at 250 mg/m2. No cardiac toxicity was reported. The dosing sequence of doxorubicin followed by paclitaxel is a highly active regimen and needs to be tested in anthracycline patients and in an adjuvant setting.
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Seminars in oncology · Oct 1996
Clinical TrialPaclitaxel and carboplatin in metastatic non-small cell lung cancer: preliminary results of a phase I study.
Given their known activity against non-small cell lung cancer, paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin were combined in this phase I study of patients with metastatic disease to determine the maximum tolerated dose and the dose-limiting toxicity of the combination. The initial dose of paclitaxel was fixed at 135 mg/m2 given as a 24-hour infusion with carboplatin administered in escalating doses in cohorts using Calvert's formula-dose (mg) = target AUC x (GFR + 25), where AUC is area under the concentration-time curve and GFR is glomerular filtration rate-based on target AUCs of 5, 7, 9, or 11 mg/mL.min. Dose escalations were based on cycle 1 toxicities. ⋯ Rare nonhematologic toxicities include fatigue, diarrhea, and nausea and vomiting. Among the first 30 patients, one had a complete response and 14 had partial responses, for an overall response rate of 50%. The combination of paclitaxel and carboplatin is active in non-small cell lung cancer, and the recommended phase II dose without filgrastim support is paclitaxel 175 mg/m2 via a 24-hour infusion with the carboplatin dose targeted to achieve an AUC of 7 mg/ mL.min.
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Seminars in oncology · Oct 1996
Doxorubicin and paclitaxel, a highly active combination in the treatment of metastatic breast cancer.
Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is active against advanced breast cancer and anthracycline-resistant breast cancer. We assessed the efficacy and toxicity of doxorubicin followed by a 3-hour infusion of paclitaxel in women with advanced breast cancer. Participants could have received at most one prior adjuvant chemotherapy regimen, but no previous exposure to anthracyclines or taxanes was permitted. ⋯ Main toxicities were neutropenia, paresthesia, nausea/vomiting, alopecia, myalgia, and cardiotoxicity. In 15 patients (50%), the left ventricular ejection fraction decreased to below normal levels; six patients (20%) developed congestive heart failure. In conclusion, the combination of doxorubicin and paclitaxel is highly active; dose-limiting toxicities are neutropenia, neuropathy, and cumulative cardiotoxicity.