Seminars in oncology
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Seminars in oncology · Oct 1996
Randomized Controlled Trial Comparative Study Clinical TrialAn ongoing European organization for research and treatment of cancer crossover trial comparing single-agent paclitaxel and doxorubicin as first- and second-line treatment of advanced breast cancer.
The activity of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in advanced breast cancer patients who have failed doxorubicin treatment is well established, but the optimal sequence between these two important agents remains to be determined. The European Organization for Research and Treatment of Cancer therefore designed a prospective randomized clinical trial in which patients not exposed to anthracyclines in the adjuvant setting received either first-line paclitaxel, given as a 3-hour infusion at a dose of 200 mg/m2 followed at the time of disease progression by second-line doxorubicin, given as a bolus injection at a dose of 75 mg/m2 or the reverse sequence. The target accrual is 330 patients. Interim results on 207 evaluable patients of 289 randomized are presented.
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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 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.