Seminars in oncology
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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
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
Comparative StudyPaclitaxel doublets in metastatic breast cancer: Eastern Cooperative Oncology Group and Hoosier Oncology Group Studies.
The recognition of the activity of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in metastatic breast cancer led to attempts to combine this drug with other active agents. Two agents that have received particular attention are doxorubicin and cisplatin. Initial pilot and phase I trials by the Eastern Cooperative Oncology Group (ECOG) led to the development of a three-arm, prospective randomized trial comparing single-agent doxorubicin, single-agent paclitaxel, and the combination of doxorubicin and paclitaxel (E 1193). ⋯ Based on data from Gianni et al (J Clin Oncol 13:2688-2699, 1995), the ECOG is currently involved in two trials attempting both to confirm the superior activity of the regimen used by Gianni et al and, in a phase I/II trial, to ameliorate its cardiac toxicity through the addition of dexrazoxane. Similarly, both the ECOG and the Hoosier Oncology Group were unable to confirm the strikingly positive results obtained by the Vancouver group when cisplatin was combined with paclitaxel (Semin Oncol 22:108-111, 1995 [suppl 6]: Proc Am Soc Clin Oncol 13:71, 1994 [abstr 88]). Indiana University investigators are currently involved in a phase I trial attempting to combine carboplatin and paclitaxel in a biweekly schedule.
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Seminars in oncology · Oct 1996
ReviewPaclitaxel combination therapy in the treatment of metastatic breast cancer.
After the single-agent activity of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) was confirmed, trials to develop a synergistic combination began. Doxorubicin, the most active agent for breast cancer, was studied first. As paclitaxel became more available, other combinations, including high-dose regimens and adjuvant therapies, have been studied. ⋯ Recent and/or ongoing trials are looking at paclitaxel in combination with cisplatin, cyclophosphamide, 5-fluorouracil/ folinic acid, and mitoxantrone combinations, as well as with high-dose regimens and as adjuvant therapy. This review describes a plethora of combination studies finally under way to better define the optimal use of paclitaxel in breast cancer therapies, both as adjuvant treatment and for metastatic disease. Because of the unpredictable nature of drug interactions related to schedule and sequence, ad hoc combinations should not be undertaken outside the context of a well-designed trial.
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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.