Seminars in oncology
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Seminars in oncology · Oct 1996
ReviewPaclitaxel combination therapy in the treatment of metastatic breast cancer: a review.
Combinations of active antineoplastic agents have been the most effective treatment for metastatic breast cancer. Criteria for an effective combination include use of drugs with different mechanisms of action, nonoverlapping toxic effects, and synergistic, or at least additive, antitumor activity. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), with its unique mechanism of action, offers an excellent opportunity for development of effective combination therapy against breast cancer. ⋯ Combination therapy offers exciting possibilities of enhanced antitumor efficacy. However, given the unexpected and serious toxic effects observed, only proven combinations should be used outside the context of a clinical trial. Additionally, the burden of proof will be to show that these combinations have increased antitumor activity, decreased toxicity, or both compared with single-agent paclitaxel.
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Seminars in oncology · Oct 1996
Randomized Controlled Trial Comparative Study Clinical TrialCyclophosphamide and cisplatin versus paclitaxel and cisplatin: a phase III randomized trial in patients with suboptimal stage III/IV ovarian cancer (from the Gynecologic Oncology Group).
Administration of an alkylating agent plus a platinum coordination complex is standard therapy for advanced epithelial ovarian cancer in the United States. The most commonly used combination is cyclophosphamide/ cisplatin; however, the benefit of this combination in overall survival has not been compelling. We report a prospective comparison of this regimen versus a combination of cisplatin with paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), a new and well-tolerated agent with documented activity in cisplatin-refractory ovarian cancer. ⋯ Progression-free survival was significantly longer (P < .001) with cisplatin/paclitaxel (median, 12.9 v 17.9 months). Overall survival was also significantly longer (P < .001) with cisplatin/paclitaxel (median, 37.5 v 24.4 months). Incorporating paclitaxel into first-line therapy for patients with suboptimally debulked stage III and stage IV ovarian cancer can increase the duration of the progression-free interval and extend overall survival while maintaining an acceptable toxicity profile.
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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 TrialPaclitaxel combined with weekly high-dose 5-fluorouracil/folinic acid and cisplatin in the treatment of advanced breast cancer.
Our phase II study results demonstrating high efficacy and low toxicity for a weekly schedule of high-dose 5-fluorouracil (5-FU)/folinic acid (FA) in intensively pretreated metastatic breast cancer patients prompted the addition of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) to this regimen in a phase I/ II outpatient study. Patients were treated with high-dose 5-FU (by 24-hour infusion) and FA (by 2-hour infusion prior to 5-FU) weekly for 6 weeks (day 1, 8, 15, 22, 29, and 36) repeated every 50 days; in addition, paclitaxel was administered by 3-hour infusion on days 1 and 22. The following dose levels were used in phase 1 of the study. ⋯ Median survival time has not yet been reached. The combination of paclitaxel with weekly high-dose 5-FU/FA was well tolerated in second-line treatment of metastatic breast cancer and results also indicate high efficacy against anthracycline-resistant disease. In an ongoing phase II study we are evaluating the addition of cisplatin to the regimen as first-line treatment of metastatic breast cancer.
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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.