Seminars in oncology
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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
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: 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
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
Clinical TrialA phase I/II study of sequential doxorubicin and paclitaxel in the treatment of advanced breast cancer.
Based on preclinical data, we designed a phase I/II clinical trial to determine the efficacy and toxicity of doxorubicin followed by paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in the treatment of patients with advanced breast cancer (either untreated or relapsed after adjuvant therapy). In the phase I study, 19 enrolled patients received bolus doxorubicin (50 mg/m2) and, after a 16-hour interval, escalating doses of paclitaxel (from 130 to 250 mg/m2 in 30-mg/ m2 increments) by 3-hour infusion every 3 weeks for a maximum of eight cycles. Paclitaxel doses were increased if the maximum tolerated dose (MTD; defined by dose-limiting toxicities) had not been reached. ⋯ The median durations of objective and complete response were 9 and 7 months, respectively. The 78.9% objective response rate in the phase I trial (31.6% complete and 47.3% partial responses) suggests a dose response relationship: at paclitaxel dose > or = 190 mg/m2, all patients had an objective response (six complete and nine partial responses). These results confirm that doxorubicin followed by paclitaxel is active and should be tested as adjuvant treatment and in patients treated previously with anthracyclines.