Seminars in oncology
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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
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.
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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 Trial Controlled Clinical TrialPreliminary results of a phase I study of weekly paclitaxel infusion in patients with non-small cell lung cancer.
Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has a broad spectrum of activity, but the optimal schedule has not yet been determined. As a phase-specific agent, more frequent administration theoretically may be more effective. We have previously demonstrated that a weekly schedule of paclitaxel used as a radiation sensitizer is well tolerated by outpatients. ⋯ Others remain in active treatment. We conclude that the maximum tolerated dose of paclitaxel administered for 6 consecutive weeks of an 8-week cycle is 175 mg/m2/wk and is limited principally by neutropenia. The response rate with this schedule is encouraging and merits further investigation.
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Seminars in oncology · Oct 1996
Clinical TrialPaclitaxel in the treatment of patients with upper gastrointestinal carcinomas.
New agents active against unresectable metastatic and locoregional carcinoma of the esophagus or stomach are needed to improve patient outcomes. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) appears to be active against both adenocarcinoma and squamous cell carcinoma of the esophagus. A phase II study of paclitaxel 250 mg/m2 administered by 24-hour intravenous infusion every 21 days with granulocyte colony-stimulating factor (5 micrograms/kg/d subcutaneously 24 hours following paclitaxel) was conducted in such patients who had received no prior chemotherapy or biologic therapy. ⋯ Anderson Cancer Center exploring the single-agent activity of paclitaxel 200 mg/m2 every 21 days without routine granulocyte colony-stimulating factor in previously untreated patients suggest definite, albeit low-level, activity against gastric carcinoma. Only one PR and three minor responses occurred among the first 15 patients who received paclitaxel in a 3-hour infusion. When the paclitaxel infusion was extended to 24 hours in this ongoing trial, three of the next 10 evaluable patients achieved a PR, with toxicity similar to that observed in other trials of paclitaxel at this dose range.