Seminars in oncology
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Seminars in oncology · Dec 1995
Review Clinical TrialCombined-modality therapy for advanced non-small cell lung cancer: paclitaxel and thoracic irradiation.
Despite advances in the modalities used to treat non-small cell lung cancer (NSCLC), the frequency of locoregional and distant relapses necessitates further enhancement of the therapeutic program. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has demonstrated clinical efficacy against NSCLC and in vitro studies support its role as a radiation potentiator at concentrations achievable in vivo. Thus, a phase I study of weekly paclitaxel and daily concurrent thoracic radiation was conducted in patients with advanced NSCLC to determine (1) the maximum tolerated dose of paclitaxel administered on an outpatient basis for 6 consecutive weeks with daily radiation and (2) the toxicities of the paclitaxel/radiation combination. ⋯ The schedule of weekly paclitaxel and daily thoracic radiation appears active in NSCLC and can be delivered safely in the outpatient setting. The principal dose-limiting toxicity is esophagitis, and the maximum tolerated dose of paclitaxel for this schedule is 60 mg/m2/wk. A phase II trial of weekly paclitaxel 60 mg/m2 and radiation has been initiated in patients with NSCLC.
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Seminars in oncology · Dec 1995
ReviewThe role of paclitaxel in the management of coelomic epithelial carcinoma of the ovary: a review with emphasis on the Gynecologic Oncology Group experience.
Coelomic epithelial carcinoma of the ovary, the most common cause of death from cancer of the female genital tract in the United States, presents most commonly as advanced (stage III or IV) disease. Management consists of aggressive surgical cytoreduction followed by combination chemotherapy, until recently, a platinum compound plus an alkylating agent. The recent identification of the activity of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) offers the potential to improve further the management of patients with advanced disease. ⋯ The results show the superiority of the paclitaxel/cisplatin regimen: overall response rate 77% versus 62%, clinical complete response 54% versus 33%, frequency of achieving a grossly disease-free state at second-look laparotomy 40% versus 22%, progression-free survival 18 versus 13 months, and overall survival 38 versus 24 months. Thus, paclitaxel/cisplatin is the new standard of care for patients with advanced ovarian carcinoma. Current phase III studies explore further the role of paclitaxel in front-line therapy: the relative merits of single-agent versus combination chemotherapy, the role of interval surgical cytoreduction combined with paclitaxel/cisplatin, the value of carboplatin-based versus cisplatin-based combinations with paclitaxel, the significance of the paclitaxel infusion length (3 v 24 v 96 hours), and the value of more dose-intense combinations.
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Seminars in oncology · Dec 1995
Comparative Study Clinical Trial Controlled Clinical TrialPaclitaxel in lung cancer: 1-hour infusions given alone or in combination chemotherapy.
Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) given as a 1-hour infusion potentially offers its recipients reduced toxicity, demonstrated efficacy, and greater ease of administration. To confirm this hypothesis, we undertook a phase I/II study of 1-hour, single-agent paclitaxel in 164 patients' refractory malignancies; 59 patients with recurrent or stage IV non-small cell lung cancer (NSCLC) participated in the study. Our objective was to compare two paclitaxel doses (135 and 200 mg/m2) and two 1-hour infusion schedules (1 hour in 1 day, or 1 hour each day for 3 days, divided dose). ⋯ Of the 22 patients now evaluable for response (median follow-up, 8 months), 10 (six with limited and four with extensive small cell lung cancer) have achieved CRs and 11 have achieved partial remissions. The regimen is well tolerated. The final results of these and other phase II trials should help clarify optimal paclitaxel schedules and regimens for large-scale randomized trials in patients with lung cancer.
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Seminars in oncology · Dec 1995
Sequential adjuvant therapy with doxorubicin/paclitaxel/cyclophosphamide for resectable breast cancer involving four or more axillary nodes.
The results of both retrospective and prospective studies suggest that the effectiveness of systemic adjuvant chemotherapy with doxorubicin and cyclophosphamide for breast cancer may be related to the dose intensity of these agents. Recent trials also have demonstrated the high activity of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) against metastatic breast cancer. Clinically, paclitaxel appears to be noncross-resistant with doxorubicin, but the unique and overlapping toxicities of these three agents might preclude concurrent adjuvant administration. ⋯ The median follow-up from local control surgery in December 1994 was 448 days (range, 82 to 632 days). Three patients (7.2%) had disease relapses, one during the doxorubicin portion of treatment and two (4.9%) who had completed treatment with all three agents. Sequential dose-intensive therapy with doxorubicin/paclitaxel/cyclophosphamide has manageable toxicity and, with short follow-up, is a promising new regimen suitable for randomized testing.
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Seminars in oncology · Dec 1995
Clinical Trial Controlled Clinical TrialA phase I/II trial of combination paclitaxel and carboplatin in advanced or metastatic non-small cell lung cancer: preliminary results of an ongoing study.
Because of paclitaxel's (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) high single-agent activity in non-small cell lung cancer we developed a study to determine the maximum tolerated dose and a dose suitable for outpatient phase II/III trials of paclitaxel combined with a fixed dose of carboplatin (area under the concentration-time curve of 6, Calvert formula). From October 1993 to November 1994, 41 patients were entered into this trial, including six at dose level I (paclitaxel 150 mg/m2), six at dose level 2 (paclitaxel 175 mg/m2), II at dose level 3 (paclitaxel 200 mg/m2), 13 at dose level 4 (paclitaxel 225 mg/m2), and five at dose level 5 (paclitaxel 250 mg/m2). Patient characteristics included 27 men and 14 women with a median age of 64 years (age range, 46 to 81 years). ⋯ The maximum tolerated dose was defined at the 250 mg/m2 dose level with three of five patients achieving grade 3 (severe toxicity. The 225 mg/m2 dose level appears to be well tolerated, but accrual at this dose level is ongoing. This appears to be a highly active regimen, with objective responses in 20 (two complete responses and 18 partial responses) of 32 patients with objectively measurable disease for an overall response rate of 62.5%.