Seminars in oncology
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Seminars in oncology · Aug 1997
ReviewDocetaxel (Taxotere) for the treatment of anthracycline-resistant breast cancer.
Until the introduction of the taxoids, docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) and paclitaxel (Taxol; Bristol-Myers Squibb Oncology, Princeton, NJ), in the 1990s, anthracyclines were widely recognized as the best single agents for the treatment of breast cancer. However, even when anthracyclines are used in combination regimens with response rates of over 50%, including complete responses in 17% of patients, few women (3%) with metastatic disease remain disease free at 5 years after treatment. The low level of sustained responses is largely due to the phenomenon of drug resistance. ⋯ The overall response rate to docetaxel monotherapy in patients with anthracycline-resistant or refractory metastatic disease has been shown to be 41%. The response rate to first-line docetaxel monotherapy for metastatic breast cancer has been shown to be 61%, suggesting that two thirds of the activity of docetaxel is retained in anthracycline-resistant disease. Treatment with a simultaneous combination of docetaxel and doxorubicin has been found to be very active, with a response rate of 89%, and trials to exploit the lack of cross-resistance between these agents, in sequential regimens and adjuvant therapies, are under way.
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Seminars in oncology · Aug 1997
Clinical TrialSeven-week continuous-infusion paclitaxel plus concurrent radiation therapy for locally advanced non-small cell lung cancer: a phase I study.
The goal of this National Cancer Institute-sponsored phase I trial is to determine the feasibility, toxicity, and pharmacokinetics of continuous-infusion (24 hr/d, 7 d/wk, 7 weeks total) intravenous paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) when combined with standard, curative-intent radiation therapy (RT) for previously untreated, locally advanced non-small cell lung cancers. Eligible patients have locally advanced (T4NXM0 or TXN2-3M0) non-small cell cancer ineligible for potentially curative surgical resection, a good performance status, adequate hematologic, hepatic, and renal functions, and no distant metastases. All patients receive a total tumor dose of 64.8 Gy megavoltage RT in 7 weeks at 1.8 Gy once daily, 5 d/wk. ⋯ A slowly progressive normocytic anemia with no renal dysfunction was found to be associated with an acquired hypoerythropoietin state. These findings indicate that this therapy is feasible and well tolerated through current dose levels, with no dose-limiting toxicity. Dose escalation is ongoing.
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Seminars in oncology · Aug 1997
Clinical TrialTwice-weekly paclitaxel and radiation for stage III non-small cell lung cancer.
A phase I study was conducted to investigate the safety and efficacy of twice-weekly paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and concurrent thoracic irradiation in patients with stage III non-small cell lung cancer. Radiation therapy beginning on day 1 was delivered in 1.8- to 2.0-Gy daily fractions, to a total dose of 61 Gy. Paclitaxel at a starting dose of 25 mg/m2/d was administered intravenously over 1 hour before daily radiation on days 1, 4, 8, 11, 15, 18, 22, 25, 29, 32, 36, and 39, for a total of 12 doses over 6 weeks. ⋯ Response rates ranging from 50% to 100% were observed (three of six patients at paclitaxel 25 mg/m2, four of six at 30 mg/m2, seven of seven at 35 mg/m2, six of six at 40 mg/m2), for an overall response rate of 80%. We conclude that the maximum tolerated dose of paclitaxel is 35 mg/m2 given twice weekly in a 1-hour infusion for 6 weeks concurrently with thoracic irradiation. This study provides the basis for an ongoing trial combining twice-weekly paclitaxel and carboplatin with concurrent thoracic irradiation for patients with stage III non-small cell lung cancer.
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Seminars in oncology · Aug 1997
Clinical TrialA phase II study evaluating the efficacy of carboplatin, etoposide, and paclitaxel with granulocyte colony-stimulating factor in patients with stage IIIB and IV non-small cell lung cancer and extensive small cell lung cancer.
We initiated a phase II pilot study to determine whether adding paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) to combination carboplatin/etoposide is tolerable and active in patients with advanced non-small cell lung cancer and extensive small cell lung cancer. Patients were given carboplatin (area under the concentration-time curve of 6) followed by etoposide 80 to 100 mg/m2 intravenously on days 1 through 3 followed by paclitaxel 200 mg/m2 intravenously over 3 hours on day 3. On days 4 through 18, granulocyte colony-stimulating factor 5 microg/kg was administered subcutaneously. ⋯ None of the four patients with non-small cell lung cancer responded to treatment, while six of seven small cell lung cancer patients have obtained major responses to therapy. We have increased the etoposide dose to 100 mg/m2 in subsequent patients. The combination chemotherapy regimen of carboplatin, etoposide, and paclitaxel is tolerable and active in patients with small cell lung cancer.
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Seminars in oncology · Aug 1997
Clinical TrialSecond-line treatment of advanced non-small cell lung cancer with paclitaxel and gemcitabine: a preliminary report on an active regimen.
A phase II study of combination paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ)/gemcitabine was conducted in patients with non-small cell lung cancer (NSCLC) who had failed first-line docetaxel- or cisplatin-based chemotherapy. Eligibility criteria included histologically confirmed measurable stage IIIB or IV NSCLC and previous exposure to docetaxel- or cisplatin-based regimens, World Health Organization performance status between 0 and 2, adequate hematologic parameters, and adequate hepatic, renal, and cardiac function. Gemcitabine (900 mg/m2) was given on days 1 and 8 as a 30-minute infusion; paclitaxel (175 mg/m2) was administered on day 8 as a 3-hour infusion after appropriate premedication. ⋯ Other toxicities were mild to moderate. These preliminary results suggest that the paclitaxel/gemcitabine combination is an active and well-tolerated salvage regimen in patients with NSCLC previously treated with docetaxel- or cisplatin-based chemotherapy. The paclitaxel/gemcitabine combination merits further evaluation as first-line treatment.