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 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 TrialPaclitaxel/carboplatin plus ifosfamide in non-small cell lung cancer.
Chemotherapy has a positive role in managing patients with stage IV non-small cell lung cancer. Randomized studies and meta-analyses comparing chemotherapy with best supportive care have confirmed a significant prolongation of survival for chemotherapy-treated patients. In recent years, several new active agents have been identified. ⋯ Although the three-drug regimens used in the 1980s appeared to be no more active than two-drug combinations, the advent of additional active compounds with novel mechanisms of action allows this question to be readdressed. Based on this background, we have initiated a phase I/II study of carboplatin and paclitaxel with escalating doses of ifosfamide. The study design and dosing schedule are discussed in this report.
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Seminars in oncology · Aug 1997
Clinical TrialPostoperative bronchopulmonary complications in stage III lung cancer patients treated with preoperative paclitaxel-containing chemotherapy and concurrent radiation.
We previously observed encouraging results and acceptable toxicity in phase II trials testing preoperative split-course thoracic radiation and simultaneous cisplatin, etoposide, and 5-fluorouracil in stage III non-small cell lung cancer patients. We decided to delete 5-fluorouracil and to incorporate paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) into our combined-modality treatment. The first group of patients received carboplatin dosed at an area under the concentration-time curve of 4 on day 2, etoposide 50 mg orally days 1 to 5 and 8 to 12, cisplatin 50 mg/m2 on day 21, and paclitaxel 35 mg/m2 escalated to 45 mg/m2 on days 1 and 8. ⋯ Postoperative complications included bronchopleural fistula in one patient each in groups 1 and 3, hypoxia in one patient in group 1, pulmonary hypertension in one patient in group 2, pneumonia in one patient in group 2, and adult respiratory distress syndrome in one patient in group 3, which proved lethal. Thus, six of 16 patients had serious postoperative complications. The relatively high incidence of postoperative bronchopulmonary complications suggests that the use of preoperative paclitaxel-containing chemotherapy and simultaneous thoracic radiation may not be feasible.
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Seminars in oncology · Aug 1997
Clinical TrialPreliminary analysis of a phase II study of paclitaxel, carboplatin, and hyperfractionated radiation therapy for locally advanced inoperable non-small cell lung cancer.
We conducted a prospective phase II study to determine the response rate, toxicity profile, and survival rate among patients with locally advanced unresectable non-small cell lung cancer receiving concurrent weekly paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), carboplatin, and hyperfractionated radiation therapy followed by two cycles of adjuvant paclitaxel and carboplatin. The weekly paclitaxel/carboplatin regimen was designed to optimize the radiosensitizing properties of paclitaxel during the concurrent phase of treatment. Thirty-two patients with unresectable stage IIIA and IIIB non-small cell lung cancer from Vanderbilt Cancer Center Affiliate Network institutions entered the study from June 1996 until February 1997. ⋯ Grade 3 and 4 pulmonary toxicities each occurred in 26% of patients. Thus, weekly paclitaxel/carboplatin plus concurrent hyperfractionated radiotherapy is a well-tolerated outpatient regimen with an encouraging response rate that is at least equivalent to more toxic chemoradiation regimens. These findings indicate that further clinical evaluation of weekly paclitaxel/carboplatin/hyperfractionated radiotherapy is warranted in phase III trials.