Seminars in oncology
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Seminars in oncology · Aug 1995
Clinical TrialPaclitaxel and carboplatin with and without filgrastim support in patients with metastatic non-small cell lung cancer.
Paclitaxel (Taxol; Bristol-Myers Squibb Oncology, Princeton, NJ) and carboplatin have each shown activity against non-small cell lung cancer and they are synergistic in vitro. We thus designed a phase I study to define the maximum tolerated dose and dose-limiting toxicity of the combination with and without filgrastim support. With an initial fixed dose of paclitaxel 135 mg/m2 given as a 24-hour infusion, carboplatin was administered in escalating doses in cohorts of three patients, based on a target area under the concentration-time curve (AUC) of 5, 7, 9, or 11 using Calvert's formula: dose (mg) = target AUC x (glomerular filtration rate + 25). ⋯ There is a suggestion of a dose-response effect with both paclitaxel and carboplatin. The combination of paclitaxel and carboplatin is active in non-small cell lung cancer, and the recommended phase II doses for the combination without filgrastim support are paclitaxel 175 mg/m2 as a 24-hour infusion with the carboplatin dose based on a target AUC of 7. The phase II dose with filgrastim support will be defined as dose escalation of paclitaxel continues.
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Seminars in oncology · Aug 1995
Clinical TrialPhase I studies of continuous-infusion paclitaxel given with standard aggressive radiation therapy for locally advanced solid tumors.
Currently available therapies are unsatisfactory for locally advanced solid tumors of the lung, head and neck, and brain. Laboratory data suggest that the addition of paclitaxel (Taxol; Bristol-Myers Squibb Oncology, Princeton, NJ), a microtubule-stabilizing drug, to radiation therapy may result in significant radiation sensitization, perhaps because paclitaxel induces cell cycle arrest at G2/M. Relatively low concentrations, 1 to 10 nmol/L, appear to be optimal for direct cytotoxicity and radiosensitization in vitro. ⋯ We are conducting phase I trials designed to test continuous infusion (24 hours per day, 7 days per week) intravenous paclitaxel combined with standard curative-intent radiation therapy. To date, 22 patients are evaluable, and the maximum tolerated dose of paclitaxel has not been reached at up to 2.5 mg/m2/d. Observed toxicities include anemia, lymphopenia, mucositis, and cutaneous erythema/desquamation.
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Seminars in oncology · Aug 1995
Clinical TrialConcurrent paclitaxel/cisplatin with thoracic radiation in patients with stage IIIA/B non-small cell carcinoma of the lung.
Nine patients with stage IIIB non-small cell lung cancer were entered into a phase II trial designed to determine the feasibility of giving a combination of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) plus cisplatin concurrent with thoracic radiation. Paclitaxel was given as a 24-hour infusion (135 mg/m2) followed by cisplatin (75 mg/m2) every 4 weeks, for a total of four cycles. Thoracic radiation was given concurrently with the first two cycles of chemotherapy, for a total dose of 64.8 Gy over 6 weeks. ⋯ All patients were able to receive the full dose of radiation, although half of the patients required some modification of the chemotherapy regimen. There was one complete response and four partial responses, yielding a 56% overall response rate. This study demonstrates that it is feasible to treat patients with stage IIIB non-small cell lung cancer with paclitaxel/cisplatin plus concurrent thoracic radiation, with a degree of toxicity comparable with that associated with a degree of toxicity comparable with that associated with other concurrent combined-modality regimens for this disease.
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Seminars in oncology · Jun 1995
ReviewNew treatment agents for advanced small cell and non-small cell lung cancer.
The cure rate for lung cancer remains low (13%) primarily due to early systemic spread and the inability to cure systemic disease. These facts have led to pessimism regarding the role of chemotherapy, especially in non-small cell lung cancers. ⋯ Early combination studies show even higher response rates when paclitaxel is combined with cisplatin or carboplatin. Ultimately, randomized trials will be needed to define the optimal use of paclitaxel and other recently developed new agents in lung cancer.
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Seminars in oncology · Jun 1995
ReviewEastern Cooperative Oncology Group studies of paclitaxel and doxorubicin in advanced breast cancer.
Based on their single-agent activity in metastatic breast cancer, paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and doxorubicin have been alternated and combined in Eastern Cooperative Oncology Group studies to identify a tolerable dose and schedule. A pilot trial in patients who had received no more than one prior chemotherapy regimen alternated paclitaxel 200 mg/m2 and doxorubicin 75 mg/m2 every 3 weeks. Seven of 12 patients had objective (complete plus partial) responses. ⋯ This combination has been incorporated as a treatment arm in an ongoing randomized prospective phase III Intergroup trial. By comparing the combination with both drugs as single agents (with crossover to the opposite agent at disease progression), investigators will attempt to assess response, toxicity, and time to progression as well as the degree of cross-resistance between the two agents. Given the poor prognosis of patients with advanced breast cancer, the three arms also will be evaluated in terms of patients' quality of life.