Abstract
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. Within this dose range, more prolonged exposure seems to result in higher response rates. 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.
Publication types
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Clinical Trial
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Clinical Trial, Phase I
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Anemia / chemically induced
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Brain Neoplasms / drug therapy
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Brain Neoplasms / radiotherapy*
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Carcinoma, Non-Small-Cell Lung / drug therapy
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Carcinoma, Non-Small-Cell Lung / radiotherapy*
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Carcinoma, Squamous Cell / drug therapy
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Carcinoma, Squamous Cell / radiotherapy*
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Cell Cycle / drug effects
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Combined Modality Therapy
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Dose-Response Relationship, Drug
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Female
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Glioblastoma / drug therapy
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Glioblastoma / radiotherapy*
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Head and Neck Neoplasms / drug therapy
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Head and Neck Neoplasms / radiotherapy*
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Humans
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Infusions, Intravenous
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Lung Neoplasms / drug therapy
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Lung Neoplasms / radiotherapy*
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Lymphopenia / chemically induced
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Paclitaxel / administration & dosage
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Paclitaxel / adverse effects
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Paclitaxel / therapeutic use*
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Radiation-Sensitizing Agents / therapeutic use
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Remission Induction
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Uterine Cervical Neoplasms / drug therapy
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Uterine Cervical Neoplasms / radiotherapy*
Substances
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Radiation-Sensitizing Agents
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Paclitaxel