Phase 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. 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.
Rosenthal
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DI
University of Texas Southwestern Medical Center, Simmons Cancer Center, Dallas 75235-8593, USA.
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Lucci
J A
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Schold
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Truelson
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Fathallah-Skaykh
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Kamen
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Vuitch
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Gazdar
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Griener
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D000740:Anemia / Q000139:chemically induced; D001932:Brain Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000532:radiotherapy*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000532:radiotherapy*; D002453:Cell Cycle / Q000187:drug effects; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy / Q000532:radiotherapy*; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D008231:Lymphopenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use; D012074:Remission Induction; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*
D011838:Radiation-Sensitizing Agents; D017239:Paclitaxel