title: Phase I studies of continuous-infusion paclitaxel given with standard aggressive radiation therapy for locally advanced solid tumors.
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.
authors.affiliation: University of Texas Southwestern Medical Center, Simmons Cancer Center, Dallas 75235-8593, USA.
authors.forename: D I
authors.initials: DI
authors.lastname: Rosenthal
authors.forename: L G
authors.initials: LG
authors.lastname: Close
authors.forename: J A
authors.initials: JA
authors.lastname: Lucci
authors.forename: S C
authors.initials: SC
authors.lastname: Schold
authors.forename: J
authors.initials: J
authors.lastname: Truelson
authors.forename: H
authors.initials: H
authors.lastname: Fathallah-Skaykh
authors.forename: B
authors.initials: B
authors.lastname: Kamen
authors.forename: F M
authors.initials: FM
authors.lastname: Vuitch
authors.forename: A F
authors.initials: AF
authors.lastname: Gazdar
authors.forename: J
authors.initials: J
authors.lastname: Griener
mesh_terms: 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*
chemical_list: D011838:Radiation-Sensitizing Agents; D017239:Paclitaxel