title: Intensive radiation therapy concurrent with up to 7-week continuous-infusion paclitaxel for locally advanced solid tumors: phase I studies.
abstract: Patients with locally advanced solid tumors of the lung, head and neck, and malignant astrocytomas usually succumb to their disease despite aggressive standard therapy. Laboratory data suggest that the addition of 1.0 to 10 nmol/L paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), a microtubule stabilizing drug, to radiation therapy may result in significant radiation sensitization, perhaps due to accumulation of cells at G2/M. Relatively low concentrations (1.0 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. The phase I trials reported here are designed to test the combination of paclitaxel, administered by continuous intravenous infusion (24 hours a day, 7 days a week), and standard, curative-intent radiation therapy. The ultimate goal of this study is to improve local and systemic control and survival for patients with these three tumor types. To date, 39 evaluable patients are enrolled in this study; there has been no dose-limiting toxicity up to 6.5 mg/m2/d. Observed toxicities include anemia, lymphopenia, mucositis, and cutaneous toxicities.
authors.affiliation: Department of Radiation Oncology, University of Pennsylvania Medical Center, Philadelphia 19104-4283, USA.
authors.forename: D I
authors.initials: DI
authors.lastname: Rosenthal
authors.forename: O
authors.initials: O
authors.lastname: Okani
authors.forename: J M
authors.initials: JM
authors.lastname: Truelson
authors.forename: H
authors.initials: H
authors.lastname: Fathallah-Shaykh
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
authors.forename: M
authors.initials: M
authors.lastname: Landay
authors.forename: D
authors.initials: D
authors.lastname: Mendelsohn
authors.forename: J
authors.initials: J
authors.lastname: Tourville
authors.forename: L
authors.initials: L
authors.lastname: Hamilton
authors.forename: K Y
authors.initials: KY
authors.lastname: Orr
authors.forename: J
authors.initials: J
authors.lastname: McWhorter
authors.forename: D P
authors.initials: DP
authors.lastname: Carbone
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000532:radiotherapy; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000532:radiotherapy; 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; D017239:Paclitaxel / Q000008:administration & dosage / Q000627:therapeutic use*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018714:Radiotherapy, Adjuvant; D016019:Survival Analysis
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D011838:Radiation-Sensitizing Agents; D017239:Paclitaxel