title: Paclitaxel and ifosfamide: a multicenter phase I study in advanced non-small cell lung cancer.
abstract: Both paclitaxel and ifosfamide have significant single-agent activity in non-small cell lung cancer. We designed a phase I study combining escalating doses of paclitaxel, administered by 24-hour infusion, with ifosfamide given at a dose of 1.6 g/m2 daily x 3. Paclitaxel dose levels were 135, 170, 200, 250, and 300 mg/m2. The goal of the study was to determine the maximum tolerated dose and dose-limiting toxicities of paclitaxel when used in this combination. Dose escalation was possible because of the use of filgrastim, a granulocyte colony-stimulating factor. Twenty-five patients at three institutions were treated. The dose-limiting toxicity of the combination was granulocytopenia, with other toxicities being generally mild to moderate. The maximum tolerated dose of paclitaxel was 300 mg/m2, and the recommended phase II dose is 250 mg/m2. There was a suggestion of a dose-response curve with paclitaxel as all three partial responses were seen at the 250 mg/m2 dose level. An additional II patients had objective regression or stable disease lasting for 9 to 30 weeks. A phase II study of this combination is currently being planned by the Cancer and Leukemia Group B.
authors.affiliation: Department of Medicine, University of Chicago, IL 60637, USA.
authors.forename: P C
authors.initials: PC
authors.lastname: Hoffman
authors.forename: S A
authors.initials: SA
authors.lastname: Krauss
authors.forename: L C
authors.initials: LC
authors.lastname: Drinkard
authors.forename: G A
authors.initials: GA
authors.lastname: Masters
authors.forename: B L
authors.initials: BL
authors.lastname: Samuels
authors.forename: J D
authors.initials: JD
authors.lastname: Bitran
authors.forename: H M
authors.initials: HM
authors.lastname: Golomb
authors.forename: S
authors.initials: S
authors.lastname: Watson
authors.forename: E E
authors.initials: EE
authors.lastname: Vokes
mesh_terms: D000328:Adult; D000368:Aged; D000380:Agranulocytosis / Q000139:chemically induced / Q000517:prevention & control; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D017322:Clinical Trials, Phase II as Topic; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage* / Q000009:adverse effects; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects; D011994:Recombinant Proteins / Q000627:therapeutic use; D012074:Remission Induction
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D017239:Paclitaxel; D000069585:Filgrastim; D007069:Ifosfamide