title: Ifosfamide, vinorelbine and gemcitabine in advanced non-small cell lung cancer. A phase I study.
abstract: The objective of this phase I study was to identify the maximum tolerated dose (MTD) and toxicity of a three drug, platinum-free regimen, including gemcitabine, ifosfamide and vinorelbine, in the treatment of patients with advanced non-small cell lung cancer (NSCLC). 33 chemotherapy-naïve patients with histologically confirmed, unresectable NSCLC, received fixed doses of ifosfamide (1500 mg/m2 days 1-3 with mesna) and vinorelbine (25 mg/m2 days 3 and 8). The gemcitabine dose was escalated from 500 to 1200 mg/m2 on days 3 and 8 every third week. The escalation was stopped at dose level 4 (gemcitabine 1200 mg/m2) since all 3 patients of this cohort showed dose-limiting thrombocytopenia and/or neutropenia at treatment cycle 1. The dose recommended for phase II trials is: gemcitabine 1000 mg/m2 and vinorelbine 25 mg/m2 given on days 3 and 8 plus ifosfamide 1500 mg/m2 on days 1-3. An encouraging response rate of 50% (95% confidence interval (CI): 32-68%) was observed in 32 patients evaluated. Our results show that ifosfamide, vinorelbine and gemcitabine can be safely administered as outpatient chemotherapy for NSCLC. Myelosuppression is the dose-limiting toxicity (DLT) of this regimen with no major subjective side-effects observed.
authors.affiliation: University of L'Aquila, Italy. franre@ermes.it
authors.forename: F
authors.initials: F
authors.lastname: Recchia
authors.forename: S
authors.initials: S
authors.lastname: De Filippis
authors.forename: M
authors.initials: M
authors.lastname: Rosselli
authors.forename: P
authors.initials: P
authors.lastname: Pompili
authors.forename: G
authors.initials: G
authors.lastname: Guerriero
authors.forename: S
authors.initials: S
authors.lastname: Rea
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D014747:Vinblastine; D000077235:Vinorelbine; D007069:Ifosfamide; D000093542:Gemcitabine