title: A phase I/II study of pemetrexed and vinorelbine in patients with non-small cell lung cancer.
abstract: OBJECTIVE
  Pemetrexed and vinorelbine are active antineoplastic agents in non-small cell lung cancer (NSCLC). Phase I objectives include maximum tolerated dose (MTD) and recommended phase II dose determination, and pharmacokinetics of the pemetrexed-vinorelbine doublet in locally advanced or metastatic solid tumor patients (pts). Phase II objectives include tumor response evaluation, efficacy, and toxicity for first-line treatment of advanced NSCLC.
  
  
  METHODS
  Phase I pts received pemetrexed (day 1, 300-700 mg/m2) and vinorelbine (days 1 and 8, 15-30 mg/m2) every 21 days. Pharmacokinetics determined at cycle 1. Beginning with dose-level 3, folic acid and Vitamin B12 supplementation were given.
  
  
  RESULTS
  Thirty-one phase I pts were enrolled. MTD was pemetrexed 700 mg/m2 and vinorelbine 30 mg/m2; and recommended phase II dose was pemetrexed 500 mg/m2 and vinorelbine 30 mg/m2. When administered in combination, pemetrexed and vinorelbine pharmacokinetics were consistent with single-agent administration. Thirty-seven (36 chemonaive) phase II NSCLC pts received pemetrexed-vinorelbine. Evaluable tumor response was 40%, with intent-to-treat 38%. One drug-related death occurred from febrile neutropenia with Staphylococcal infection. Grade 3/4 hematologic toxicities were neutropenia (65%) and febrile neutropenia (11%), while prevalent grade 3/4 non-hematologic toxicity was fatigue (27%).
  
  
  CONCLUSIONS
  The pemetrexed-vinorelbine combination is well tolerated and shows activity as first-line treatment in advanced NSCLC patients.
authors.affiliation: University of Sydney, Sydney Cancer Centre, Concord Hospital, Hospital Road, Concord, NSW 2139, Australia. sclarke@med.usyd.edu.au
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Clarke
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Boyer
authors.forename: Michael
authors.initials: M
authors.lastname: Millward
authors.forename: Craig
authors.initials: C
authors.lastname: Underhill
authors.forename: Eugene
authors.initials: E
authors.lastname: Moylan
authors.forename: Desmond
authors.initials: D
authors.lastname: Yip
authors.forename: Shane
authors.initials: S
authors.lastname: White
authors.forename: Annabel
authors.initials: A
authors.lastname: Childs
authors.forename: Phillip
authors.initials: P
authors.lastname: Beale
authors.forename: Jane
authors.initials: J
authors.lastname: Latz
authors.forename: Ajit
authors.initials: A
authors.lastname: Suri
authors.forename: Jose L
authors.initials: JL
authors.lastname: Iglesias
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D003404:Creatinine / Q000378:metabolism; D019587:Dietary Supplements; D005260:Female; D005971:Glutamates / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D000068437:Pemetrexed; D013997:Time Factors; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000077235:Vinorelbine; D014805:Vitamin B 12 / Q000494:pharmacology
chemical_list: D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D005971:Glutamates; D000068437:Pemetrexed; D014747:Vinblastine; D006147:Guanine; D003404:Creatinine; D014805:Vitamin B 12; D000077235:Vinorelbine