title: Phase I Study of Oral Vinorelbine in Combination with Erlotinib in Advanced Non-Small Cell Lung Cancer (NSCLC) Using Two Different Schedules.
abstract: This study aimed to evaluate the safety, tolerability and pharmacokinetics of the combination of oral vinorelbine with erlotinib using the conventional (CSV) and metronomic (MSV) dosing schedules in patients with advanced non-small cell lung cancer (NSCLC).
  
  
  
  This was an open-label, multiple dose-escalation phase I study. An alternating 3+3 phase I design was employed to allow each schedule to enroll three patients sequentially at each dose level. Thirty patients with Stage IIIB/IV NSCLC were treated with escalating doses of oral vinorelbine starting at 40 mg/m2 on day 1 and 8 in the CSV group (N = 16) and at 100 mg/week in the MSV group (N = 14). Erlotinib was administered orally daily.
  
  
  
  The maximum tolerated dose was vinorelbine 80 mg/m2 with erlotinib 100 mg in the CSV group and vinorelbine 120 mg/week with erlotinib 100 mg in the MSV group. Grade 3/4 toxicities included neutropenia (N = 2; 13%) and hyponatremia (N = 1; 6%) in the CSV group, and neutropenia (N = 5; 36%) in the MSV group. Objective response was achieved in 38% and 29% in the CSV and MSV groups respectively. Vinorelbine co-administration did not significantly affect the pharmacokinetics of erlotinib and OSI-420 after initial dose. However, at steady-state, significantly higher Cmax, higher Cmin and lower CL/F of erlotinib were observed with increasing dose levels of vinorelbine in the CSV group. Significantly higher steady-state Cmin, Cavg and AUCss of erlotinib were observed with increasing dose levels of vinorelbine in the MSV group.
  
  
  
  Combination of oral vinorelbine with erlotinib is feasible and tolerable in both the CSV and MSV groups.
  
  
  
  ClinicalTrials.gov NCT00702182.
authors.affiliation: Clinical Pharmacology, Singapore Health Services, Singapore, Singapore.
authors.forename: Natalia
authors.initials: N
authors.lastname: Sutiman
authors.affiliation: Clinical Pharmacology, Singapore Health Services, Singapore, Singapore.
authors.forename: Zhenxian
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Division of Medical Oncology, National Cancer Center, Singapore, Singapore.
authors.forename: Eng Huat
authors.initials: EH
authors.lastname: Tan
authors.affiliation: Division of Medical Oncology, National Cancer Center, Singapore, Singapore.
authors.forename: Mei Kim
authors.initials: MK
authors.lastname: Ang
authors.affiliation: Division of Medical Oncology, National Cancer Center, Singapore, Singapore.
authors.forename: Shao-Weng Daniel
authors.initials: SW
authors.lastname: Tan
authors.affiliation: Division of Medical Oncology, National Cancer Center, Singapore, Singapore.
authors.forename: Chee Keong
authors.initials: CK
authors.lastname: Toh
authors.affiliation: Division of Medical Oncology, National Cancer Center, Singapore, Singapore.
authors.forename: Quan Sing
authors.initials: QS
authors.lastname: Ng
authors.affiliation: Clinical Pharmacology, Singapore Health Services, Singapore, Singapore.|Division of Medical Sciences, National Cancer Center, Singapore, Singapore.|Office of Clinical Sciences, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Balram
authors.initials: B
authors.lastname: Chowbay
authors.affiliation: Division of Medical Oncology, National Cancer Center, Singapore, Singapore.|Office of Clinical Sciences, Duke-NUS Graduate Medical School, Singapore, Singapore.|Institute of Molecular and Cell Biology, A*STAR, Singapore, Singapore.
authors.forename: Wan-Teck
authors.initials: WT
authors.lastname: Lim
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D004334:Drug Administration Schedule; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011799:Quinazolines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000077235:Vinorelbine
chemical_list: C487471:OSI-420; D011799:Quinazolines; D014747:Vinblastine; D000069347:Erlotinib Hydrochloride; D000077235:Vinorelbine