title: Erlotinib and vinorelbine in advanced malignant solid tumors: a phase I study.
abstract: BACKGROUND
  Erlotinib is an oral epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI). Vinorelbine, a vinca alkaloid, interferes with microtubule assembly inhibiting mitosis during metaphase. Both drugs are commonly used as single agents in the treatment of advanced non small cell lung cancer (NSCLC). Given their efficacy in NSCLC and their non-overlapping toxicity profile, we conducted a phase I study of erlotinib and vinorelbine to establish the feasibility and safety of the combination and to determine the maximum tolerated dose (MTD).
  
  
  METHODS
  Patients with advanced solid tumors were treated with vinorelbine intravenously on day 1 and 8 and erlotinib orally daily on a 21 day schedule. The dose levels of vinorelbine/erlotinib were 25 mg/m(2)/100 mg, 25/150 and 30/150.
  
  
  RESULTS
  Sixteen patients were enrolled. Five patients were chemo-naïve; 11 had one prior therapy. The majority of patients had NSCLC (n = 7). Dose limiting toxicities included febrile neutropenia (4 patients) and grade 5 infection (1 patient). Non-hematologic grade 3/4 toxicities included diarrhea, hypokalemia, infection, dyspnea and mucositis. Of 12 patients assessable for radiologic response, there were no objective responses; eight had stable disease.
  
  
  CONCLUSIONS
  (1) The MTD was vinorelbine 25 mg/m2 day 1 and 8 with erlotinib 100 mg/day every 21 days. (2) The combination was associated with high rate of febrile neutropenia (25%). (3) Due to subsequent data demonstrating a lack of efficacy of erlotinib in combination with platinum doublets in advanced NSCLC, this combination has not been explored further.
authors: Davis Cancer Center, University of California, 4501 X Street, Suite 3016, Sacramento, CA 95817, USA. angela.davies@ucdmc.ucdavis.edu
authors: Angela M
authors: AM
authors: Davies
authors: Cheryl
authors: C
authors: Ho
authors: Paul J
authors: PJ
authors: Hesketh
authors: Laurel A
authors: LA
authors: Beckett
authors: Primo N
authors: PN
authors: Lara
authors: Derick H M
authors: DH
authors: Lau
authors: David R
authors: DR
authors: Gandara
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D000069347:Erlotinib Hydrochloride; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D011799:Quinazolines / Q000008:administration & dosage; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine
chemical_list: D011799:Quinazolines; D014747:Vinblastine; D000069347:Erlotinib Hydrochloride; D000077235:Vinorelbine