title: Sunitinib plus erlotinib for the treatment of advanced/metastatic non-small-cell lung cancer: a lead-in study.
abstract: BACKGROUND
  This randomized, double-blind, multicenter study evaluated sunitinib plus erlotinib versus placebo plus erlotinib. Subjects with advanced non-small-cell lung cancer had received prior treatment with a platinum-based regimen. Here, we report safety, pharmacokinetics, and antitumor activity of the combination of sunitinib and erlotinib.
  
  
  METHODS
  Lead-in subjects in this phase II study received sunitinib 37.5 mg/d and erlotinib 150 mg/d. Safety, including dose-limiting toxicities (DLTs, cohort 1 only), pharmacokinetic profiles, and antitumor activity were investigated (cohorts 1 and 2).
  
  
  RESULTS
  Thirty patients were evaluated. The combination of sunitinib and erlotinib was tolerable. Diarrhea (76.9%), fatigue (61.5%), and decreased appetite (53.8%) were the most frequent adverse events in cohort 1; and diarrhea (52.9%) and rash (41.2%) were the most frequent adverse events in cohort 2. DLTs were observed (fatigue, n = 2 and paronychial inflammation, n = 1) in three of 13 patients evaluated for DLTs. Geometric mean ratios for the maximum plasma concentration (Cmax) and area under plasma concentration-time profile from time 0 to 24 hours of erlotinib with and without sunitinib were 1.05 and 1.03, respectively. Corresponding values for sunitinib with and without erlotinib were 0.62 and 0.62 for sunitinib, 2.13 and 2.07 for SU12662; and 0.81 and 0.79 for total drug. Three patients experienced partial response as per response evaluation criteria in solid tumor.
  
  
  CONCLUSIONS
  A dosage of sunitinib 37.5 mg/d concurrently with erlotinib 150 mg/d was tolerable and established the recommended combinatorial dose in subjects with platinum-refractory non-small-cell lung cancer. Coadministration of sunitinib with erlotinib does not affect the pharmacokinetics of erlotinib, but may result in decreased exposure to sunitinib.
authors: Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030-1402, USA. gblumens@mdanderson.org
authors: George R
authors: GR
authors: Blumenschein
authors: Tudor
authors: T
authors: Ciuleanu
authors: Francisco
authors: F
authors: Robert
authors: Harry J M
authors: HJ
authors: Groen
authors: Tiziana
authors: T
authors: Usari
authors: Ana
authors: A
authors: Ruiz-Garcia
authors: Lesley
authors: L
authors: Tye
authors: Richard C
authors: RC
authors: Chao
authors: Erzsebet
authors: E
authors: Juhasz
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D018287:Carcinoma, Large Cell / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D015331:Cohort Studies; D004311:Double-Blind Method; D000069347:Erlotinib Hydrochloride; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D011758:Pyrroles / Q000008:administration & dosage; D011799:Quinazolines / Q000008:administration & dosage; D000077210:Sunitinib; D015996:Survival Rate; D014018:Tissue Distribution
chemical_list: D007211:Indoles; D011758:Pyrroles; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D000077210:Sunitinib