title: Phase I open-label study of continuous treatment with BIBF 1120, a triple angiokinase inhibitor, and pemetrexed in pretreated non-small cell lung cancer patients.
abstract: BACKGROUND
  BIBF 1120 (planned brand name Vargatef) is a novel, oral, triple angiokinase inhibitor targeting three receptor classes involved in blood vessel formation. The objectives of this phase I, open-label dose-escalation study were to determine the safety, tolerability, and maximum tolerated dose (MTD) of BIBF 1120 with pemetrexed in patients with recurrent advanced-stage non-small cell lung carcinoma.
  
  
  METHODS
  Patients harboring a tumor of any non-small cell lung carcinoma histology, previously treated with one first-line platinum-based chemotherapy regimen, received a BIBF 1120 starting dose of 100 mg bid (days 2-21) with pemetrexed 500 mg/m2 (day 1) over a 21-day cycle. Previous pemetrexed treatment was not permitted. BIBF 1120 dose was escalated until the MTD was determined.
  
  
  RESULTS
  Twenty-six patients were treated. During treatment cycle (TC) 1, dose-limiting toxicities were experienced by one patient receiving 100 mg bid, one patient receiving 150 mg bid, one patient receiving 200 mg bid, and two patients receiving 250 mg bid BIBF 1120. Two additional dose-limiting toxicities were observed in TC 1 in an expanded patient cohort receiving 200 mg bid. Gastrointestinal disorders (84.6%), general disorders, and administration site conditions (76.9%) were the most frequent drug-related adverse events. One patient had a complete response 44 days after initiating trial medication; 50% had stable disease as the best overall response. No clinically relevant pharmacokinetic interactions between BIBF 1120 and pemetrexed were observed.
  
  
  CONCLUSIONS
  The MTD of BIBF 1120 in combination with standard-dose pemetrexed was 200 mg bid. Continuous daily treatment with BIBF 1120 in this combination was tolerable, with promising signs of efficacy.
authors.affiliation: Juravinski Cancer Centre, Hamilton, Ontario, Canada. Peter.Ellis@jcc.hhsc.ca
authors.forename: Peter M
authors.initials: PM
authors.lastname: Ellis
authors.forename: Rolf
authors.initials: R
authors.lastname: Kaiser
authors.forename: Yihua
authors.initials: Y
authors.lastname: Zhao
authors.forename: Peter
authors.initials: P
authors.lastname: Stopfer
authors.forename: Steve
authors.initials: S
authors.lastname: Gyorffy
authors.forename: Nasser
authors.initials: N
authors.lastname: Hanna
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005971:Glutamates / Q000008:administration & dosage / Q000009:adverse effects; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D000068437:Pemetrexed
chemical_list: D005971:Glutamates; D007211:Indoles; D000068437:Pemetrexed; D006147:Guanine; C530716:nintedanib