title: A phase I, open-label dose-escalation study of continuous treatment with BIBF 1120 in combination with paclitaxel and carboplatin as first-line treatment in patients with advanced non-small-cell lung cancer.
abstract: BACKGROUND
  BIBF 1120 is an oral potent inhibitor of vascular endothelial growth factor receptor, fibroblast growth factor receptor and platelet-derived growth factor receptor, the three key receptor families involved in angiogenesis. This phase I, open-label dose-escalation study investigated BIBF 1120 combined with paclitaxel (Taxol) and carboplatin in first-line patients with advanced (IIIB/IV) non-small-cell lung cancer.
  
  
  METHODS
  Patients received BIBF 1120 (starting dose 50 mg b.i.d.) on days 2-21 and paclitaxel (200 mg/m2) and carboplatin [area under curve (AUC)=6 mg/ml/min] on day 1 of each 21-day cycle. Primary end points were safety and BIBF 1120 maximum tolerated dose (MTD) in this combination. Pharmacokinetics (PK) profiles were evaluated.
  
  
  RESULTS
  Twenty-six patients were treated (BIBF 1120 50-250 mg b.i.d.). BIBF 1120 MTD was 200 mg b.i.d. in combination with paclitaxel and carboplatin. Six dose-limiting toxicity events occurred during treatment cycle 1 (liver enzyme elevations, thrombocytopenia, abdominal pain, and rash). Best responses included 7 confirmed partial responses (26.9%); 10 patients had stable disease. BIBF 1120 200 mg b.i.d. had no clinically relevant influence on the PK of paclitaxel 200 mg/m2 and carboplatin AUC 6 mg/ml/min and vice versa.
  
  
  CONCLUSIONS
  BIBF 1120 MTD was 200 mg b.i.d when given with paclitaxel and carboplatin; this combination demonstrated an acceptable safety profile. No relevant changes in PK parameters of the backbone chemotherapeutic agents or BIBF 1120 were observed.
authors.affiliation: Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora. Electronic address: robert.doebele@ucdenver.edu.
authors.forename: R C
authors.initials: RC
authors.lastname: Doebele
authors.affiliation: US Oncology Research Inc., Houston; Virginia Oncology Associates, Norfolk.
authors.forename: P
authors.initials: P
authors.lastname: Conkling
authors.affiliation: University of Wisconsin Carbone Cancer Center, Madison.
authors.forename: A M
authors.initials: AM
authors.lastname: Traynor
authors.affiliation: Department of Medicine, Ohio State University, Columbus.
authors.forename: G A
authors.initials: GA
authors.lastname: Otterson
authors.affiliation: Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Wind
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Stopfer
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Kaiser
authors.affiliation: Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora.
authors.forename: D R
authors.initials: DR
authors.lastname: Camidge
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood
chemical_list: D007211:Indoles; D016190:Carboplatin; C530716:nintedanib; D017239:Paclitaxel