title: A Phase I dose-escalation study of afatinib combined with nintedanib in patients with advanced solid tumors.
abstract: OBJECTIVE
  To evaluate the safety and maximum tolerated dose (MTD) of afatinib combined with nintedanib.
  
  
  METHODS
  Patients received afatinib 10-20 mg daily plus nintedanib 150-200 mg twice daily (28-day cycle). Dose escalation followed a 3+3 design.
  
  
  RESULTS
  Patients received afatinib/nintedanib: 10/150 mg (n = 11); 10/200 mg (n = 13; MTD); 20/200 mg (n = 4). Four patients had dose-limiting toxicities (all grade 3): increased alanine aminotransferase (afatinib/nintedanib: 10/150 mg), diarrhea (10/200 mg), dehydration (20/200 mg), diarrhea with elevated liver enzymes (20/200 mg). Frequent treatment-related adverse events were diarrhea, nausea, anorexia, fatigue and vomiting. In total, 14 patients (46.2%) had objective responses at the MTD.
  
  
  CONCLUSIONS
  The MTD, afatinib 10 mg daily plus nintedanib 200 mg twice daily, had a manageable safety profile, but was considered subtherapeutic for Phase II evaluation.
authors.affiliation: Pinnacle Oncology Hematology, 9055 E Del Camino, Suite 100, Scottsdale, AZ 85258, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Gordon
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Springett
authors.forename: Yungpo Bernard
authors.initials: YB
authors.lastname: Su
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Ould-Kaci
authors.forename: Sven
authors.initials: S
authors.lastname: Wind
authors.forename: Yihua
authors.initials: Y
authors.lastname: Zhao
authors.forename: Patricia M
authors.initials: PM
authors.lastname: LoRusso
mesh_terms: D000328:Adult; D000077716:Afatinib; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000493:pharmacokinetics; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D011799:Quinazolines / Q000008:administration & dosage / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D007211:Indoles; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000077716:Afatinib; C530716:nintedanib
keywords: BIBF 1120; BIBW 2992; ErbB family blocker; Phase I; afatinib; nintedanib; pharmacokinetics; triple angiokinase inhibitor