title: Phase I dose-escalation study of afatinib, an ErbB family blocker, plus docetaxel in patients with advanced cancer.
abstract: OBJECTIVE
  To determine the maximum tolerated dose (MTD), safety and anti-tumor activity of afatinib combined with docetaxel in advanced cancer.
  
  
  METHODS
  The MTD was determined from dose-limiting toxicities in the first cycle.
  
  
  RESULTS
  Thirty-one patients received 10, 20 and 30 mg oral afatinib, plus 60 and 75 mg/m(2) intravenous docetaxel (six cohorts; 3-week cycles). The MTD of afatinib was 20 mg/day (days 2-21) with 75 mg/m(2) docetaxel (day 1). Dose-limiting toxicities were grade 3/4 diarrhea (n = 3) and febrile neutropenia (n = 6). Most frequently occurring adverse events were diarrhea, neutropenia and rash. Disease stabilization occurred in 14 patients.
  
  
  CONCLUSIONS
  Afatinib 20 mg/day plus docetaxel was suboptimal and the study could not yield Phase II dose recommendations. The combination resulted in a manageable safety profile.
authors: Lombardi Comprehensive Cancer Center, Georgetown University, 3800 Reservoir Road NW, Washington, DC 20007, USA. marshalj@georgetown.edu
authors: John
authors: J
authors: Marshall
authors: Geoffrey I
authors: GI
authors: Shapiro
authors: Martina
authors: M
authors: Uttenreuther-Fischer
authors: Mahmoud
authors: M
authors: Ould-Kaci
authors: Peter
authors: P
authors: Stopfer
authors: Michael S
authors: MS
authors: Gordon
mesh_terms: D000328:Adult; D000077716:Afatinib; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000077143:Docetaxel; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011799:Quinazolines / Q000008:administration & dosage / Q000493:pharmacokinetics; D043823:Taxoids / Q000008:administration & dosage / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D011799:Quinazolines; D043823:Taxoids; D000077143:Docetaxel; D000077716:Afatinib; D066246:ErbB Receptors