A Phase I, open-label, dose-escalation study of continuous once-daily oral treatment with afatinib in patients with advanced solid tumors

Invest New Drugs. 2013 Apr;31(2):409-16. doi: 10.1007/s10637-012-9904-9. Epub 2012 Dec 15.


Background: This trial evaluated the safety, tolerability and maximum tolerated dose (MTD) of afatinib, a novel ErbB Family Blocker.

Methods: In this open-label, dose-escalation Phase I study, afatinib was administered continuously, orally, once-daily for 28 days to patients with advanced or metastatic solid tumors. Dose escalation was performed in a 3 + 3 design, with a starting dose of 10 mg/day (d); doses were doubled for each successive cohort until the MTD was defined. The MTD cohort was expanded to a total of 19 patients. Incidence and severity of adverse events (AEs), antitumor activity and pharmacokinetics were assessed.

Results: Thirty patients received at least one dose of afatinib. Twenty-nine patients were evaluable for response. Dose-limiting toxicities (DLTs) consisting of Grade 3 diarrhea were observed in two out of three patients treated at 60 mg/d. The MTD was determined at 40 mg/d. The most frequent treatment-related AEs were diarrhea and mucosal inflammation reported in 76.7% and 43.3% of patients respectively. Five patients had stable disease with a median progression-free survival of 111 days. No objective responses occurred. Pharmacokinetic data showed no deviation from dose-proportionality and steady-state was reached on Day 8 at the latest.

Conclusions: Afatinib was well tolerated with manageable side effects when administered once-daily, continuously at a dose of 40 mg.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Afatinib
  • Aged
  • Aged, 80 and over
  • Cohort Studies
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasms / drug therapy*
  • Prognosis
  • Quinazolines / pharmacokinetics*
  • Quinazolines / therapeutic use*
  • Tissue Distribution


  • Quinazolines
  • Afatinib