A phase I dose-escalation and bioavailability study of oral and intravenous formulations of erlotinib (Tarceva, OSI-774) in patients with advanced solid tumors of epithelial origin

Cancer Chemother Pharmacol. 2010 May;66(1):53-8. doi: 10.1007/s00280-009-1133-3. Epub 2009 Dec 3.

Abstract

Purpose: An intravenous (IV) erlotinib formulation has not been characterized in cancer patients but may be useful in those with gastrointestinal abnormalities that impact on the ability to take oral medication. This study sought to determine the maximum tolerated dose (MTD) of erlotinib administered as a single 30-min infusion in patients with advanced solid tumors and absolute bioavailability of erlotinib tablets at matched doses.

Methods: This was a two-center, open label, Phase I, dose-escalation and bioavailability study of single dose IV and oral erlotinib.

Results: The highest escalated IV erlotinib dose achieved was 100 mg, with only mild adverse events reported. The MTD for IV erlotinib was not reached as a predetermined erlotinib plasma concentration cap of 4 microg/mL was exceeded in 3/6 patients. No dose-limiting toxicity was observed. Median bioavailability of erlotinib tablets was 76%.

Conclusions: A 100 mg single IV dose of erlotinib, given as a 30-min infusion, was well tolerated with only minor adverse events and the high level of bioavailability of oral erlotinib was confirmed.

Publication types

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

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Aged
  • Biological Availability
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Erlotinib Hydrochloride
  • Female
  • Humans
  • Infusions, Intravenous
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasms, Glandular and Epithelial / drug therapy*
  • Neoplasms, Glandular and Epithelial / pathology
  • Protein Kinase Inhibitors / administration & dosage*
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / pharmacokinetics
  • Quinazolines / administration & dosage*
  • Quinazolines / adverse effects
  • Quinazolines / pharmacokinetics

Substances

  • Protein Kinase Inhibitors
  • Quinazolines
  • Erlotinib Hydrochloride