Phase I dose-finding and pharmacokinetic study of the oral epidermal growth factor receptor tyrosine kinase inhibitor Ro50-8231 (erlotinib) in Japanese patients with solid tumors

Cancer Chemother Pharmacol. 2008 Mar;61(3):489-96. doi: 10.1007/s00280-007-0494-8. Epub 2007 May 5.


Purpose: The objectives of this phase I dose-finding study of erlotinib were to investigate the toxicity profile, to confirm the acceptable toxicity of doses up to 150 mg/day, and to assess the pharmacokinetic (PK) profile and antitumor activity in Japanese patients with solid tumors.

Patients and methods: Patients with solid tumors not amenable to standard forms of treatment were included. Treatment cycle 1 consisted of single-dose administration on day 1, withdrawal on day 2, continuous daily administration from days 3-23, and withdrawal from days 24-30. Subsequent cycles (28 days) used continuous daily administration. The dose of erlotinib was escalated from 50 mg/day to 150 mg/day in 50-mg increments. PK evaluation was performed in all patients during cycle 1.

Results: Fifteen patients, aged 38-70 (median; 57) years with non-small-cell lung (n = 11), colorectal (n = 3) or head and neck (n = 1) cancer were enrolled. The major toxicities were rash, diarrhea and liver dysfunctions, which were generally mild and easily manageable. The good tolerability of erlotinib up to the dose of 150 mg/day was confirmed. One patient developed grade 5 treatment-related interstitial pneumonitis. Four of 11 evaluable patients achieved partial responses; all four had non-small-cell lung cancer (NSCLC). The peak plasma concentration of erlotinib, and the area under the concentration-time curve increased proportionally to the dose, suggesting linear PK.

Conclusion: The recommended dose of erlotinib in Japanese patients is 150 mg/day. Further trials in Japanese NSCLC patients are warranted.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Adult
  • Aged
  • Area Under Curve
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / administration & dosage*
  • Enzyme Inhibitors / pharmacokinetics*
  • Enzyme Inhibitors / therapeutic use
  • ErbB Receptors / antagonists & inhibitors*
  • Erlotinib Hydrochloride
  • Female
  • Follow-Up Studies
  • Half-Life
  • Humans
  • Japan
  • Lung Neoplasms / drug therapy
  • Male
  • Middle Aged
  • Neoplasms / complications
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Quinazolines / administration & dosage*
  • Quinazolines / pharmacokinetics*
  • Quinazolines / therapeutic use


  • Enzyme Inhibitors
  • Quinazolines
  • Erlotinib Hydrochloride
  • ErbB Receptors