Skip to main content

Advertisement

Log in

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

  • Original Article
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

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 μg/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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Moyer JD, Barbacci EG, Iwata KK et al (1997) Induction of apoptosis and cell cycle arrest by CP-358, 774, an inhibitor of epidermal growth factor receptor tyrosine kinase. Cancer Res 57:4838–4848

    CAS  PubMed  Google Scholar 

  2. Frohna P, Lu J, Eppler S, Hamilton M, Wolf J, Rakhit A et al (2006) Evaluation of the absolute oral bioavailability and bioequivalence of erlotinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in a randomized, crossover study in healthy subjects. J Clin Pharmacol 46:282–290

    Article  CAS  PubMed  Google Scholar 

  3. Hughes Andrew ERM, O’Brien W, Petty J, Chick J, Rankin E et al (2009) Overcoming CYP1A1/1A2 mediated induction of metabolism by escalating erlotinib dose in current smokers. JCO 27:1220–1226. doi:10.1200/JCO.2008.19.3995

    Article  CAS  Google Scholar 

  4. Hamilton M, Wolf JL, Rusk J, Beard SE, Clark GM, Witt K, Cagnoni PJ (2006) Effects of smoking on the pharmacokinetics of erlotinib. Clin Cancer Res 12:2166–2171

    Article  CAS  PubMed  Google Scholar 

  5. Hidalgo M, Siu LL, Nemunaitis J et al (2001) Phase I and pharmacological study of OSI-774, an epidermal growth factor receptor tyrosine kinase inhibitor, in patients with advanced solid malignancies. J Clin Oncol 19:3267–3279

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Authors Shaw, Reid and Judson gratefully acknowledge the support of the National Institute for Health Research, London, UK.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to M. Ranson.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ranson, M., Shaw, H., Wolf, J. et al. 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 66, 53–58 (2010). https://doi.org/10.1007/s00280-009-1133-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00280-009-1133-3

Keywords

Navigation