Skip to main content
construction release_alert
Scholars@Duke will be undergoing maintenance April 11-15. Some features may be unavailable during this time.
cancel

Study of the biologic effects of lapatinib, a reversible inhibitor of ErbB1 and ErbB2 tyrosine kinases, on tumor growth and survival pathways in patients with advanced malignancies.

Publication ,  Journal Article
Spector, NL; Xia, W; Burris, H; Hurwitz, H; Dees, EC; Dowlati, A; O'Neil, B; Overmoyer, B; Marcom, PK; Blackwell, KL; Smith, DA; Koch, KM ...
Published in: J Clin Oncol
April 10, 2005

PURPOSE: This was a pilot study to assess the biologic effects of lapatinib on various tumor growth/survival pathways in patients with advanced ErbB1 and/or ErbB2-overexpressing solid malignancies. PATIENTS AND METHODS: Heavily pretreated patients with metastatic cancers overexpressing ErbB2 and/or expressing ErbB1 were randomly assigned to one of five dose cohorts of lapatinib (GW572016) administered orally once daily continuously. The biologic effects of lapatinib on tumor growth and survival pathways were assessed in tumor biopsies obtained before and after 21 days of therapy. Clinical response was determined at 8 weeks. RESULTS: Sequential tumor biopsies from 33 patients were examined. Partial responses occurred in four patients with breast cancer, and disease stabilization occurred in 11 others with various malignancies. Responders exhibited variable levels of inhibition of p-ErbB1, p-ErbB2, p-Erk1/2, p-Akt, cyclin D1, and transforming growth factor alpha. Even some nonresponders demonstrated varying degrees of biomarker inhibition. Increased tumor cell apoptosis (TUNEL) occurred in patients with evidence of tumor regression but not in nonresponders (progressive disease). Clinical response was associated with a pretreatment TUNEL score > 0 and increased pretreatment expression of ErbB2, p-ErbB2, Erk1/2, p-Erk1/2, insulin-like growth factor receptor-1, p70 S6 kinase, and transforming growth factor alpha compared with nonresponders. CONCLUSION: Lapatinib exhibited preliminary evidence of biologic and clinical activity in ErbB1 and/or ErbB2-overexpressing tumors. However, the limited sample size of this study and the variability of the biologic endpoints suggest that further work is needed to prioritize biomarkers for disease-directed studies, and underscores the need for improved trial design strategies in early clinical studies of targeted agents.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Clin Oncol

DOI

ISSN

0732-183X

Publication Date

April 10, 2005

Volume

23

Issue

11

Start / End Page

2502 / 2512

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Quinazolines
  • Oncology & Carcinogenesis
  • Neoplasms
  • Middle Aged
  • Male
  • Lapatinib
  • In Situ Nick-End Labeling
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Spector, N. L., Xia, W., Burris, H., Hurwitz, H., Dees, E. C., Dowlati, A., … Bacus, S. (2005). Study of the biologic effects of lapatinib, a reversible inhibitor of ErbB1 and ErbB2 tyrosine kinases, on tumor growth and survival pathways in patients with advanced malignancies. J Clin Oncol, 23(11), 2502–2512. https://doi.org/10.1200/JCO.2005.12.157
Spector, Neil L., Wenle Xia, Howard Burris, Herbert Hurwitz, E Claire Dees, Afshin Dowlati, Bert O’Neil, et al. “Study of the biologic effects of lapatinib, a reversible inhibitor of ErbB1 and ErbB2 tyrosine kinases, on tumor growth and survival pathways in patients with advanced malignancies.J Clin Oncol 23, no. 11 (April 10, 2005): 2502–12. https://doi.org/10.1200/JCO.2005.12.157.
Spector, Neil L., et al. “Study of the biologic effects of lapatinib, a reversible inhibitor of ErbB1 and ErbB2 tyrosine kinases, on tumor growth and survival pathways in patients with advanced malignancies.J Clin Oncol, vol. 23, no. 11, Apr. 2005, pp. 2502–12. Pubmed, doi:10.1200/JCO.2005.12.157.
Spector NL, Xia W, Burris H, Hurwitz H, Dees EC, Dowlati A, O’Neil B, Overmoyer B, Marcom PK, Blackwell KL, Smith DA, Koch KM, Stead A, Mangum S, Ellis MJ, Liu L, Man AK, Bremer TM, Harris J, Bacus S. Study of the biologic effects of lapatinib, a reversible inhibitor of ErbB1 and ErbB2 tyrosine kinases, on tumor growth and survival pathways in patients with advanced malignancies. J Clin Oncol. 2005 Apr 10;23(11):2502–2512.

Published In

J Clin Oncol

DOI

ISSN

0732-183X

Publication Date

April 10, 2005

Volume

23

Issue

11

Start / End Page

2502 / 2512

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Quinazolines
  • Oncology & Carcinogenesis
  • Neoplasms
  • Middle Aged
  • Male
  • Lapatinib
  • In Situ Nick-End Labeling