Reference Detail

Contact

Missing content? – Request curation!

Request curation for specific Genes, Variants, or PubMed publications.

Have questions, comments, or suggestions? - Let us know!

Email us at : ckbsupport@jax.org

Ref Type Journal Article
PMID (21576284)
Authors Soria JC, Cortes J, Massard C, Armand JP, De Andreis D, Ropert S, Lopez E, Catteau A, James J, Marier JF, Beliveau M, Martell RE, Baselga J
Title Phase I safety, pharmacokinetic and pharmacodynamic trial of BMS-599626 (AC480), an oral pan-HER receptor tyrosine kinase inhibitor, in patients with advanced solid tumors.
Journal Vol Issue Date Pages Journal Short Title
Annals of oncology : official journal of the European Society for Medical Oncology 23 2 2012 Feb 463-71 Ann Oncol
URL
Abstract Text We studied the safety, tolerability, and recommended dose of BMS-599626, an orally bioavailable inhibitor of the human epidermal growth factor receptor (HER) family of receptor tyrosine kinases.Patients with advanced solid tumors that expressed epidermal growth factor receptor (EGFR) and/or HER-2 were recruited and enrolled in a phase I, open-label, dose escalation trial of oral BMS-599626 starting at 100 mg/day given once daily for at least 28 days.Forty-five patients received BMS-599626 (100-660 mg/day). Dose-limiting toxic effects were reported at 660 mg/day (grade 3 elevation of hepatic transaminases [two patients] and QTc interval prolongation [one patient]), therefore the recommended maximum tolerated dose was 600 mg/day. The most frequent drug-related toxic effects were diarrhea (30% of patients), anorexia (13%), asthenia (30%), and cutaneous toxic effects, including skin rash (30%). Pharmacokinetic analysis demonstrated C(max) and exposure to BMS-599626 in patients increased with dose. Eleven patients had stable disease and received BMS-599626 for ≥ 4 months. Serial skin and tumor biopsies taken before and after treatment revealed expected changes in pharmacodynamic biomarkers, indicating that the EGFR and HER-2 pathways were affected. Positron emission tomography imaging showed a metabolic response in 2 of 10 patients evaluated.BMS-599626 was generally well tolerated, with disease stabilization across a range of tumor types and doses.

Filtering

  • Case insensitive filtering will display rows if any text in any cell matches the filter term
  • Use simple literal full or partial string matches
  • Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page. Filtering has no impact on query parameters.
  • Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")

Sorting

  • Generally, the default sort order for tables is set to be first column ascending; however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column. Be sure to set ascending or descending order for a given column before moving on to the next column.

Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
AC480 AC480 0 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
AC480 BMS-599626|AC-480 EGFR Inhibitor (Pan) 61 HER2 Inhibitor 41 AC480 (BMS-599626) is an inhibitor of EGFR and ERBB2 (HER2), which may prevent downstream signaling and inhibit the proliferation of tumor cells that overexpress these receptors (PMID: 17062696, PMID: 21576284).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References