A Phase I Study of the Hsp90 Inhibitor AUY922 plus Capecitabine for the Treatment of Patients with Advanced Solid Tumors

Cancer Invest. 2015;33(10):477-82. doi: 10.3109/07357907.2015.1069834. Epub 2015 Oct 13.

Abstract

Background: This phase I study determined the maximum tolerated dose (MTD) of AUY922 with capecitabine in advanced solid tumors.

Methods: Capecitabine 1000 mg/m(2) PO BID was administered with escalating doses of AUY922 IV; the MTD of AUY922 was combined with capecitabine 1250 mg/m(2) (DL6).

Results: 23 patients were treated at 5 dose levels (22 mg/m(2)-70 mg/m(2)). No DLTs were observed until DL6 (grade 3 diarrhea). Reversible vision darkening was seen in 26%. Four patients had partial response; 2 previously progressed on fluorouracil. Eight patients had stable disease (median 25.5 weeks).

Conclusion: AUY922 plus capecitabine was well-tolerated up to 70 mg/m(2) with encouraging preliminary efficacy.

Keywords: AUY922; Capecitabine; Hsp90.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Capecitabine / administration & dosage
  • Capecitabine / adverse effects
  • Capecitabine / therapeutic use*
  • Female
  • HSP90 Heat-Shock Proteins / antagonists & inhibitors*
  • HSP90 Heat-Shock Proteins / metabolism
  • Humans
  • Isoxazoles / administration & dosage
  • Isoxazoles / adverse effects
  • Isoxazoles / therapeutic use*
  • Male
  • Middle Aged
  • Neoplasms / drug therapy*
  • Resorcinols / administration & dosage
  • Resorcinols / adverse effects
  • Resorcinols / therapeutic use*

Substances

  • 5-(2,4-dihydroxy-5-isopropylphenyl)-4-(4-morpholin-4-ylmethylphenyl)isoxazole-3-carboxylic acid ethylamide
  • HSP90 Heat-Shock Proteins
  • Isoxazoles
  • Resorcinols
  • Capecitabine