A multicenter phase II study of TSU-68, an oral multiple tyrosine kinase inhibitor, in combination with docetaxel in metastatic breast cancer patients with anthracycline resistance

Breast Cancer. 2014 Jan;21(1):20-7. doi: 10.1007/s12282-012-0344-3. Epub 2012 Mar 2.

Abstract

Background: TSU-68 is a novel multiple tyrosine kinase inhibitor that inhibits vascular endothelial growth factor receptor-2, platelet-derived growth factor receptor, and fibroblast growth factor receptor. This open-label, non-comparative, multicenter phase II study evaluated TSU-68 in combination with docetaxel in patients with metastatic breast cancer that had relapsed within 1 year despite prior treatment with an anthracycline-containing regimen.

Methods: TSU-68 was orally administered on days 1-21, and docetaxel was intravenously delivered on day 1. The regimen was repeated every 21 days. Primary endpoint was objective response rate according to the RECIST guidelines version 1.0.

Results: TSU-68 in combination with docetaxel produced objective responses in 21.1% and clinical benefits in 42.1% of the patients, respectively (1 complete response, 3 partial response, and 4 stable disease for at least 24 weeks, n = 19). Median time to progression was 148 days, and median overall survival was 579 days. The common adverse drug reactions were leukopenia, neutropenia, nail disorder, malaise, dysgeusia, alopecia, and edema.

Conclusions: TSU-68 in combination with docetaxel showed a promising antitumor response with manageable toxicity in patients with anthracycline-resistant metastatic breast cancer. Further studies are warranted in a different population of breast cancer or other solid cancers.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Administration, Intravenous
  • Administration, Oral
  • Adult
  • Aged
  • Anthracyclines / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology*
  • Docetaxel
  • Drug Interactions
  • Drug Resistance, Neoplasm*
  • Female
  • Humans
  • Indoles / administration & dosage
  • Indoles / adverse effects
  • Indoles / pharmacokinetics
  • Middle Aged
  • Oxindoles
  • Propionates / administration & dosage
  • Propionates / adverse effects
  • Propionates / pharmacokinetics
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrroles
  • Taxoids / administration & dosage
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / blood

Substances

  • Anthracyclines
  • Indoles
  • Oxindoles
  • Propionates
  • Protein Kinase Inhibitors
  • Pyrroles
  • Taxoids
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Docetaxel
  • orantinib