Pegylated liposomal doxorubicin as first-line monotherapy in elderly women with locally advanced or metastatic breast cancer: novel treatment predictive factors identified

Cancer Lett. 2011 Dec 27;313(2):145-53. doi: 10.1016/j.canlet.2011.07.017. Epub 2011 Aug 31.

Abstract

We investigated the efficacy and safety of single-agent pegylated liposomal doxorubicin (PLD) as first-line treatment for elderly women with advanced breast cancer and evaluated predictive markers for response and toxicity. Twenty-five women ≥ 65 years received 40 mg/m(2) PLD every 28 days. Time to treatment failure (TTF), response rate, time to progression (TTP) and overall survival (OS) was calculated. The ABCB1 single nucleotide polymorphisms (SNP), tumor MRN complex, and TOPOIIα were analyzed. A mean of 7.4 cycles PLD were administered and TTF was 5.5 months and OS 20.6 months. ABCB1 SNPs were found to correlate to both efficacy and toxicity, while tumor expression of the MRN complex and TOPOIIα correlated to TTP. PLD is a safe and effective treatment for elderly breast cancer patients. Also potential predictive markers were identified.

Publication types

  • Clinical Trial, Phase IV
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • Acid Anhydride Hydrolases
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / metabolism
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • DNA Repair Enzymes / metabolism
  • DNA Topoisomerases, Type II / metabolism
  • DNA-Binding Proteins / metabolism
  • Disease Progression
  • Doxorubicin / adverse effects
  • Doxorubicin / analogs & derivatives*
  • Doxorubicin / therapeutic use
  • Female
  • HMGN Proteins / metabolism
  • Humans
  • MRE11 Homologue Protein
  • Polyethylene Glycols / adverse effects
  • Polyethylene Glycols / therapeutic use*
  • Polymorphism, Single Nucleotide
  • Predictive Value of Tests
  • Time Factors
  • Trans-Activators / metabolism
  • Treatment Failure

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • HMGN Proteins
  • HMGN5 protein, human
  • MRE11 protein, human
  • Trans-Activators
  • liposomal doxorubicin
  • Polyethylene Glycols
  • Doxorubicin
  • MRE11 Homologue Protein
  • Acid Anhydride Hydrolases
  • RAD50 protein, human
  • DNA Topoisomerases, Type II
  • DNA Repair Enzymes