Brostallicin versus doxorubicin as first-line chemotherapy in patients with advanced or metastatic soft tissue sarcoma: an European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group randomised phase II and pharmacogenetic study

Eur J Cancer. 2014 Jan;50(2):388-96. doi: 10.1016/j.ejca.2013.10.002. Epub 2013 Nov 8.


Aim: Brostallicin is a DNA minor groove binder that has shown activity in patients with soft tissue sarcoma (STS) failing first-line therapy. The present study assessed the safety and efficacy of first-line brostallicin in patients with advanced or metastatic STS >60 years or not fit enough to receive combination chemotherapy. A prospective explorative pharmacogenetic analysis was undertaken in parallel.

Methods: Patients were randomised in a 2:1 ratio between IV brostallicin 10mg/m(2) and doxorubicin 75 mg/m(2) once every 3 weeks for a maximum of six cycles. Disease stabilisation at 26 weeks (primary end-point) was considered a 'success'. Further testing of brostallicin was warranted if ≥ 35 'successes' were observed in the first 72 eligible patients treated with brostallicin. In addition, patients were genotyped for glutathione S transferase (GST) polymorphisms.

Results: One hundred and eighteen patients were included (79 brostallicin and 39 doxorubicin). Brostallicin was well tolerated in comparison to doxorubicin with less grade 3-4 neutropenia (67% versus 95%), grade 2-3 systolic dysfunction (0% versus 11%), alopecia (17% versus 61%) and grade 2-3 mucositis (0% versus 18%). For brostallicin versus doxorubicin, 'successes' were observed in 5/77 versus 10/36, progression free survival at 1 year was 6.5% versus 15.6%, objective response rate was 3.9% versus 22.2% and overall survival at 1 year was 50.5% versus 57.9%, respectively. Only GSTA1 genotype was significantly associated with success rate of doxorubicin treatment.

Conclusion: Brostallicin cannot be recommended at this dose and schedule in this patient population as first-line therapy. GSTA1 genotype may be predictive for doxorubicin efficacy but warrants further study.

Trial registration: NCT00410462.

Keywords: Brostallicin; Doxorubicin; GST; Randomised phase II study; Soft tissue sarcoma.

Publication types

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

MeSH terms

  • Adult
  • Antibiotics, Antineoplastic / therapeutic use
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / genetics
  • Bone Neoplasms / pathology
  • Disease-Free Survival
  • Doxorubicin / therapeutic use*
  • Drug Administration Schedule
  • Europe
  • Gene Frequency
  • Genotype
  • Glutathione Transferase / genetics
  • Guanidines / therapeutic use*
  • Humans
  • Isoenzymes / genetics
  • Kaplan-Meier Estimate
  • Middle Aged
  • Neoplasm Metastasis
  • Pharmacogenetics
  • Polymorphism, Genetic
  • Pyrroles / therapeutic use*
  • Sarcoma / drug therapy*
  • Sarcoma / genetics
  • Sarcoma / pathology
  • Treatment Outcome


  • Antibiotics, Antineoplastic
  • Guanidines
  • Isoenzymes
  • Pyrroles
  • Doxorubicin
  • Glutathione Transferase
  • glutathione S-transferase alpha
  • brostallicin

Associated data