Randomized Phase II Study ofTwo Doses of Pixantrone in Patients with Metastatic Breast Cancer (NCCTG N1031, Alliance)

Kostandinos Sideras, David W. Hillman, Karthik Giridhar, Brenda F. Ginos, Richard C. Tenglin, Heshan Liu, Beiyun Chen, Winston Tan, Gerald G. Gross, Rex B. Mowat, Amylou C. Dueck, Edith A. Perez, Alvaro Moreno-Aspitia

Research output: Contribution to journalArticlepeer-review


Background: Anthracycline use in metastatic breast cancer (MBC) is hindered by cumulative exposure limits and risk of cardiotoxicity. Pixantrone, a novel aza-anthracenedione with structural similarities to mitoxantrone and anthracyclines, is theorized to exhibit less cardiotoxicity, mainly due to lack of iron binding. We conducted a randomized phase II study to evaluate the efficacy and safety of 2 dosing schedules of pixantrone in patients with refractory HER2-negative MBC. Methods: Intravenous pixantrone was administered at 180 mg/m2 every 3 weeks (group A) versus 85 mg/m2 on days 1, 8, and 15 of a 28-day cycle (group B). Primary endpoint was objective response rate (ORR) and secondary endpoints included progression-free survival (PFS), median 6-month PFS, overall survival (OS), safety, quality of life, and serial assessment of circulating tumor cells. A 20% ORR was targeted as sufficient for further testing of pixantrone in this patient population. Results: Forty-five patients were evaluable, with 2 confirmed partial responses in group A and 1 in group B. The trial was terminated due to insufficient activity. Overall median PFS and OS were 2.8 (95% confidence interval [CI]: 2.0-4.1) and 16.8 (95% CI: 8.9-21.6) months, respectively. Notable overall grade 3-4 adverse events were the following: neutrophil count decrease (62%), fatigue (16%), and decrease in ejection fraction (EF) (4%). Conclusion: Pixantrone has insufficient activity in the second- and third-line MBC setting. It appears, however, to have limited cardiotoxicity. (ClinicalTrials.gov ID: NCT01086605).

Original languageEnglish (US)
Pages (from-to)338-368
Number of pages31
Issue number5
StatePublished - May 2022


  • anthracycline
  • breast cancer
  • cardiotoxicity
  • pixantrone
  • randomized phase II

ASJC Scopus subject areas

  • Medicine(all)


Dive into the research topics of 'Randomized Phase II Study ofTwo Doses of Pixantrone in Patients with Metastatic Breast Cancer (NCCTG N1031, Alliance)'. Together they form a unique fingerprint.

Cite this