TY - JOUR
T1 - Randomized Phase II Study ofTwo Doses of Pixantrone in Patients with Metastatic Breast Cancer (NCCTG N1031, Alliance)
AU - Sideras, Kostandinos
AU - Hillman, David W.
AU - Giridhar, Karthik
AU - Ginos, Brenda F.
AU - Tenglin, Richard C.
AU - Liu, Heshan
AU - Chen, Beiyun
AU - Tan, Winston
AU - Gross, Gerald G.
AU - Mowat, Rex B.
AU - Dueck, Amylou C.
AU - Perez, Edith A.
AU - Moreno-Aspitia, Alvaro
N1 - Funding Information:
This study was sponsored by CTIBIOPHARMA. This study was conducted as a collaborative trial of North Cancer Center Treatment Group-Alliance for Clinical Trials in Oncology, the Nacional Cancer Institute and the Mayo Clinic and was supported in part by Public Health Service grants U10CA180821 and U10CA025224 from the National Cancer Institute Department of Health and Human Services. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. ClinicalTrials.gov Identifier: NCT01086605.
Publisher Copyright:
© The Author(s) 2022. Published by Oxford University Press.
PY - 2022/5
Y1 - 2022/5
N2 - 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).
AB - 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).
KW - anthracycline
KW - breast cancer
KW - cardiotoxicity
KW - pixantrone
KW - randomized phase II
UR - http://www.scopus.com/inward/record.url?scp=85144209985&partnerID=8YFLogxK
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U2 - 10.1093/oncolo/oyab065
DO - 10.1093/oncolo/oyab065
M3 - Article
C2 - 35445723
AN - SCOPUS:85144209985
VL - 27
SP - 338
EP - 368
JO - Oncologist
JF - Oncologist
SN - 1083-7159
IS - 5
ER -