Show simple item record

dc.contributor.authorJones, RL
dc.contributor.authorWagner, AJ
dc.contributor.authorKawai, A
dc.contributor.authorTamura, K
dc.contributor.authorShahir, A
dc.contributor.authorVan Tine, BA
dc.contributor.authorMartín-Broto, J
dc.contributor.authorPeterson, PM
dc.contributor.authorWright, J
dc.contributor.authorTap, WD
dc.date.accessioned2021-05-25T13:27:56Z
dc.date.available2021-05-25T13:27:56Z
dc.date.issued2021-02-25
dc.identifier.citationClinical cancer research : an official journal of the American Association for Cancer Research, 2021
dc.identifier.issn1078-0432
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4581
dc.identifier.eissn1557-3265
dc.identifier.eissn1557-3265en_US
dc.identifier.doi10.1158/1078-0432.ccr-20-4592
dc.identifier.doi10.1158/1078-0432.ccr-20-4592en_US
dc.description.abstractPurpose Few prospective studies have assessed anthracycline-associated cardiotoxicity in patients with sarcoma. We evaluated cardiotoxicity in patients with soft-tissue sarcomas administered doxorubicin in the phase III ANNOUNCE trial (NCT02451943).Patients and methods Patients were anthracycline-naïve adults with locally advanced or metastatic disease and left ventricular ejection fraction (LVEF) ≥50%. Patients could receive eight cycles of doxorubicin at 75 mg/m<sup>2</sup>. The cardioprotectant, dexrazoxane, was allowed at investigator discretion. Symptomatic cardiac adverse events (AEs) were recorded using Medical Dictionary for Regulatory Activities and graded using Common Terminology Criteria for Adverse Events 4.0. LVEF deterioration was measured by echocardiogram or multigated acquisition scan, defined as a decrease to <50%, or decrease from baseline value >10%.Results A total of 504 patients received ≥1 cycles of doxorubicin [median cumulative dose, 450.3 mg/m<sup>2</sup> (range, 72.3-634.0)]. Median follow-up of cardiac AEs was 28 weeks. Dexrazoxane was coadministered more frequently to patients receiving higher cumulative doxorubicin doses (38.6% receiving <450 mg/m<sup>2</sup>, 88.5% receiving 450-<600 mg/m<sup>2</sup>, and 90% receiving ≥600 mg/m<sup>2</sup>) and did not affect treatment efficacy. LVEF deterioration was seen in 62 of 153 (40.5%) patients who received a cumulative dose <450 mg/m<sup>2</sup>, 82 of 159 patients (51.6%) who received 450-<600 mg/m<sup>2</sup>, and 50 of 89 patients (56.2%) who received ≥600 mg/m<sup>2</sup>. Grade ≥3 cardiac dysfunction occurred in 2% of patients at <450 mg/m<sup>2</sup>, 3% at 450-<600 mg/m<sup>2</sup>, and 1.1% at ≥600 mg/m<sup>2</sup>. Incidence of treatment-related cardiac AEs was low across all dose ranges.Conclusions Although follow-up was short, these results suggest doxorubicin can be administered at high cumulative doses (>450 mg/m<sup>2</sup>), with a low rate of cardiotoxicities, in the context of dexrazoxane coadministration.
dc.formatPrint-Electronic
dc.languageeng
dc.language.isoeng
dc.rights.urihttp://www.rioxx.net/licenses/all-rights-reserved
dc.titleProspective Evaluation of Doxorubicin Cardiotoxicity in Patients with Advanced Soft-tissue Sarcoma Treated in the ANNOUNCE Phase III Randomized Trial.
dc.typeJournal Article
dcterms.dateAccepted2021-02-22
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1158/1078-0432.ccr-20-4592
rioxxterms.licenseref.startdate2021-02-25
rioxxterms.licenseref.startdate2021-02-25en_US
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfClinical cancer research : an official journal of the American Association for Cancer Research
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Sarcoma Clinical Trials (R Jones)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Sarcoma Clinical Trials (R Jones)/Sarcoma Clinical Trials (R Jones) (hon.)
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Sarcoma Clinical Trials (R Jones)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Sarcoma Clinical Trials (R Jones)/Sarcoma Clinical Trials (R Jones) (hon.)
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished
pubs.embargo.termsNot known
icr.researchteamSarcoma Clinical Trials (R Jones)
icr.researchteamSarcoma Clinical Trials (R Jones)en_US
dc.contributor.icrauthorJones, Robinen


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record