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dc.contributor.authorDent, R.
dc.contributor.authorLindeman, G.
dc.contributor.authorClemons, M.
dc.contributor.authorWildiers, H.
dc.contributor.authorChan, Arlene
dc.contributor.authorMcCarthy, N.
dc.contributor.authorSinger, C.
dc.contributor.authorLowe, E.
dc.contributor.authorWatkins, C.
dc.contributor.authorCarmichael, J.
dc.date.accessioned2017-01-30T11:46:34Z
dc.date.available2017-01-30T11:46:34Z
dc.date.created2015-10-29T04:09:51Z
dc.date.issued2013
dc.identifier.citationDent, R. and Lindeman, G. and Clemons, M. and Wildiers, H. and Chan, A. and McCarthy, N. and Singer, C. et al. 2013. Phase I trial of the oral PARP inhibitor olaparib in combination with paclitaxel for first- or second-line treatment of patients with metastatic triple-negative breast cancer. Breast Cancer Research. 15 (5).
dc.identifier.urihttp://hdl.handle.net/20.500.11937/14874
dc.identifier.doi10.1186/bcr3484
dc.description.abstract

Introduction: This Phase I study evaluated the safety, tolerability and efficacy of olaparib, a potent oral poly(ADP-ribose) polymerase (PARP) inhibitor, in combination with paclitaxel in patients with metastatic triple-negative breast cancer (mTNBC). Methods: Eligible patients who had received =1 prior cytotoxic regimen for mTNBC were treated with olaparib 200 mg bid continuously plus weekly paclitaxel 90 mg/m2 for three weeks per four-week cycle. Dose modifications in a large proportion of patients due to neutropenia resulted in enrollment of a second cohort of patients who, if they experienced grade =2 neutropenia in cycle 1, received granulocyte-colony stimulating factor, which was continued prophylactically in subsequent cycles. All patients had measurable disease; tumor responses were evaluated according to RECIST (version 1.0). Results:Nineteen patients (cohort 1, n = 9; cohort 2, n = 10) received treatment; 15 had received prior taxane chemotherapy. The most frequent adverse events were diarrhea (n = 12, 63%), nausea (n = 11, 58%) and neutropenia (n = 11, 58%). Seven neutropenia events were reported in cohort 1 (four grade =3) and four in cohort 2 (two grade =3, including one event of febrile neutropenia). The median (range) dose intensity of paclitaxel was 57% (26 to 100%) in cohort 1 and 73% (29 to 100%) in cohort 2. Seven patients (37%) had a confirmed partial response; one patient remains on olaparib monotherapy without progression. Conclusions: The combination of olaparib and weekly paclitaxel was complicated by a significant clinical interaction, with higher-than-expected rates of neutropenia despite secondary prophylaxis. Given the encouraging response rate, alternative scheduling and dosing strategies should be considered (funded by AstraZeneca; ClinicalTrials.gov, NCT00707707). © 2013 Dent et al.; licensee BioMed Central Ltd.

dc.titlePhase I trial of the oral PARP inhibitor olaparib in combination with paclitaxel for first- or second-line treatment of patients with metastatic triple-negative breast cancer
dc.typeJournal Article
dcterms.source.volume15
dcterms.source.number5
dcterms.source.issn1465-5411
dcterms.source.titleBreast Cancer Research
curtin.departmentCentre for Population Health Research
curtin.accessStatusOpen access via publisher


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