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
MetadataShow full item record
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.
Showing items related by title, author, creator and subject.
Phase II, open-label trial of lapatinib and vinorelbine in women with previously treated HER2-positive metastatic breast cancerChan, Arlene; Shannon, C.; De Boer, R.; Baron-Hay, S.; Redfern, A.; Bauwens, A.; Craft, P.; Webb, S.; Townsend, A.; Kotasek, D. (2014)Aim: To evaluate the efficacy and tolerability of lapatinib (L) and intravenous vinorelbine (V) in patients with metastatic HER2-positive breast cancer who have previously received two lines of anti-HER2 therapy (i.e. ...
Phase II study of a triple combination of oral vinorelbine, capecitabine and trastuzumab as first-line treatment in HER2-positive metastatic breast cancerChan, Arlene; Conte, P.; Petruzelka, L.; Tubiana-Mathieu, N.; Ganju, V.; Llombart, A.; Espie, M.; Majois, F.; Gil, M.; Vaissiere, N.; Villanova, G. (2013)Chemotherapy plus trastuzumab is the standard first-line treatment for Human Epidermal Receptor 2-positive (HER2-positive) metastatic breast cancer. The aim of this international phase II trial was to determine the efficacy ...
Turner, Sian Elizabeth (2009)Background and research questions. The characterization of chronic persistent asthma in an older adult population is not well defined. This is due to the difficulties in separating the diagnosis of asthma from that of ...