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Phase I trial of olaparib in combination with cisplatin for the treatment of patients with advanced breast, ovarian and other solid tumors.
- Source :
-
Annals of oncology : official journal of the European Society for Medical Oncology [Ann Oncol] 2014 Aug; Vol. 25 (8), pp. 1656-63. Date of Electronic Publication: 2014 May 14. - Publication Year :
- 2014
-
Abstract
- Background: To establish the maximum tolerated dose, determine safety/tolerability and evaluate the pharmacokinetics and preliminary efficacy of olaparib in combination with cisplatin in patients with advanced solid tumors.<br />Patients and Methods: Patients aged ≥ 18 years with advanced solid tumors, who had progressed on standard treatment, were assigned to a treatment cohort and received oral olaparib [50-200 mg twice daily (bid); 21-day cycle] continuously or intermittently (days 1-5 or 1-10) in combination with cisplatin (60-75 mg/m(2) intravenously) on day 1 of each cycle.<br />Results: Dose-limiting toxicities (DLTs) of grade 3 neutropenia (cisplatin 75 mg/m(2) with continuous olaparib 100 mg bid or 200 mg bid; n = 1 each) and grade 3 lipase elevation (cisplatin 75 mg/m(2) with olaparib 100 mg bid days 1-10 or 50 mg bid days 1-5; n = 1 each) were reported. Olaparib and cisplatin doses were subsequently reduced to 50 mg bid days 1-5 and 60 mg/m(2), respectively; no DLTs were reported for patients receiving this regimen. The most frequent grade ≥ 3 adverse events were neutropenia (16.7%), anemia (9.3%) and leucopenia (9.3%). Thirty patients (55.6%) received colony-stimulating factors for hematologic support. The overall objective response rate was 41% for patients with measurable disease, and 43% and 71% among patients with a BRCA1/2 mutation who had ovarian and breast cancer, respectively.<br />Conclusions: Olaparib in combination with cisplatin 75 mg/m(2) was not considered tolerable; intermittent olaparib (50 mg bid, days 1-5) with cisplatin 60 mg/m(2) improved tolerability. Promising antitumor activity in patients with germline BRCA1/2 mutations was observed and warrants further investigation.<br /> (© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Subjects :
- Adult
Aged
Breast Neoplasms pathology
Cisplatin adverse effects
Disease Progression
Female
Humans
Male
Middle Aged
Neoplasms pathology
Ovarian Neoplasms pathology
Phthalazines adverse effects
Piperazines adverse effects
Treatment Outcome
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Breast Neoplasms drug therapy
Cisplatin administration & dosage
Neoplasms drug therapy
Ovarian Neoplasms drug therapy
Phthalazines administration & dosage
Piperazines administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1569-8041
- Volume :
- 25
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Annals of oncology : official journal of the European Society for Medical Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 24827126
- Full Text :
- https://doi.org/10.1093/annonc/mdu187