Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Background: This study evaluated safety, pharmacokinetics, and clinical activity of intravenous and oral rucaparib, a poly (ADP-ribose) polymerase inhibitor, combined with chemotherapy in patients with advanced solid tumours. Methods: Initially, patients received escalating doses of intravenous rucaparib combined with carboplatin, carboplatin/paclitaxel, cisplatin/pemetrexed, or epirubicin/cyclophosphamide. Subsequently, the study was amended to focus on oral rucaparib (once daily, days 1–14) combined with carboplatin (day 1) in 21-day cycles. Doselimiting toxicities (DLTs) were assessed in cycle 1 and safety in all cycles. Results: Eighty-five patients were enrolled (22 breast, 15 ovarian/peritoneal, 48 other primary cancers), with a median of three prior therapies (range, 1–7). Neutropenia (27.1%) and thrombocytopenia (18.8%) were the most common grade ≥3 toxicities across combinations and were DLTs with the oral rucaparib/carboplatin combination. Maximum tolerated dose for the combination was 240 mg per day oral rucaparib and carboplatin area under the curve 5 mg mL–1 min–1. Oral rucaparib demonstrated dose-proportional kinetics, a long half-life (≈17 hours) and good bioavailability (36%). Pharmacokinetics were unchanged by carboplatin coadministration. The rucaparib/carboplatin combination had radiologic antitumour activity, primarily in BRCA1- or BRCA2-mutated breast and ovarian/peritoneal cancers. Conclusions: Oral rucaparib can be safely combined with a clinically relevant dose of carboplatin in patients with advanced solid tumours. (Trial registration ID: NCT01009190)

Type

Journal article

Journal

British Journal of Cancer

Publisher

Cancer Research UK

Publication Date

25/01/2017

Keywords

rucaparib, carboplatin, PARP inhibitor, pharmacokinetics, pharmacodynamics, breast cancer, colorectal cancer, ovarian cancer, lung cancer;, pancreatic cancer, BRCA1, BRCA2