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BACKGROUND: Olaparib (AZD2281) is a potent oral poly(ADP-ribose) polymerase inhibitor with anti-tumour activity and acceptable toxicity as monotherapy in patients with BRCA-deficient cancers. The vascular endothelial growth factor receptor inhibitor bevacizumab has been incorporated into standard of care with chemotherapy in various tumours. This phase I study established the safety, tolerability and clinical pharmacokinetics of olaparib alone and in combination with bevacizumab. METHODS: Patients with advanced solid tumours received increasing doses of continuous oral olaparib (100, 200 and 400 mg b.i.d. capsule formulation) in combination with bevacizumab (10 mg kg(-1) intravenous q2w). RESULTS: In all, 12 patients enrolled and received treatment. The most common adverse events (AEs) related to olaparib were grade 1/2 nausea and fatigue. No haematological parameters were reported as AEs. No serious AEs related to olaparib or dose-limiting toxicities (DLTs) were reported. Three patients discontinued due to AEs, two patients discontinued both olaparib and bevacizumab and one patient discontinued olaparib. Five patients received combination treatment for over 6 months. There was no evidence that bevacizumab affected olaparib. CONCLUSION: The combination of olaparib 400 mg b.i.d. with bevacizumab 10 mg kg(-1) q2w was generally well tolerated with no DLTs. This combination could be considered for future clinical investigation.

Original publication

DOI

10.1038/bjc.2011.555

Type

Journal article

Journal

Br J Cancer

Publication Date

31/01/2012

Volume

106

Pages

468 - 474

Keywords

Administration, Oral, Adult, Aged, Angiogenesis Inhibitors, Antibodies, Monoclonal, Humanized, Antineoplastic Combined Chemotherapy Protocols, Bevacizumab, Breast Neoplasms, Colorectal Neoplasms, Female, Humans, Infusions, Intravenous, Male, Middle Aged, Phthalazines, Piperazines, Poly(ADP-ribose) Polymerase Inhibitors, Receptors, Vascular Endothelial Growth Factor, Treatment Outcome, Young Adult