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Br J Cancer. 2012 Jan 31;106(3):468-74. doi: 10.1038/bjc.2011.555. Epub 2012 Jan 5.

Phase I study to assess the safety and tolerability of olaparib in combination with bevacizumab in patients with advanced solid tumours.

Author information

1
Clinical Trials Unit, Department of Medical Oncology, The Christie NHS Foundation Trust, The University of Manchester, Wilmslow Road, Manchester M20 4, BX, UK. emma.dean@christie.nhs.uk

Abstract

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.

PMID:
22223088
PMCID:
PMC3273358
DOI:
10.1038/bjc.2011.555
[Indexed for MEDLINE]
Free PMC Article

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