PMID- 22223088 OWN - NLM STAT- MEDLINE DCOM- 20120327 LR - 20231105 IS - 1532-1827 (Electronic) IS - 0007-0920 (Print) IS - 0007-0920 (Linking) VI - 106 IP - 3 DP - 2012 Jan 31 TI - Phase I study to assess the safety and tolerability of olaparib in combination with bevacizumab in patients with advanced solid tumours. PG - 468-74 LID - 10.1038/bjc.2011.555 [doi] AB - 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. FAU - Dean, E AU - Dean E AD - 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 FAU - Middleton, M R AU - Middleton MR FAU - Pwint, T AU - Pwint T FAU - Swaisland, H AU - Swaisland H FAU - Carmichael, J AU - Carmichael J FAU - Goodege-Kunwar, P AU - Goodege-Kunwar P FAU - Ranson, M AU - Ranson M LA - eng PT - Clinical Trial, Phase I PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20120105 PL - England TA - Br J Cancer JT - British journal of cancer JID - 0370635 RN - 0 (Angiogenesis Inhibitors) RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Phthalazines) RN - 0 (Piperazines) RN - 0 (Poly(ADP-ribose) Polymerase Inhibitors) RN - 2S9ZZM9Q9V (Bevacizumab) RN - EC 2.7.10.1 (Receptors, Vascular Endothelial Growth Factor) RN - WOH1JD9AR8 (olaparib) SB - IM MH - Administration, Oral MH - Adult MH - Aged MH - Angiogenesis Inhibitors/administration & dosage/pharmacokinetics MH - Antibodies, Monoclonal, Humanized/administration & dosage/*pharmacokinetics MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use MH - Bevacizumab MH - Breast Neoplasms/blood/drug therapy/metabolism MH - Colorectal Neoplasms/blood/drug therapy/metabolism MH - Female MH - Humans MH - Infusions, Intravenous MH - Male MH - Middle Aged MH - Phthalazines/administration & dosage/adverse effects/*pharmacokinetics MH - Piperazines/administration & dosage/adverse effects/*pharmacokinetics MH - *Poly(ADP-ribose) Polymerase Inhibitors MH - Receptors, Vascular Endothelial Growth Factor/*antagonists & inhibitors MH - Treatment Outcome MH - Young Adult PMC - PMC3273358 EDAT- 2012/01/10 06:00 MHDA- 2012/03/28 06:00 PMCR- 2013/01/31 CRDT- 2012/01/07 06:00 PHST- 2012/01/07 06:00 [entrez] PHST- 2012/01/10 06:00 [pubmed] PHST- 2012/03/28 06:00 [medline] PHST- 2013/01/31 00:00 [pmc-release] AID - bjc2011555 [pii] AID - 10.1038/bjc.2011.555 [doi] PST - ppublish SO - Br J Cancer. 2012 Jan 31;106(3):468-74. doi: 10.1038/bjc.2011.555. Epub 2012 Jan 5.