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

Journal article

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.

Authors: Dean, E; Middleton, M; Pwint, T; Swaisland, H; Carmichael, J

• Publication status: Published
• Journal: British journal of cancer
• Volume: 106
• Issue: 3
• Pages: 468-474
• Publication date: 2012-01-05
• DOI: 10.1038/bjc.2011.555
• EISSN: 1532-1827
• ISSN: 0007-0920
• Language: English
• Keywords: Treatment Outcome; Infusions, Intravenous; Humans; Young Adult; Phthalazines; Poly(ADP-ribose) Polymerases; Breast Neoplasms; Receptors, Vascular Endothelial Growth Factor; Colorectal Neoplasms; Angiogenesis Inhibitors; Middle Aged; Adult; Male; Piperazines; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Antibodies, Monoclonal, Humanized; Administration, Oral