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Clinical Trial
. 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

E Dean  1 , M R Middleton, T Pwint, H Swaisland, J Carmichael, P Goodege-Kunwar, M Ranson
Affiliations
Clinical Trial

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

E Dean et al. Br J Cancer. .

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.

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Figures

Figure 1
Figure 1
Disposition of all enrolled patients.
Figure 2
Figure 2
Geometric mean (±s.d.) plasma concentrations of (A) olaparib 200 mg b.i.d. and (B) olaparib 400 mg b.i.d. alone and in combination with bevacizumab (PK analysis set).
See this image and copyright information in PMC

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References

    1. Agency EM (2011) Avastin: European Public Assessment Report EMEA/H/C/000582-II/0040
    1. Aghajanian C, Finkler NJ, Rutherford T, Teneriello MG, Yi J, Parmar H, Nycum LR, Sovak MA (2011) OCEANS: a randomized, double-blinded, placebo-controlled phase III trial of chemotherapy with or without bevacizumab (BEV) in patients with platinum-sensitive recurrent epithelial ovarian (EOC), primary peritoneal (PPC), or fallopian tube cancer (FTC). J Clin Oncol 29(suppl): abst LBA5007 - PMC - PubMed
    1. Ashworth A (2008) A synthetic lethal therapeutic approach: poly(ADP) ribose polymerase inhibitors for the treatment of cancers deficient in DNA double-strand break repair. J Clin Oncol 26: 3785–3790 - PubMed
    1. Audeh MW, Carmichael J, Penson RT, Friedlander M, Powell B, Bell-McGuinn KM, Scott C, Weitzel JN, Oaknin A, Loman N, Lu K, Schmutzler RK, Matulonis U, Wickens M, Tutt A (2010) Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial. Lancet 376: 245–251 - PubMed
    1. Bergers G, Hanahan D (2008) Modes of resistance to anti-angiogenic therapy. Nat Rev Cancer 8: 592–603 - PMC - PubMed

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