Trial reportInvestigational new drugs2013
Evaluation of the pharmacodynamics and pharmacokinetics of the PARP inhibitor olaparib: a phase I multicentre trial in patients scheduled for elective breast cancer surgery.
Trial report in Investigational new drugs, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
47 citing papers in PubMed, 88 citations in OpenAlex.
- Computational reactive-diffusive modeling for stratification and prognosis determination of patients with breast cancer receiving Olaparib.Scientific reports · 2023Trial
- Pharmacokinetic effects of proton pump inhibitors on the novel PARP inhibitor fluzoparib: a single-arm, fixed-sequence trial in male healthy volunteers.Investigational new drugs · 2021Trial
- PARP-1 inhibition attenuates tumor pathology in a novel murine model of diabetes-associated colitis-induced colorectal cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- PARP inhibitor olaparib induces DNA damage and acts as a drug sensitizer in an in vitro model of canine hematopoietic cancer.BMC veterinary research · 2025Article
- Subclonal response heterogeneity to define cancer organoid therapeutic sensitivity.Scientific reports · 2025Article
- Article
- Exposure-Response Analyses of Olaparib in Real-Life Patients with Ovarian Cancer.Pharmaceutical research · 2023Observational
- Androgen Deprivation Freezes Hormone-Sensitive Prostate Cancer Cells in a Reversible, Genetically Unstable Quasi-Apoptotic State, Bursting into Full Apoptosis upon Poly(ADP-ribose) Polymerase Inhibition.International journal of molecular sciences · 2023Article
- Pharmacokinetics and Pharmacodynamics of PARP Inhibitors in Oncology.Clinical pharmacokinetics · 2022Review
- PARP Inhibitors for Breast Cancer: GermlineCancers · 2022Review
- Counting the cost of public and philanthropic R&D funding: the case of olaparib.Journal of pharmaceutical policy and practice · 2022Article
- Glucose transporters: Important regulators of endometrial cancer therapy sensitivity.Frontiers in oncology · 2022Review
- GZ17-6.02 kills prostate cancer cellsFrontiers in oncology · 2022Article
- Carbon ion radiotherapy eradicates medulloblastomas with chromothripsis in an orthotopic Li-Fraumeni patient-derived mouse model.Neuro-oncology · 2021Article
- Pharmacokinetics, safety, and tolerability of olaparib and temozolomide for recurrent glioblastoma: results of the phase I OPARATIC trial.Neuro-oncology · 2020Article
- Therapeutic Approaches to Treat Mitochondrial Diseases: "One-Size-Fits-All" and "Precision Medicine" Strategies.Pharmaceutics · 2020Review
- Phase I dose-escalation and expansion study of PARP inhibitor, fluzoparib (SHR3162), in patients with advanced solid tumors.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2020Article
- Review
- Study protocols of three parallel phase 1 trials combining radical radiotherapy with the PARP inhibitor olaparib.BMC cancer · 2019Article
- Quantitative Characterization of Olaparib in Nanodelivery System and Target Cell Compartments by LC-MS/MS.Molecules (Basel, Switzerland) · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 8 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Olaparib (AZD2281) is an oral poly(ADP-ribose) polymerase (PARP) inhibitor with antitumour activity in cancer patients with BRCA1/2 germline mutations and in patients with homologous recombination deficiency. In this dose-finding study, patients were randomized to olaparib 10, 30, 100, 200 or 400 mg (capsule formulation) twice daily for the 4-5 days preceding breast cancer surgery. The primary objective was to identify an effective biological dose of olaparib for future trials. Secondary endpoints included evaluation of PARP-1 inhibition dose/exposure-response, and safety. Olaparib plasma pharmacokinetics (PK) and the pharmacodynamics (PD) in tumour and peripheral blood mononuclear cells (PBMCs) were evaluated. Population PK/PD modelling was performed on pooled data from this study and a previously reported study. Sixty patients were randomized (n = 12, each dose). Dose-dependent increases in exposure to olaparib were observed, but at ~50 % lower plasma exposure levels than seen in advanced disease studies. The mean maximal extent of PARP inhibition in PBMCs and tumour tissue was 50.6 % and 70.0 %, respectively, and was similar to inhibitory levels reported previously. No PARP inhibition-dose relationship was observed. Due to the unexpectedly low olaparib exposure, we were unable to determine an effective biological dose. Common adverse events included procedural pain (n = 31 patients), nausea, asthenia, malaise and increased blood creatinine (n = 6, each); these were of mild-to-moderate intensity, and all were manageable. Despite low olaparib exposure, PARP inhibition was consistent with previous reports. Reasons for the inter-study differences in exposure are unclear. The tolerability profile of olaparib was consistent with previous studies.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.