Audrey Thomas-Schoemann's research while affiliated with Paris Descartes University and other places

Publications (72)

Preprint
This case report describes of a pharmacokinetic drug–drug interaction between crizotinib, a tyrosine kinase inhibitor, and sofosbuvir/velpatasvir, a direct-acting antiviral drug, leading to cardiac toxicity. A 75-year-old man, with no cardiovascular history but a diagnosis of metastatic non-small cell lung cancer with MET exon-14 deletion and hepat...
Article
Full-text available
Background: Pazopanib (PAZ) is an oral angiogenesis inhibitor approved to treat soft tissue sarcoma (STS) but associated with a large interpatient pharmacokinetic (PK) variability and narrow therapeutic index. We aimed to define the specific threshold of PAZ trough concentration (Cmin) associated with better progression-free survival (PFS) in STS...
Preprint
Background. Pazopanib is an oral angiogenesis inhibitor approved to treat soft tissue sarcoma (STS) but associated with large interpatient pharmacokinetic (PK) variability and narrow therapeutic index. In order to improve its clinical use, this study aimed to define specific threshold of pazopanib trough concentration (Cmin) associated with better...
Article
Full-text available
Background The risk of drug–drug interactions (DDI) has become a major issue in cancer patients. However, data in sarcoma patients are scarce. We aimed to evaluate the frequency and the factors associated with DDI with antitumor treatments, and to evaluate the impact of a pharmacist evaluation before anticancer treatment.Patients and methodsWe perf...
Article
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Background. Pazopanib (PAZ) is an angiogenesis inhibitor approved for the treatment of renal cell carcinoma (RCC) and soft tissue sarcoma (STS). A relationship was reported between PAZ trough concentration (Cmin) and progression free survival (PFS) in RCC (Suttle A.B. 2015; Verheijen R.B. 2017). However, information on the exposure-efficacy relatio...
Preprint
Full-text available
Background: The risk of drug drug interactions (DDI) has become a major issue in cancer patient care. However, data in sarcoma patients are scarce. We aimed to evaluate the frequency of DDI with antitumor treatments, identify the risk factors for DDI and evaluate the impact of a pharmacist evaluation before anticancer treatment. Patients and Method...
Article
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The Coronavirus disease (COVID-19) pandemic is disrupting our health environment. As expected, studies highlighted the great susceptibility of cancer patients to COVID-19 and more severe complications, leading oncologists to deeply rethink patient cancer care. This review is dedicated to the optimization of care pathways and therapeutics in cancer...
Article
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A large interindividual variability has been observed in anti Programmed cell Death 1 (anti-PD1) therapies efficacy. The aim of this study is to assess the correlation of soluble PD-1 (sPD-1), soluble Programmed cell Death Ligand 1 (sPD-L1), Vascular Endothelial Growth Factor A (VEGFA), soluble CD40 ligand (sCD40L) and soluble CD44 (sCD44), with su...
Article
Background: The occurrence of severe, acute limiting toxicity in patients receiving anti-programmed cell death receptor-1 monoclonal antibodies, such as nivolumab, is largely unpredictable. Sarcopenia was found to be associated with anti-cytotoxic T-lymphocyte-associated protein 4 acute toxicity. We explore the clinical and pharmacological paramet...
Article
Purpose: Limited published data are available regarding the pharmacokinetic (PK) and pharmacodynamic (PD) variables of prolonged-release tacrolimus (PRT) after liver transplantations. The goal of this study was to compare the PK and PD profiles of PRT in early and stable liver transplant recipients by developing a population PK model of PRT and in...
Article
Aims: Cytidine deaminase (CDA) activity in cancer patients' serum has been proposed as a predictive biomarker for efficacy and toxicity of nucleoside analogues. However, discrepant results about its predictive value have been reported due to the high interindividual variability in CDA activity. This study aimed at identifying determinants of this...
Article
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Background The combination of mitotane and platinum-etoposide chemotherapy is a front-line treatment in metastatic adrenocortical carcinoma (ACC), although this regimen shows limited efficacy. Pharmacokinetic drug–drug interaction between mitotane, a strong CYP3A4 inducer, and etoposide, which is a substrate of CYP3A4, may contribute to chemoresist...
Article
Résumé Les thérapies ciblées orales sont une classe de médicaments anti-tumoraux en pleine expansion. À l’issue d’essais cliniques menés sur des populations sélectionnées, ces molécules sont approuvées le plus souvent selon une posologie unique. Pourtant, elles présentent une grande variabilité pharmacocinétique inter et intra-individuelle, et un i...
Article
Le corticosurrénalome est un cancer peu chimiosensible. L’association mitotane et chimiothérapie par platine-étoposide constitue le standard thérapeutique en première ligne métastatique. Le mitotane est un puissant inducteur du CYP3A4 de la BCRP et pourrait interagir avec l’étoposide (susbtrat du CYP3A4 et BCRP), et limiter son efficacité. Objecti...
Article
Dabrafenib is a potent and selective inhibitor of BRAF-mutant kinase that is approved, as monotherapy or in combination with trametinib (mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitor), for unresectable or metastatic BRAF-mutated melanoma, advanced non-small cell lung cancer and anaplastic thyroid cancer harbouring the BRAFV600E mut...
Article
The use of anticoagulants in patients with cancer is challenging as several co-morbidities modifying pharmacokinetic (PK) parameters and significant drug-drug interactions with concomitant anti-neoplastic therapies may lead to PK variability resulting in increased risk of thrombosis or bleeding. Data on the management of patients with cancer-associ...
Article
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Tyrosine kinase inhibitors (TKIs) used in the treatment of metastatic renal cell carcinoma present high interindividual variability in clinical response and toxicity. In addition, high interindividual variability in pharmacokinetics (PK) of TKIs is observed which could explain therapeutic failure or elevated toxicity in some patients. Monitoring of...
Article
Therapeutic drug monitoring (TDM) could be helpful in oral targeted therapies. Data are sparse to evaluate its impact on treatment management. This study aimed to determine a threshold value of plasma drug exposure associated with the occurrence of grade 3-4 toxicity, then the potential impact of TDM on clinical decision. Consecutive outpatients tr...
Article
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A disintegrin and metalloproteinase 9 (ADAM9) possesses potent metastasis-inducing capacities and is highly expressed in several cancer cells. Previous work has shown that ADAM9 participates in the adhesive-invasive phenotype in lung cancer cells in vitro. In this study, we evaluated whether ADAM9 expression plays a critical role in metastatic proc...
Article
Background: Circulating tumor DNA (ctDNA) has been reported as a prognostic marker in melanoma. In BRAF V600-mutant melanoma, a plasma under-exposure to vemurafenib could favor emerging resistance but no biological data are available to support this hypothesis. Objective: We aimed to investigate the relationship between vemurafenib plasma concen...
Article
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Background Older non-small cell lung cancer (NSCLC) patients under erlotinib are reported to experience more acute toxicity. We hypothesized that modifications in erlotinib pharmacokinetics might explain this observation. Methods A monocentric prospective clinico-pharmacological study included stage IIIb/IV NSCLC consecutive pts. treated with erlot...
Article
Purpose: Abiraterone acetate combined with prednisone improves survival in metastatic castration-resistant prostate cancer (mCRPC) patients. This oral anticancer agent may result in drug-drug interactions (DDI). We aimed to evaluate the prevalence of DDI with abiraterone and the possible determinants for the occurrence of these DDI. Methods: We...
Conference Paper
Background Cancer is becoming a chronic disease. Oncology patients have a higher risk of suffering medication related problems (MRPs) due to patient characteristics (ageing populations, polypharmacy and comorbidities) and the toxicity of cancer therapies. The presence of a clinical pharmacist in an oncology ward may be an effective intervention to...
Article
Nivolumab, an anti PD-1 monoclonal antibody, has been approved for the treatment of previously treated advanced or metastatic non-small-cell lung cancer (NSCLC). The aim of this study was to develop and validate an ELISA method for the quantification of nivolumab in plasma from patients with NSCLC in order to perform future pharmacokinetic/pharmaco...
Article
Introduction: In the past decade, treatment options for metastatic renal cell carcinoma and soft-tissue sarcoma have expanded. Pazopanib was discovered during the screening of compounds that suppressed vascular endothelial growth factor receptor-2 (VEGFR-2). As other tyrosine kinase inhibitors (TKI), pazopanib is not totally specific for one targe...
Article
Introduction: Sunitinib, a potent multi-tyrosine kinase (TK) inhibitor, is a standard first-line treatment for metastatic renal cell carcinoma (mRCC). In addition to its antiangiogenic activity, sunitinib is known to have immune-modulating properties especially on regulatory T-cells and tumor-infiltrating lymphocytes. However, data is sparse about...
Article
L’inhibition de la néoangiogenèse tumorale est un mécanisme d’action anti-tumoral qui est apparu majeur au cours de ces dernières années. Les inhibiteurs de tyrosine kinase incluant une action sur le récepteur du VEGF, tels que le sunitinib, le sorafénib, l’axitinib, le régorafénib, le pazopanib et le vandétanib permettent d’agir sur la croissance...
Article
Vemurafenib is a BRAF kinase inhibitor approved for first-line treatment of metastatic BRAF V600 -mutant melanoma. However, data on the pharmacokinetic/pharmacodynamic (PK/PD) relationship are lacking. The aim of this prospective, multicenter study was to explore the PK/PD relationship for vemurafenib in outpatients with advanced BRAF-mutated melan...
Article
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Background: Sunitinib is a protein tyrosine kinase (PTK) inhibitor that has immune-modulating properties. In this context, peripheral blood mononuclear cells (PBMC), mainly constituted by lymphocytes, could be a perfect surrogate tissue for identifying and assaying pharmacodynamic biomarkers of sunitinib. In this study, we investigated the changes...
Article
In a recent issue of the Journal of Clinical Pharmacology, we read with interest the paper by Thomeas et al [1] which evaluated the biological reproducibility and estimated relevant covariates for candidate circulating biomarkers of angiogenesis. The study examined VEGF-A, soluble VEGFR2 and angiopoietin 2 after exposure to sorafenib (Nexavar®, a p...
Article
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Introduction: UDP-glucuronosyltransferases (UGTs) are a multigenic family of enzymes responsible for the glucuronidation reaction. Many therapeutic classes of drugs used in solid tumors are UGT substrates, including cancer therapies. Areas covered: This article describes the tyrosine kinase inhibitors (TKIs) undergoing hepatic glucuronidation; i...
Article
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Introduction: The platelet-derived growth factor receptor (PDGFR) pathway has important functions in cell growth and, by overexpression or mutation, could also be a driver for tumor development. Moreover, PDGFR is expressed in a tumoral microenvironment and could promote tumorigenesis. With these biological considerations, the PDGFR pathway could...
Article
170 Background: Older age is a cause of disparity in cancer treatment decision and treatment guidelines for patients with comorbidities, polypharmacy, denutrition or psycho-social frailty are needed. A pre-therapeutic multidimensional assessment might improve the complex patient management. We developed an experimental program of integrated medicin...
Article
Introduction: Sunitinib is a multikinase inhibitor active in various cancers types including renal cancers and endocrine tumors. The study analyzed the influence of the lean body mass (LBM) and of pharmacogenetic variants on the exposure to sunitinib and its active metabolite, SU12662, and on sunitinib toxicity and clinical activity. Materials an...
Article
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A recent review showed frequent reductions of sorafenib dose in the treatment of metastatic thyroid cancer because of toxicity consistent with the findings of the phase III DECISION trial and contrasting with the safety of sorafenib in other cancer populations. The unexpected excess of toxicity observed in thyroid cancer patients may be linked to a...
Article
Introduction: Sorafenib is a multi-tyrosine kinase inhibitor (TKI). Considerable clinical experience has been accumulated since its first Phase III clinical trial in metastatic renal cancer patients in 2007. The management of its early acute toxicity in fit patients is well known. The management of prolonged treatment becomes the new challenge. A...
Article
The objective was to quantify the risk dynamics for the sorafenib-induced hand-foot syndrome (HFS) and to explore by simulations the dose-toxicity relationships according to different dosing regimens. Eighty-nine patients treated with sorafenib were considered: Treatment duration and regimen, and number and frequency of HFS observations were highly...
Article
Drug interactions are an on-going concern in the treatment of cancer, especially when targeted therapies, such as tyrosine kinase inhibitors (TKI) or mammalian target of rapamycin (mTOR) inhibitors, are being used. The emergence of elderly patients and/or patients with both cancer and other chronic co-morbidities leads to polypharmacy. Therefore, t...
Article
e15592 Background: Su (su), a tyrosine kinase VEGFR inhibitor, is subject to large inter-individual variability in drug exposure (AUC) and toxicity. We investigated the variability factors influencing AUC as well as the relationship between acute severe toxicity, AUC and genetic polymorphisms in adult cancer patients under su. Methods: The plasma c...
Article
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Vemurafenib and erlotinib are two oral kinase inhibitors approved for the treatment of metastatic melanoma and advanced non-small cell lung cancer, respectively. In contrast with erlotinib, the single published method for analysis of vemurafenib in human plasma is based on mass spectrometry. The purpose of the present study was to develop an HPLC-U...
Article
Full-text available
The depletion of regulatory T cells (Tregs) is a promising therapeutic strategy to enhance antitumor immune responses. Our recent findings indicate that low doses of arsenic trioxide can delay tumor growth in murine models of colon and breast cancer by depleting Tregs through oxidative and nitrosative bursts.
Article
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Immunotherapy is a promising antitumor strategy that can successfully be combined with current anticancer treatment. In this study, arsenic trioxide (As(2)O(3)) was shown to increase the antitumor immune response in CT26 colon tumor-bearing mice through the modulation of regulatory T cell (T(reg)) numbers. As(2)O(3) induced T(reg)-selective depleti...
Article
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Identifying predictive biomarkers of drug response is of key importance to improve therapy management and drug selection in cancer therapy. To date, the influence of drug exposure and pharmacogenetic variants on sorafenib-induced toxicity remains poorly documented. The aim of this pharmacokinetic/pharmacodynamic (PK/PD) study was to investigate the...
Article
The bystander effect (BE) is the ability of malignant cells affected by an anticancer agent to induce damage in neighboring cancer cells. In this study, we showed that it could also affect immune cells surrounding the tumor and interfere with the antitumor immune response. We observed that the exposure of human lung cancer cells A549 to vinorelbine...
Article
Full-text available
Oxidative stress plays a role in the regulation of cancer cell metastasis which involves cell invasion and adhesion that could be supported by ADAM proteins through the activities of their metalloprotease and disintegrin domains. We hypothesized that oxidative stress could act through the induction of ADAM9 protein in some cancer cells. Indeed, Wes...
Article
Sorafenib, an oral multitargeted tyrosine kinase inhibitor, is highly bound to plasma proteins (>99.5%). Little is known about the influence of variations in sorafenib protein binding on its disposition. The aims of this study were to characterize in vitro sorafenib binding properties to albumin using the quenching fluorescence method and investiga...
Article
Use of complementary and alternative medicine (CAM) has been reported to be more and more frequent among cancer patients in USA. The aim of this study was to analyze among French cancer patients the prevalence of CAM use, focusing on antioxidants (AO) that could interfere with antitumor agents. Seventy-nine patients, treated by antitumor chemothera...

Citations

... A recent observational study showed, in 70 STS patients, that pazopanib concentration was independently associated with the risk of toxicity and of progression at 3 months (OR 4.21, 95% CI (1.47-12.12), p = 0.008) [17]. ...
... In addition, studies have shown that patients with malignancies experience higher levels of distress, anxiety, and depression than general public. A longer course of treatment is also associated with greater anxiety (Pitman et al., 2018;Tsaras et al., 2018;Slimano et al., 2020), and depression have increased during the pandemic (Momenimovahed et al., 2021). Spiritual dryness also had a moderate negative correlation with the symptoms of depression, anxiety, and the perception of stress (Büssing et al., 2016). ...
... We showed that the exoPD-1 expression was significantly higher in the responding patients. Notably, this result was consistent with sPD-1 reported by a previous study in which an increase in sPD-1 concentration after two cycles of nivolumab, was associated with a longer overall survival (56). The most likely explanation for this could be that in responders, the ICIs might prevent the subsequent membrane PD-1/membrane PD-L1 interaction, thereby restoring tumor surveillance by enhancing T cell activity. ...
... In our statistical analysis, sarcopenia was not a significant factor for predicting irAEs, which was similar to our previous report (40) and other studies (16,18,27). However, previous study found that patients with sarcopenia experienced significantly increased risk of irAEs (22,41). It is generally believed that sarcopenia has been associated with a greater incidence of chemotherapy toxicity, but the impact of sarcopenia on irAEs remains controversial. ...
... significativamente reduzidos pelo uso de Adoport. Allard et al. (2019) Comparar os perfis de variáveis farmacocinéticas e farmacodinâmica do tacrolimus de liberação prolongada em receptores de transplante de fígado precoce e estável. ...
... Chez le sujet âgé, chez qui l'évaluation peut rapidement être complexe en cas de polypathologie, une réponse pour éviter un parcours chaotique peut être une médecine intégrée s'appuyant sur une pluridisciplinarité spécifique: le programme ARIANE développé à l'Hôpital Cochin en est déclinaison 7 possible. En un lieu unique, en hôpital de jour, le patient est évalué sur une journée par plusieurs spécialistes -gériatre, cardiologue, diabétologue, anesthésiste, pharmacien-qui convergent au lit du patient, lequel ne se déplace pas, permettant une synthèse immédiate, une réactivité des prises de décision, une cohérence entre les acteurs de soins et la prévention des décompensations organiques liés aux comorbidités (25). 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 ...
... If this can be verified by additional studies annoying and sometimes serious adverse dermatologic effects can be reduced or eliminated. Although Kramkimel et al. [8] suggests that there seems to be a correlation between clinical response to vemurafenib when used to treat high grade malignant melanoma, and severity of toxic rash, this observation was not noted in the large case series of 107 patients by Sinha et al. [4]. ...
... It leads to increased CDA gene transcription. As discussed in the previous section, CDA overexpression is associated with capecitabine toxicity because it is activated through CDA [206], as the deletion elevated CDA causes enhanced the risk of capecitabine-related hand-foot syndrome [207]. In addition, a retrospective analysis by Dahan et al. identified one more deletion rs532545 in the promoter region. ...
... Numerous studies have demonstrated that pharmacokinetic parameters, tissue distributions, and excretion could be altered by drug-drug, herb-drug or herb-herb interactions [8][9][26][27][28][29]. Therefore, the protective effect of A. officinarum on indomethacin-induced gastric injury might also be through the changes of pharmacokinetics for indomethacin and its metabolites to exert. ...
... In these patients, 24% of the time, a pharmacist suggested discontinuation, substitution, monitoring, or adjustments. Drug-drug interactions were more common in patients on tyrosine kinase inhibitors, and 29% of interactions were due to DS use [45]. ...