Nivolumab-induced pneumonitis and cardiopathy in a patient with relapsed Hodgkin's lymphoma.

Introduction: Nivolumab, the monoclonal antibody inhibitor of programmed cell death protein 1, enhances the T-cell response, including anti-tumour responses, by blocking the attachment of programmed death-ligand 1 and programmed death-ligand 2 ligands to the programmed cell death protein 1 receptor, which in turn leads to a reduction in tumour growth. Nivolumab has been approved in relapsed or refractory classic Hodgkin's lymphoma after autologous transplantation of haematopoietic stem cell and treatment with brentuximab as monotherapy.

Case Report: We herewith report a case of 65-year-old woman who developed an interstitial pneumonitis and a global cardiac hypokinesis following a treatment with Nivolumab for a refractory Hodgkin's Lymphoma.

Acute Kidney Injury Following High-Dose Methotrexate Administration in a Day Care Hospital.

Day care is a potential alternative to inpatient care of cancer patients. Using day care reduces medical costs substantially compared to inpatient care, which is driving the transfer of many inpatient chemotherapy protocols to day care hospitals (DCHs). However, in contrast to inpatient management, day care provides limited observation time, which could increase the risk of renal toxicity when using these protocols.

Human-cell-derived organoids as a new ex vivo model for drug assays in oncology.

In oncology, a 2D in vitro model of cancer cell lines is still widely used for large-scale drug screening. However, most promising candidates firstly identified by in vitro analysis tend to fail during the next steps of drug development. The generation of an ex vivo approach termed 'organoid' is emerging as a promising preclinical model to mimic human tumors more accurately.

Correlation between clinical response to sorafenib in hepatocellular carcinoma treatment and polymorphisms of P-glycoprotein (ABCB1) and of breast cancer resistance protein (ABCG2): monocentric study.

Objectives: We studied the relation between the polymorphism of P-glycoprotein (P-gp) and of breast cancer resistance protein (BCRP), encoded by ABCB1 and ABCG2 genes, respectively, and the pharmacokinetic variability and clinical response during the treatment with sorafenib of hepatocellular carcinoma.

Methods: At the Paul Brousse Hospital in Villejuif, France, 47 consecutive patients with advanced HCC treated with a single agent sorafenib, were enrolled. Sorafenib exposure was measured by its plasma concentration 3 h after oral administration of 400 mg (bid) by liquid chromatography.

Cetuximab directly inhibits P-glycoprotein function in vitro independently of EGFR binding.

Purpose: Cancer chemotherapy typically combines anticancer drugs from different mechanisms of action. However, cancer cells could become resistant to chemotherapy via P-gp or other ATP binding cassette proteins. The objective of this study was to evaluate whether cetuximab, monoclonal antibody directed toward epidermal growth factor receptor, could increase intracellular concentration of conventional chemotherapy by interacting with P-gp.

Therapy with boceprevir or telaprevir in HIV/hepatitis C virus co-infected patients to treat recurrence of hepatitis C virus infection after liver transplantation.

Objective: Severe hepatitis C virus (HCV) recurrence affects post-transplant survival in HIV/HCV co-infected patients. This article describes the results of triple anti-HCV therapy with boceprevir or telaprevir in seven HIV/HCV co-infected patients following liver transplantation.

Methods: All patients had severe HCV recurrence [fibrosis stage ≥F2 or acute hepatitis ≥A2 (n = 5) or fibrosing cholestatic hepatitis (n = 2)] associated with genotype 1a (n = 4) or 1b (n = 3).

Cetuximab increases concentrations of irinotecan and of its active metabolite SN-38 in plasma and tumour of human colorectal carcinoma-bearing mice.

In a previous study, we showed that cetuximab, a monoclonal antibody directed towards epidermal growth factor receptor, could inhibit P-glycoprotein (P-gp), an efflux protein of ATP-binding cassette family, and lead to an increased P-gp substrate intracellular concentration. Cetuximab is given with irinotecan to patients with metastasis colorectal cancer who did not respond to irinotecan-based therapy. The mechanism of this successful clinical reversion remains unknown.

Successful anti-hepatitis C virus therapy with telaprevir in an HIV/hepatitis C virus co-infected patient with a severe recurrence of hepatitis C virus infection on the liver graft.

We report, for the first time, the outcome of anti-hepatitis C virus (HCV) triple therapy with telaprevir in an HIV/HCV co-infected transplanted patient. After liver transplantation, the patient experienced a severe HCV recurrence with fibrosing cholestatic hepatitis, and anti-HCV therapy with pegylated interferon alpha 2a, ribavirin and telaprevir was initiated. A sustained virological response was achieved after 48 weeks of anti-HCV therapy.

Interferon-alpha improves docetaxel antitumoral and antimetastatic efficiency in Lewis lung carcinoma bearing mice.

Aims: Interferon-alpha (IFN-α) was shown to reduce P-glycoprotein (P-gp) expression and activity in several tissues. The purpose of this study was to evaluate the impact of IFN-α pretreatment on the antitumoral and antimetastatic, Docetaxel (DTX, P-gp substrate), on Lewis Lung Cancer (3LL) bearing mice and to correlate it to DTX pharmacokinetics.

Main Methods: Six groups of C57/Bl6 mice received subcutaneous (s.

Practical management of boceprevir and immunosuppressive therapy in liver transplant recipients with hepatitis C virus recurrence.

Hepatitis C virus (HCV) recurrence is the most important complication in HCV liver transplant patients. Boceprevir with pegylated interferon and ribavirin (PegIFN/RBV) enabled improvement in sustained virological response rates of patients with genotype 1 HCV. Boceprevir interacts with immunosuppressive therapy (IT) by inhibiting the cytochrome P450 3A enzyme.

Therapeutic efficiency of everolimus and lapatinib in xenograft model of human colorectal carcinoma with KRAS mutation.

KRAS mutation is a negative predictive prognostic factor during metastatic colorectal cancer treatment with antiepidermal growth factor receptor antibodies. For affected patients, new therapeutics must be explored. Our objective was to study efficacy of two drugs with different mechanisms of action, everolimus (mTOR inhibitor) and lapatinib (tyrosine kinase inhibitor), in a mouse xenograft model.

Generic drug prescriptions following hospital discharge: a prospective study in France.

Aims: Systematic generic prescription at discharge could reduce confusion on drug-name usage, decrease commercial influence on medicine, and reduce drug-related expenditures. This study aimed to analyze generic drug prescriptions at discharge from hospital and to estimate the potential savings associated with a total substitution policy (substitution of every substitutable drug for its cheapest generic counterpart).

Methods: Drug prescriptions before admission and at discharge of all patients from three medical units of a university hospital were prospectively collected for five weeks without informing prescribers.

Significance of isolated hepatic veno-occlusive disease/sinusoidal obstruction syndrome after liver transplantation.

After liver transplantation (LT), hepatic veno-occlusive disease (VOD), which is also known as sinusoidal obstruction syndrome (SOS), has been reported initially in relation to azathioprine use and subsequently in relation to acute rejection (AR). Isolated veno-occlusive disease (iVOD)/SOS raises some questions about its significance and especially its treatment. From the post-LT biopsy samples of 1364 patients (2000-2008), 31 patients with index biopsy samples showing VOD/SOS (2.

Cytotoxics compounded sterile preparation control by HPLC during a 16-month assessment in a French university hospital: importance of the mixing bags step.

The Centralized Chemotherapy Reconstitution Unit (CCRU) of Paul Brousse Hospital Pharmacy Department assessed the reliability of its Cytotoxics Compounded Sterile Products (CCSP) preparation method in order to improve its CCSP quality assurance system. Five cytotoxic drugs - gemcitabine, 5-fluorouracil, docetaxel, paclitaxel, and oxaliplatin - were assayed by high performance liquid chromatography (HPLC) to determine CCSP concentration. During the observation period, 23,892 CCSP were prepared.

Interleukin-2 treatment effect on imatinib pharmacokinetic, P-gp and BCRP expression in mice.

The aim of this study was to investigate the effect that recombinant interleukin-2 (rIL-2) (0.16 MUI/injection) had on the pharmacokinetics of imatinib (IM) in plasma. In this study, IM was given orally to mice at a dose of 150 mg/kg once a day for 11 days (from day 1 to 11) either alone or in combination with intraperitoneal injections of rIL-2 twice a day from day 8 to 11.

MDR1 polymorphism role in patients treated with cetuximab and irinotecan in irinotecan refractory colorectal cancer.

The aim of the study was to evaluate the influence of the MDR1 C3435T polymorphism on the therapeutic response in 23 patients treated with cetuximab plus irinotecan for irinotecan refractory liver metastatic colorectal cancer considering their KRAS status. Indeed, irinotecan and its active metabolite (SN-38) are both substrates of P-glycoprotein (P-gp) encoded by MDR1. Patients received cetuximab and irinotecan up to progression.

Enfuvirtide: a safe and effective antiretroviral agent for human immunodeficiency virus-infected patients shortly after liver transplantation.

The aim of this study was to evaluate the impact of an enfuvirtide-based antiretroviral (ARV) regimen on the management of immunosuppression and follow-up in hepatitis C virus (HCV)/hepatitis B virus (HBV)/human immunodeficiency virus (HIV)-coinfected liver transplant patients in comparison with a lopinavir/ritonavir-based ARV regimen. Tacrolimus and cyclosporine trough concentrations were determined at a steady state during 3 periods: after liver transplantation without ARV treatment (period 1), at the time of ARV reintroduction (period 2), and 2 to 3 months after liver transplantation (period 3). The findings for 22 HIV-coinfected patients were compared (18 with HCV and 4 with HBV); 11 patients were treated with enfuvirtide and were matched with 11 lopinavir/ritonavir-exposed patients.

Effect of the ABCB1 3435C>T polymorphism on tacrolimus concentrations and dosage requirements in liver transplant recipients.

Purpose: The effect of ABCB1 3435C>T on tacrolimus concentrations in liver transplant recipients was studied. Tacrolimus is a substrate for P-glycoprotein, the product of the ABCB1 gene. To determine whether the ABCB1 single-nucleotide polymorphism (SNP) 3435C>T was associated with variation in the tacrolimus concentration:dose ratio (C:D) in 42 liver transplant recipients during three months after transplantation.

Association between ABCB1 C3435T polymorphism and increased risk of cannabis dependence.

Prolonged cannabis use has a significant impact on health and well-being. Genetic factors are known to influence cannabis dependence, but few specific genetic markers have been identified. ABCB1 polymorphisms are known to modify drug pharmacokinetics but have yet to be studied for their role in generating and maintaining cannabis dependence.

Disposition of everolimus in mdr1a-/1b- mice and after a pre-treatment of lapatinib in Swiss mice.

The aim of this study was to document the in vivo transport of everolimus (inhibitor of mTOR) by P-glycoprotein (P-gp), and to investigate the influence of lapatinib (inhibitor of P-gp) on everolimus disposition. Pharmacokinetics of everolimus (0.25mg/kg) has been investigated after oral administration in mdr1a-/1b- mice compared to the wild type.

Effect of interleukin-2 pretreatment on paclitaxel absorption and tissue disposition after oral and intravenous administration in mice.

The aim of the present study was to investigate the effects of recombinant interleukin (rIL)-2 treatment on paclitaxel (PLX) pharmacokinetics in the plasma and tissue of Lewis lung carcinoma-bearing mice (lung tissues and s.c. tumors).

Disposition of Delta tetrahydrocannabinol in CF1 mice deficient in mdr1a P-glycoprotein.

P-glycoprotein (P-gp) plays a major role in drug efflux. All the transported substrates are more or less hydrophobic and amphiphatic in nature. Being lipophilic, Delta(9) tetrahydrocannabinol (THC), the main cannabis component, could be a potential P-gp substrate.

Effect of highly active antiretroviral therapy on tacrolimus pharmacokinetics in hepatitis C virus and HIV co-infected liver transplant recipients in the ANRS HC-08 study.

Objective: To characterise the interactions between tacrolimus and antiretroviral drug combinations in hepatitis C virus-HIV co-infected patients who had received a liver transplant.

Design: An observational, open-label, multiple-dose, two-period, one-sequence design clinical trial in which patients received tacrolimus as an immunosuppressive therapy during the postoperative period and then had an antiretroviral drug regimen added. Tacrolimus pharmacokinetics were evaluated at steady state during these two periods.

Tattooing breast cancers treated with neoadjuvant chemotherapy.

Background: In breast carcinomas treated with neoadjuvant chemotherapy, intraoperative identification of residual tumors may be difficult. A well-tolerated, low-diffusion charcoal suspension has been designed to tattoo breast tumors. In this study, we investigated whether this tattooing technique is efficient for localizing the tumor after treatment with chemotherapy.