Inequality factors in access to early-phase clinical trials in oncology in France: results of the EGALICAN-2 study.

BACKGROUND: Investigation of the disparities in the access to experimental treatment in early-phase clinical trials is lacking. The objective of the EGALICAN-2 study was to identify the factors underpinning such inequalities. METHODS: A national prospective survey was conducted in 11 early-phase clinical trial centers (CLIP2) certified by the French National Cancer Institute. Sociodemographic, socioeconomic and medical data were collected. Univariate logistic regression models were carried out to estimate odds ratios and 90% confidence intervals associated with the effect of each study variable. A multivariate logistic regression model was built to explore the independent factors associated with the administration of the experimental treatment (C1D1). A post hoc analysis was carried out excluding female cancer patients. RESULTS: Between 2015 and 2016, 1355 patients referred from 11 CLIP2 centers in France were included in the study. Eight hundred and forty-eight patients received C1D1 (73%) and 320 patients (27%) were screening failure. Median age was 58 years (range 17-97 years) and 667 patients (54%) were female. Most patients had a metastatic disease (n = 751, 87%). In the multivariate logistic regression analysis, the significant independent factors associated with C1D1 were male sex, initial care received in a hospital with an early-phase unit and living in wealthy metropolitan areas (P values <0.05). In the post hoc analysis, the sex factor was no longer significant [odds ratio = 1.21 (95% confidence interval 0.86-1.70), P value = 0.271]. CONCLUSIONS: This study investigated the factors producing social inequalities in the context of early-phase clinical trials in oncology. Our research highlights factors of sex, care pathway and geographic location. Gynecological cancer was found to impact C1D1 significantly, unlike breast cancer. The results of this study should contribute to improve patient access to early-phase clinical trials.

Effect of vitamin A deficiency on the in vitro transfer of mannose and N-acetylglucosamine in rat liver nuclei.

Liver nuclei, prepared from normal and vitamin A-deficient rats, were incubated in the presence of GDP-(14C)mannose or UDP-N-acetyl(14C)glucosamine and the labelled glycoproteins analysed by SDS PAGE. Fluorographic analysis has shown that (14C) mannose labelling is enhanced by vitamin A deficiency whereas N-acetyl(14C)glucosamine transfer remains approximately at the same level regardless of the vitamin A status; we did not notice any modification when the proteins were monitored by Coomassie blue or by silver nitrate.

Influence of vitamin A status and DDT on vitamin A-dependent protein mannosylation in rat liver.

Male Wistar rats of different vitamin A status (total depletion to moderate deficiency) were administered DDT (5 mg/kg/day) or vehicule (corn oil) i.p. daily for 14 days. Vitamin A-dependent protein mannosylation was measured either by in vivo incorporation of [3H]mannose into liver glycoprotein or by in vitro assay of incorporation of [14C]mannose into mannosylretinyl phosphate. Vitamin A deficiency resulted in a significantly impaired in vivo incorporation of mannose in liver glycoprotein but had no effect on the in vitro transport of mannose via retinyl phosphate. Although DDT induced an increase synthesis of liver proteins in smooth endoplasmic reticulum and caused a diminution of the hepatic vitamin A content, it did not affect vitamin A-dependent protein mannosylation.

Presence of a cellular retinylphosphate binding protein in rat liver.

A retinylphosphate binding activity, resolved during purification, has been discovered in rat liver cytosol. The partial purification includes ammonium sulfate precipitation and DEAE-cellulose chromatography. The macromolecular component responsible for the binding has a sedimentation coefficient of about 2 S and is sensitive to pronase. This binding is reversible and specific for retinylphosphate, since retinol, retinoic acid and retinoylphosphate do not compete with [3H]retinylphosphate.

Glycoprotein mannosylation in rat liver nuclei.

Nuclei and non-nuclear membranes were tested for their ability to transfer in vitro (14C)mannose from GDP-(14C)mannose to endogenous glycoprotein acceptors in the presence and in the absence of exogenous retinyl-phosphate. Electrophoretic analysis shows that retinylphosphate is responsible for the labeling of a few endogenous acceptors only in the non-nuclear membranes; in the nuclei the mannosylation reaction is not retinylphosphate dependent and the electrophoretic profile of the labeled protein acceptors is different from that of the non-nuclear membranes.

The phosphatidyl choline exchange properties in the cytosol of Aspergillus niger.

The presence of a PC-binding activity in the cytosol of Aspergillus niger van Tieghem has been established by measuring the reversible exchange of labeled DPC between an adsorbent (celite) and the cytosol. We have shown that this exchange is dependent upon the temperature and the ionic strength and it varies linearly with the protein concentration. This PC-binding activity is able to discriminate between DPC and some other phospholipids.

Spatial aspects of mannosyl phosphoryl retinol formation.

Rat liver microsomes catalyze the transfer of mannose from GDPmannose to both retinyl phosphate and dolichyl phosphate to form mannosylphosphorylretinol, mannosylphosphoryldolichol and GDP. The two reactions differ in term of reversibility. In fact, a 200-fold isotopic dilution of GDP[14C]mannose by unlabeled GDPmannose causes mannosylphosphoryldolichol labeling to disappear almost completely, while mannosylphosphorylretinol labeling remains at the same level. The same observation can be made if the mannose donor is removed by centrifugation and replaced by excess GDP; again mannosylphosphorylretinol is stable, but mannosylphosphoryldolichol drops down to one-third of its initial level, as expected for, respectively, a non-reversible and a reversible reaction. Placed in an aqueous medium, mannosylphosphorylretinol releases mannose 1-phosphate (beta configuration) whereas it is quite stable when kept in a membranous environment. These results strongly suggest that mannosylphosphorylretinol as soon as it is formed is segregated in such a way that it is no longer available to the back-reaction; the functional consequence of this segregation would be the possibility for mannosylphosphorylretinol to mannosylate some non-polar regions of certain protein chains.