Quality of life during first-line FOLFOX4±panitumumab in RAS wild-type metastatic colorectal carcinoma : results from a randomised controlled trial

Metastatic colorectal cancer is rarely curable. Improving quality of life is therefore a key treatment goal. We report quality of life for patients with RAS wild-type metastatic colorectal cancer in the PRIME study. A randomised phase 3 open-label study of first-line panitumumab+FOLFOX4 vs FOLFOX4 enrolled adults with untreated metastatic colorectal cancer and an Eastern Cooperative Oncology Group performance status of 0-2. This analysis includes patients with wild-type RAS tumours (n=505). Quality of life (prespecified end point) was assessed using the EuroQoL 5-domain health state index and overall health rating in all patients and by early tumour shrinkage status (≥30% reduction in size by week 8; exploratory end point). Differences in quality of life were assessed using analysis of covariance and a mixed-effect piecewise linear model, and were also analysed by skin toxicity severity. There were no statistically significant differences between treatment arms from baseline to progression or to discontinuation. Grade 3+ skin toxicity was reported by 38% of patients receiving panitumumab+FOLFOX4 and 2% receiving FOLFOX4 alone. There were no significant differences in quality of life between patients with grade 0-2 skin toxicity and those with grade 3+ skin toxicity. More patients receiving panitumumab+FOLFOX4 vs FOLFOX4 had early tumour shrinkage (p<.001). In patients with tumour symptoms at baseline, there were statistically significant improvements in quality of life in those with early tumour shrinkage versus those without early tumour shrinkage. Addition of panitumumab to FOLFOX4 in first-line therapy for metastatic colorectal cancer prolongs survival and has no negative effect on overall quality of life compared with FOLFOX4 alone. Specific quality of life assessments for skin toxicity should be included in study designs to better define the direct effect of these adverse events. NCT00364013

Prevention of Malaria in the Adult

peer reviewedGreat scourge of poor countries, malaria is the most important tropical parasitic disease. It is responsible for a large number of deaths in concerned countries and represents a real danger for travellers going to endemic regions. So, prophylactic measures are essential. On the one hand protective measures against mosquito bites, by wearing covering clothes, by using repellents and bed net (eventually impregnated with insecticide) will be useful. On the other hand, chemoprophylaxis is most often necessary, adapted to the possibility of chloroquine resistant P. falciparum, to the length or conditions of travel, and to the traveller's antecedents and age. Special concern about pregnant woman is necessary, due to potential severity of malaria. Chemoprophylaxis needs to be continued after coming back, for a duration depending on the drug used. Unfortunately, no prophylaxis is 100% effective, and the appearance of fever during the travel or two to three months after return requires medical advice. In some circumstances, it is necessary to prescribe a stand-by emergency treatment, if no quick medical advice is possible

Malaria: From Diagnosis to Curative Treatment

peer reviewedMalaria is a parasitic disease, with variable severity, provoked by the Plasmodium. It is present in tropical zones. The diagnosis is evoked by a fever occurring in a subject coming from a zone at risk, and is confirmed by microbiology. Considering the high prevalence of resistance to chloroquine, the treatment rests on quinine (or its derivatives) associated (or not) with an antibiotic. The severe forms of malaria, due to Plasmodium falciparum, are responsible for a high mortality rate. It requires urgent hospital management is required. Criteria defining this form deserve to be perfectly known

Prevention Strategies against Malaria

peer reviewedIn the absence of an efficacious vaccine, malaria prophylaxis remains important for the traveller in endemic areas. In addition to classical measures to protect against malaria vectors, chemoprophylaxis should be selected according to the geographic area. Besides a chemoprophylaxis scheme for the traveller, prevention modalities in pregnant women and in the general population living in an endemic area will also be briefly described

Pharma-Clinics. How I Treat ... Hiv Infection. III. Non-Nucleoside Reverse Transcriptase Inhibitors

peer reviewedNon nucleoside reverse transcriptase inhibitors (NNRTI) are a new arm in the treatment of the HIV infection. They inhibit the replication by direct non competitive binding to the enzyme, and do not require phosphorylation. The fast emergence of resistance in monotherapy obliges to use them in a triple association. The 103 mutation confers a cross-resistance. The most common adverse event is rash. Association with nucleoside analogues is additive or even synergistic. They are metabolized by the cytochrome P450. Within a combined therapy, their efficiency is comparable to protease inhibitors, notably in patients with low viral load

Pharma-Clinics How I Treat ... An Hiv Infection. Iv. Protease Inhibitors

peer reviewedProtease inhibitors constitute the last class of antiretroviral drugs appeared on the market. They raised an enormous enthusiasm, reinforced by recent studies results. These molecules prevent the formation of infectious viral particles, while inhibiting a viral enzyme that plays a key role in the cycle of replication of the HIV. Their efficiency, especially in association, is recognized for all stages of the infection and the intervening of a resistance often requires many mutations. However, the unexpected adverse events such as lipodystrophy and some interactions can limit their utilization in first intention

Le syndrome d'immunodéficience acquise : espoirs et limites thérapeutiques

Le SIDA reste une affection mortelle survenant dans certains groupes humains à haut risque qui sont actuellement bien connus. L'agent responsable pourrait être un rétrovirus. L'évolution se caractérise par des infections opportunistes graves (P. Carinii, T. Gondii, C. Neoformans) et/ou l'apparition d'un sarcome de Kaposi de haut degré de malignité. Au-del) du traitement des infections et du sarcome de Kaposi, la restauration de l'immunité cellulaire reste l'objectif prinicpal. Dans cette perspective, des essais sont actuellement en cours utilisant l'interféron, les hormones thymiques ou l'interleukine 2

Drug Clinics. How I Treat Hiv Infections. Ii. Nucleoside Reverse Transcriptase Inhibitors

peer reviewe

Epidemic Hantavirus Nephropathy

peer reviewedL'Entre-Sambre-et-Meuse a été le siège d'une épidémie de néphropathie épidémique à Hantavirus (NE) en 199293. Cinq cas ont été rencontrés au CHU de Liège en moins d'un an. Le virus responsable de cette affection appartient à la famille dès Hantavirus dont il existe huit sérotypes aux caractéristiques propres en terme de vecteur (rongeurs), de distribution géographique et de pathogénicité. Les pathologies induites chez l'homme vont de la néphropathie épidémique à Hantavirus - d'évolution le plus souvent bénigne- au syndrome pulmonaire à Hantavirus (SPH) - fréquemment mortel - en passant par la fièvre hémorragique avec syndrome rénal (FHSR) de sévérité intermédiaire. Dans nos contrées, on rencontre le sérotype Puumala dont le vecteur est le campagnol roussâtre. L'homme s'infecte par inhalation de particules contaminées et développe dans un pourcentage non précisé des cas, après une période d'incubation de 1 à 3 semaines, un tableau clinique de néphropathie épidémique à Hantavirus. Celui-ci se caractérise par l'apparition brutale d'une fièvre, de myalgies diffuses, de douleurs abdominales et/ou lombaires et de céphalées. Apparaissent ensuite à des degrés divers: nausées et vomissements, oligurie, myopie aiguë, toux,diathèse hémorragique, diarrhée... Biologiquement, on observe l'association d'une insuffisance rénale aiguë et d'une thrombopénie. L'évolution est spontanément favorable dans les deux à trois semaines. Le diagnostic suggéré par la clinique sera confirmé par la sérologie. La physiopathologie de l'insuffisance rénale et de la thrombopénie fait intervenir des interactions complexes entre l'hôte et le virus. Il n'existe pas de thérapeutique spécifique pour la néphropathie épidémique à Hantavirus. Les formes plus sévères (SPH et FHSR) peuvent bénéficierd'un traitement par Ribavirineen iv

Pathogenic Tracks in Fatigue Syndromes

This review analyses the recent literature devoted to two related fatigue syndromes: chronic fatigue syndrome (CFS) and acute onset postviral fatigue syndrome (PVFS). The articles are grouped into five pathogenic tracks: infectious agents, immune system, skeletic muscle, hypothalamo-pituitary-adrenal (HPA) axis and psychiatric factors. Although a particular infectious agent is unlikely to be responsible for all CFS cases, evidence is shown that host-parasite relationships are modified in a large proportion of patients with chronic fatigue. Antibody titres against infectious agents are often elevated and replication of several viruses could be increased. Chronic activation of the immune system is also observed and could be due to the reactivation of persistent or latent infectious agents such as herpes viruses (i.e. HHV-6) or enteroviruses. It could also be favorised by an impaired negative feedback of the HPA axis on the immune system. A model is proposed where the abnormalities of the HPA axis are primary events and are mainly responsible for a chronic activation of the immune system which in turn induces an increased replication of several viruses under the control of cellular transcription factors. These replicating viruses together with cytokines such as TNF-alpha would secondarily induce functional disorders of muscle and several aspects of asthenia itself