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During the last decade, inhibitors of the vascular endothelial growth factor (VEGF) were developed for the treatment of cancer. Many anti-VEGF are available but the issue is still the same: to inhibit the effect of the VEGF on their receptors. There are two main classes, depending on the mechanism of action by blocking the binding of the ligand on the receptor (VEGF trap or monoclonal antibody) or by affecting directly the receptor (tyrosine kinase inhibitor [TKI], monoclonal antibody directed against the VEGF receptor). These selective agents are safe. Nevertheless, side effects were described, in particular renal and vascular effects. In this article, we analyze the frequency of these renovascular complications, their clinical aspects and the interest of these indexes as a marker of treatment efficacy.

Resume Introduction Les valeurs pronostiques de l’hypertension et de la proteinurie des anti-VEGF (facteur de croissance endothelial vasculaire) n’ont pas encore ete evaluees dans la pratique clinique de routine dans le cancer du sein (CS). Les objectifs de l’etude MARS etaient d’apprecier la prevalence/incidence de la proteinurie et de l’hypertension a l’inclusion et durant le traitement par anti-VEGF, et de rechercher un lien potentiel avec la survie globale. Methodes Les patients naifs de tout anti-VEGF et debutant un traitement par anti-VEGF ont ete inclus dans 8 centres entre 2009 et 2011 avec une periode de suivi de 1 an. Les resultats du groupe de patientes atteintes de CS et traitees par bevacizumab sont presentes. Resultats Quatre cent deux patientes atteintes de CS et traitees par bevacizumab ont ete incluses. A l’inclusion, 12,4 % des patientes presentaient une hypertension, 23,9 % une proteinurie. Lors du suivi, l’incidence d’evenements de novo , proteinurie et hypertension, etait respectivement de 61,7 % et 16,8 %. Parmi les patientes avec une proteinurie de novo , 62,2 % l’ont amelioree ou normalisee par la suite. Aucune microangiopathie thrombotique n’a ete rapportee. A l’inclusion ou de novo , les analyses univariees/multivariees ont demontre que la proteinurie et l’hypertension n’etaient pas associees a la survie globale. Discussion Ces resultats montrent que la prevalence de l’hypertension et de la proteinurie a l’inclusion etait elevee et que les patientes traitees par bevacizumab developpaient frequemment une hypertension et/ou une proteinurie de novo . Enfin, ni l’hypertension ni la proteinurie, a l’inclusion ou de novo , n’etaient associees a la survie globale dans notre cohorte.

Pain is frequent in cancer patients. To date, there is a consequent therapeutic arsenal so to manage pain; the different treatment strategies are the subject of various recommendations. Patients with cancer also frequently suffer from renal insufficiency, and this comorbidity may disrupt or jeopardize the analgesic strategy by changing the risk-benefit ratio of treatment options. This article provides recommendations for the use of drugs used for pain treatment after pointing out: 1) etiological and pathophysiological elements of pain; 2) therapeutic strategies for pain management; 3) data regarding renal failure in cancer and; 4) a point on drugs pharmacokinetics.

Resume Rationnel et objectif La prise en charge d’un cancer en cours de dialyse ou chez un transplante est complexe et pose la question des interactions entre maladie renale chronique et cancer. Materiel et methodes Nous avons cherche a preciser l’incidence des cancers dans la population des dialyses et des transplantes, leur profils et leurs causes a travers une revue de la litterature qui a ete realisee. Resultats Une importante prevalence de l’insuffisance renale a ete observee en cancerologie avec 60 % des patients presentant un debit de filtration glomerulaire anormale. Parallelement, l’incidence des cancers chez le patient dialyse apparait plus elevee que dans la population generale pour certains cancers. Ainsi, apres l’initiation de la dialyse, le risque de survenue d’un cancer et de l’ordre de 1,1 a 1,8 par rapport a la population generale. Chez le transplante renal, une augmentation de l’incidence de certains cancers de novo est egalement constatee avec un risque relatif de 2,5 a 3,9, selon le type de tumeur. Les causes sont multifactorielles (stress oxydant, traitements immunosuppresseurs, etc.) Conclusion Chez ces patients transplantes, le risque de cancer sous immunosuppresseur au long cours impose des precautions particulieres en termes d’indication de transplantation. Cela comporte une recherche d’antecedent de cancer chez le donneur, le receveur et un suivi oriente. Ainsi, les medecins sont confrontes a des decisions de don d’organe ou de greffe en prenant en compte le risque de cancer dans des populations a risque.

Resume Introduction L’augmentation croissante de l’incidence des cancers chez des patients en dialyse a ete etudiee depuis les annees 1970. Parallelement, l’emergence des therapies ciblees oblige les oncologues, nephrologues et les pharmaciens a s’interroger sur le maniement en dialyse de ces nouvelles classes de medicaments pour lesquels on dispose peu de donnees. Methode Cette revue de la litterature fait le point sur la pharmacocinetique, la tolerance et l’efficacite des principales therapies ciblees en France, les anticorps monoclonaux et les inhibiteurs de tyrosine kinase. Cette revue a ete realisee en utilisant sur Pubmed les mots cles : rein, dialyse, hemodialyse, insuffisance renale terminale ainsi que le nom de chaque medicament. Resultats De la meme facon que pour les medicaments cytotoxiques, il n’existe dans la litterature que des rapports de cas isoles ou des series de cas isoles. Il est cependant possible d’emettre quelques recommandations : il n’est pas necessaire de modifier la posologie des anticorps monoclonaux de par leur nature meme. En revanche, la pharmacocinetique des inhibiteurs de tyrosine kinase differe d’un medicament a l’autre et il n’est pas possible de faire de recommandations globales. Conclusion Le recours aux therapies ciblees est possible chez les patients dialyses. Cependant, plusieurs medicaments necessitent une attention particuliere en situation de dialyse. De plus, dans la mesure oU ces medicaments sont recents, il est important que les oncologues, nephrologues et les pharmaciens soient particulierement vigilants dans l’evolution de leurs pratiques d’utilisation. La publication de toute information d’utilisation dans cette situation doit etre encouragee.

The Renal Insufficiency and Anticancer Medications (IRMA) study is a French national, observational study, which demonstrated the high prevalence of abnormal renal function in a population of 4,684 solid tumour patients, treated in 15 cancer centers. Among them, 7.2% had a SCR level ≥ 110 mmol/L. In the 1,898 patients with breast cancer, only 31 patients (1.63%) had a SCR level ≥ 110 mmol/L. Nevertheless, respectively 51.8 and 50.8% had a creatinine clearance estimated with the Cockcroft-Gault and aMDRD formulae, below 90 mL/min. Even if the most used medications (anthracyclins, taxanes, trastuzumab, hormone therapies) are not nephrotoxic, these results are important because bevacizumab modifies the need for renal management. In case of renal insufficiency, some other treatments such biphosphonates IV, capecitabin and platin salts need drug dosage adjustment or interruption.

Anticancer drug management is complicated especially in renal insufficiency patients, a frequent situation in oncology. Several aspects need to be taken into account: first, the dosage. In this population, the kidney fails to eliminate drugs. Consequently, dosage adjustment can be necessary for drugs with pharmacokinetic profile altered by renal insufficiency in order to avoid dose-related side effects due to accumulation of the drug. Secondly, renal tolerance is an important aspect of anticancer drug management as renal insufficiency is a risk factor for developing renal side effects. Prevention of renal side effects is essential and means to limit this toxicity should be used, especially with hydration. Finally, it is essential to consider all the treatments prescribed in renal insufficiency patients in order to avoid accumulation of nephrotoxic drugs.

Resume L’utilisation des therapies ciblees est croissante dans le traitement du cancer. Les anticorps monoclonaux et les inhibiteurs de tyrosines kinases sont les plus couramment utilises, mais d’autres classes comme les inhibiteurs de mTOR sont egalement de plus en plus prescrits. Ces traitements sont volontiers donnes au long cours en phase metastatique et en traitement de maintenance. Il est donc important de surveiller l’occurrence de toxicites immediates, mais egalement de toxicites plus tardives et cumulatives. Les toxicites renales des therapies ciblees correspondent le plus souvent a des dommages structurels du nephron. Ainsi, les agents anti-epidermal growth factor receptor (EGFR) et anti-vascular endothelial growth factor receptor (VEGFR) ont des effets secondaires renaux car ces recepteurs de facteurs de croissance sont exprimes au niveau du rein. Les toxicites de molecules comme le bortezomib, l’erlotinib et le lapatinib sont moins connues. L’approbation par la US Food and Drugs Administration (FDA) et l’Agence europeenne du medicament (EMA) du sorafenib, du sunitinib et du temsirolimus a ete basee sur des etudes de moins 3 000 patients. Dans ce contexte, il y a assez peu de donnees sur leurs toxicites aigues et chroniques, notamment au niveau renal. Cette breve mise au point se propose de revenir sur les hypotheses physiopathogeniques, le diagnostic precoce et la prise en charge des toxicites renales des principales therapies ciblees disponibles en 2011.

Resume Introduction L’augmentation croissante de l’incidence des cancers en dialyse a ete etudiee depuis les annees 1970. Ainsi, les oncologues, les nephrologues et les pharmaciens sont de plus en plus confrontes a la problematique de l’utilisation des cytotoxiques chez les patients hemodialyses qui representent un million de patients a travers le monde et environ 36 000 patients en France. Chez les patients hemodialyses, les questions sont de deux ordres. D’une part, les patients hemodialyses n’ont plus de fonction renale fonctionnelle, exposant ainsi ces patients a un risque de surdosage et a des effets indesirables en cas de non-adaptation posologique. D’autre part, la possible dialysance des medicaments doit etre prise en compte afin de planifier au mieux l’administration des medicaments par rapport aux seances de dialyse et d’eviter une epuration trop precoce des medicaments par la dialyse et donc une inefficacite. Methode Cette revue de la litterature fait le point sur la pharmacocinetique, la tolerance et l’efficacite des traitements anticancereux chez le patient hemodialyse en utilisant sur Pubmed les mots cles : rein, dialyse, hemodialyse, insuffisance renale terminale ainsi que le nom de chaque medicament. Resultats Il n’existe sur ce sujet que des cas isoles ou de courtes series de cas dans la litterature. Une adaptation posologique en hemodialyse est necessaire pour 57,1 % des medicaments et 64,3 % doivent etre administres apres les seances de dialyse. Conclusion Les traitements anticancereux sont faisables en dialyse. Un grand nombre de medicaments necessitent une adaptation posologique et/ou une chronologie d’administration ajustee par rapport aux seances de dialyse tenant compte de leur dialysance. Des scores de fragilite, tels que ceux proposes en geriatrie, sont probablement necessaires pour guider la decision therapeutique.

A high prevalence of renal insufficiency has been observed in cancer patients as well as a high incidence of de novo cancer in dialysis or renal transplant patients.We aimed to determine the incidence of cancer in patients under dialysis and in kidney transplant recipients through a search of the literature.Under chronic dialysis, the risk of cancer increases from 1.1 to 1.8 in comparison to the general population. These risks reach 2.5 to 3.9 in renal transplant patients, but depend on the type of tumor.In transplant recipients, the risk of cancer induced by immunosuppressive therapy requires a specific follow-up and a screening for any medical history of cancer in the donor and the recipient.

The use of targeted therapies is increasing in the treatment of cancer. Monoclonal antibodies and tyrosine kinase inhibitors are the most commonly used but other classes such as mTOR inhibitors are increasingly prescribed. These treatments are often given in the long term in metastatic and maintenance treatments. It is therefore important to monitor the occurrence of immediate toxicities but also later and cumulative toxicities. Renal toxicities of targeted therapies are most often due to structural damages of the nephron. The anti-epidermal growth factor receptor (EGFR) and anti-vascular endothelial growth factor receptor (VEGFR) have renal side effects since growth factor receptors are expressed in the kidney. The toxicity of molecules such as bortezomib, erlotinib and lapatinib are less known. The approvals by the Food and Drugs Administration (FDA) and European Medicines Agency (EMA) of sorafenib, sunitinib and temsirolimus were based on studies of less than 3,000 patients. In this context, there is little data on their acute and chronic tolerance, including on the kidneys. This short review synthesizes the physiopathological hypotheses, early diagnosis and treatment of renal toxicity of major targeted therapies available in 2011.

The increased incidence of cancer in dialysis patients has been discussed since the mid 1970s. Furthermore, the emergence of targeted therapies (TT) requires oncologists, nephrologists and pharmacists to question themselves about the handling of these new classes of drugs in dialysis patients. While the cytotoxic drugs have been used in oncology for a long time, these new molecules are recent and clinical studies on their management in dialysis patients are missing.We reviewed the international literature on the pharmacokinetics, efficacy, tolerance and dosage adjustment of TT used in hemodialysis cancer patients, using the following keywords: kidney; renal; dialysis; hemodialysis; end-stage renal disease and the name of each drug.As described for cytotoxic drugs, there are only case reports or series published in the international literature. However, it is possible to propose some recommendations on TT handling in dialysis patients. It is not necessary to adapt the dose of monoclonal antibodies in dialysis patients. But it is important to considerer that this "class effect" is not true for all the other classes of drugs. In fact, the pharmacokinetic of tyrosine kinase inhibitors varies from drug to drug.The use of TT is possible in dialysis patients. However, many drugs require special attention in dialysis. In addition, because these drugs are new, it is important that oncologists, nephrologists, and pharmacists remain up to date about the management of TT in dialysis patients.

The increased incidence of cancer in dialysis patients has been discussed since the mid-70s. Consequently, oncologists, nephrologists and pharmacists are increasingly facing challenging situations of cytotoxic drug handling in dialysis patients. In dialysis patients, two main issues must be considered. First, renal function of hemodialysis (HD) patients is no longer functional. Therefore, these patients may necessitate drug dosage reduction, namely drug prescription, must be cautiously checked before administration with appropriate dosage adjustment whenever necessary to ensure efficacy while avoiding overdosage and related side effects. Secondly, drug clearance by dialysis must be taken into account for appropriate chemotherapy timing in order to avoid drug removal, which may result in a loss of efficacy.We reviewed the international literature on the pharmacokinetics, efficacy, tolerance and dosage adjustment of anticancer drugs used on hemodialysis cancer patients, using the key words: kidney, renal, dialysis, hemodialysis, end-stage renal disease and the name of each drug.Only case reports and small series were found. 57.1% of the drugs need dosage adjustment and 64.3% should be administered after the dialysis session.Cancer treatment in feasible in dialysis patients. Some drugs require dosage adaptation while others can be given as in patients with normal kidney function. These patients need coordinated care between oncologists, nephrologists and pharmacists to optimize drug delivery and logistics. Frailty scores, like in oncogeriatrics, should be built to optimally adapt cancer treatments in these dialysis patients.

Anticancer drug management is complicated especially in renal insufficiency patients, a frequent situation in oncology. Several aspects need to be taken into account: first, the dosage. In this population, the kidney fails to eliminate drugs. Consequently, dosage adjustment can be necessary for drugs with pharmacokinetic profile altered by renal insufficiency in order to avoid dose-related side effects due to accumulation of the drug. Secondly, renal tolerance is an important aspect of anticancer drug management as renal insufficiency is a risk factor for developing renal side effects. Prevention of renal side effects is essential and means to limit this toxicity should be used, especially with hydration. Finally, it is essential to consider all the treatments prescribed in renal insufficiency patients in order to avoid accumulation of nephrotoxic drugs.

The Renal Insufficiency and Anticancer Medications (IRMA) study is a French national, observational study, which demonstrated the high prevalence of abnormal renal function in a population of 4,684 solid tumour patients, treated in 15 cancer centers. Among them, 7.2% had a SCR level ≥ 110 mmol/L. In the 1,898 patients with breast cancer, only 31 patients (1.63%) had a SCR level ≥ 110 mmol/L. Nevertheless, respectively 51.8 and 50.8% had a creatinine clearance estimated with the Cockcroft-Gault and aMDRD formulae, below 90 mL/min. Even if the most used medications (anthracyclins, taxanes, trastuzumab, hormone therapies) are not nephrotoxic, these results are important because bevacizumab modifies the need for renal management. In case of renal insufficiency, some other treatments such biphosphonates IV, capecitabin and platin salts need drug dosage adjustment or interruption.

Antineoplastic drugs used in the treatment of cancers present with variable renal tolerance profiles. Among drugs with a potential for renal toxicity, platinum salts, methotrexate, and gemcitabine are well-known. The mechanisms of their renal toxicity and the means of its prevention are presented in this article. Anti-angiogenic drugs, recently marketed or still under clinical development, may also interact with the kidneys. In general, optimising the renal tolerance of anticancer drugs requires an appropriate evaluation of patients'renal function, before and during treatment, at each course. Serum creatinine alone is not a reliable index of renal function. Its evaluation must be performed with the use of Cockcroft-Gault or aMDRD formulae. In patients with abnormal renal function, dosage adjustment is often required to improve the renal tolerance, and also to limit the risk of extra-renal toxicities (such as haematological toxicities) induced by a drug overdosage, in those patients with reduced drug-elimination.