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International audience; Direct oral anticoagulants (DOAC) are now recommended for the treatment of cancer-associated thrombosis (CAT) based on the results of dedicated trials demonstrating that DOAC are non-inferior to low molecular weight heparins in preventing recurrent venous thromboembolism (VTE) in this population. The definition of "cancer patient" differs substantially among studies. Whether patients with active cancer and those with a history of cancer (HOC) carry the same risks of recurrent VTE and bleeding remains unclear. Few studies reported data on the efficacy and safety of anticoagulants according to active cancer or HOC categories. While in subgroup analyses of EINSTEIN and HOKUSAI the rates of recurrent VTE and bleeding did not differ between these categories, results from a subgroup analysis of AMPLIFY, from HOKUSAI-Cancer, and from the COMMAND cohort suggest that HOC patients might have a lower bleeding risk than active cancer patients. Whether the inclusion of HOC patients in CAT studies might introduce some bias by decreasing the rates of both recurrent VTE and bleeding remains an unanswered issue since no dedicated prospective study addressed this question. A strict definition of active cancer should be used in further trials.

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.

Background Data still remain scanty on the potential impact of chronic kidney disease (CKD) on the mortality of breast cancer (BC) patients. The results of 3 clinical studies we conducted (IRMA-2, CANDY and MARS) were pooled. In all 3, the methodology was the same regarding CKD, allowing pooled analysis on the prevalence of CKD and on the potential association between RI and overall survival (OS), and to stratify the risk, if any, depending on the GFR. Material and methods The KDIGO definition and classification of CKD was used. GFR was estimated with the MDRD formula. RI was defined as GFR Results The total population included 5908 solid cancer patients, among them, 1716 were young BC patients. Median age: 53.0 years, median body mass index: 23.4 kg/m2, bone metastasis: 27.7%, visceral metastasis: 38.7%. 75.9% of these patients were alive at the end of the 1-year follow-up. In these young BC patients, prevalences of a GFR Conclusion: This pooled analysis reported that: 1) abnormal GFR was frequent in young BC patients, 2) reduced GFR was a statistically significant prognostic factor for reduced OS. 3) This reduced OS began at an early stage of CKD in young BC patients, for a GFR Table. Multivariate Cox model regressions in BC patientsGFRn, %HR [95% CI]; p-value as compared to GFR ≥ 90GFR0.05GFR0.05GFR Citation Format: Launay-Vacher V, Janus N, Ray-Coquard I, Thariat J, Deray G, Beuzeboc P. Decreased overall survival in "young" breast cancer patients with renal insufficiency. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-08-33.

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.

BACKGROUND Vemurafenib is a BRAF inhibitor that has become the cornerstone of metastatic or inoperable melanoma therapy since its approval in 2011 in the United States and 2012 in Europe. This targeted therapy has shown impressive results in terms of increased progression-free and overall survival as compared to dacarbazine. The safety profile did not include any renal manifestations at that time. METHODS This report is the first case series of 8 patients who experienced significant to severe renal insufficiency under vemurafenib treatment. RESULTS This case series shows that vemurafenib may induce potentially severe acute renal failure, including renal sequelae and persistent kidney disease in some cases. CONCLUSIONS Further studies are needed to investigate the effects of vemurafenib on the kidneys. Meanwhile, renal function should be closely monitored in treated patients for early detection of any renal dysfunction occurrence. Cancer 2014;120:2158–2163. © 2014 American Cancer Society.

Background: Anti-VEGF drugs (AVD) are widely used in cancer patients (pts). Hypertension (HTN) and proteinuria (Pu) are class-side-effects of AVD, related to the inhibition of the VEGF pathway. The MARS study has been conducted to assess the renovascular tolerance of these drugs in the clinical setting. Methods: This multicentric, prospective, observational study evaluated the renovascular safety of AVD in pts naive from any AVD, conducted in 7 centres in France, from 2009 to 2012, with a follow-up (f/u) of 1 year. Data collected included: gender, age, serum creatinine (SCr), diabetes, HTN, hematuria (Hu) and dipstick Pu, at baseline and at each visit. Results: 1124 cancer pts were included; 402 breast cancer (BC) pts received bevacizumab (1st line: 14.4%; median durations of treatment: months)). Median age at inclusion was 55 years (19-65). Visceral, bone and cerebral metastasis frequencies were 74.7, 5.1 and 2.5%, respectively. HTN prevalences: 12.4%. Baseline renal assessment retrieved: Pu 23.9%, Hu 16.2%, mean aMDRD 96.4 ml/min/1.73m2 and 14 pts with aMDRD Conclusion: These results on the renovascular safety of bevacizumab in BC pts showed that 1) TMA is rare, 2) Grade 3 Pu developed in 4.6% of pts, with no grade 4, 3) less than 17% developed HTN, and 4) aMDRD was stable. Furthermore, in case of a renovascular effect, investigators followed the recommendations from the French Society of Nephrology (Halimi JM. Nephrol Ther 2008) and no treatment withdrawal for unmanageable renovascular toxicity occurred. Renovascular effects in MARS breast cancer patients treated with bevacizumabRenovascular effectsPrevalence at inclusionIncidence during follow-up (de novo**)Pu* (All grades)23.9%61.7%Pu* (Grade 1)22.2%47.1%Pu* (Grade 2)1.7%10.0%Pu* (Grade 3)0.0%4.6%Pu* (Grade 4)0.0%0.0%Hypertension12.4%16.8%Hu* (All Hu)16.2%42.1%Hu* (Traces/+)11.7%33.2%Hu* (++)2.6%6.3%Hu* (+++)1.9%2.6%SCr increase* (All grades)-80.0%SCr increase* (Grade 1)-68.6%SCr increase* (Grade 2)-7.1%SCr increase* (Grade 3)-0.3%*NCI-CTC v4; **de novo = patients with no event at inclusion and who presented an event during follow-up. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-15-06.

Background: Hypertension (HTN) and proteinuria (Pu) are class-side-effects of anti-VEGF drugs (AVD), related to the inhibition of the VEGF pathway. The MARS study has been conducted to assess the renovascular tolerance of these drugs in the clinical setting. Methods: The MARS study is a multicentric prospective observational study of the renovascular safety of AVD in AVD-naive patients. in 7 centres from 2009 to 2011. There was no intervention on the choice of the AVD. Data collected included: gender, age, serum creatinine (SCr), diabetes, HTN, hematuria (Hu) and dipstick Pu. This sub-group analysis presents the intermediate results for the first 184 patients with breast cancer (BC) receiving bevacizumab who completed the 1-year follow-up (f/u) (out of 337 BC patients in total). Results: All these 184 patients received bevacizumab (mean and median durations of treatment: 7.8 and 8 months, respectively). Median age at inclusion was 60 years. Bone, visceral and cerebral metastasis frequencies were 75.0, 52.2 and 7.1%, respectively. Diabetes and HTN prevalences were 4.3% and 10.3%, respectively. Baseline renal assessment retrieved: Pu 13.0%, Hu 8.2%, mean aMDRD 98.8 ml/min/1.73m2 and 1.1% had aMDRD Conclusion: These results show that 1) No thrombotic micro-angiopathy remains rare, 2) Pu developed in 16.3% of patients, with no grade 3/4, 3) less than 13% developed HTN, and 4) renal function was only slightly impaired with transient elevations in SCr. Furthermore, in case of a renovascular effect, investigators followed the recommendations from the French Society of Nephrology (Halimi JM et Al. Nephrol Ther 2008) and no treatment withdrawal for unmanageable renovascular toxicity occurred. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-17-04.

Renal insufficiency has been shown to be highly prevalent in patients with cancer. This renal insufficiency has been reported to be associated with reduced overall survival and increased cancer-related mortality. Therefore, it is important to screen patients with cancer for renal insufficiency, using an adequate and reliable method of estimation of the renal function. Renal insufficiency may influence 1 or several of the 4 pharmacokinetic phases (absorption, distribution, metabolism, elimination/excretion), potentially resulting in marked modifications of the pharmacokinetic profile of a drug in patients with renal insufficiency. Consequently, it is potentially necessary to adjust the dosage of anticancer drugs in case of renal insufficiency in order to avoid drug accumulation and in order to reduce overdosage-related side effects. This dosage adjustment of anticancer drugs should be performed according to the level of renal function and with an appropriate and validated method. It is not always easy to find clear information on anticancer drug handling in these patients. However, several guidelines, publications and handbooks are available on how to adjust anticancer drug dosages in patients with renal insufficiency and will help practitioners to manage anticancer drugs in such patients.

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.

Background: Half of anticancer drugs are predominantly excreted in urine. Dosage adjustment in renal insufficiency (RI) is, therefore, a crucial issue. Moreover, patients with abnormal renal function are at high risk for drug-induced nephrotoxicity. The Belgian Renal Insufficiency and Anticancer Medications (BIRMA) study investigated the prevalence of RI in cancer patients, and the profile/dosing of anticancer drugs prescribed. Methods:Primary end point: to estimate the prevalence of abnormal glomerular filtration rate (GFR; estimated with the abbreviated Modification of Diet in Renal Disease formula) and RI in cancer patient. Secondary end point: to describe the profile of anticancer drugs prescribed (dose reduction/nephrotoxicity). Data were collected for patients presenting at one of the seven Belgian BIRMA centres in March 2006. Results: A total of 1218 patients were included. The prevalence of elevated SCR (1.2 mg per 100 ml) was 14.9%, but 64.0% had a GFR90 ml min 1 per 1.73 m 2. In all, 78.6% of treated patients (n1087) were receiving at least one drug needing dosage adjustment and 78.1% received at least one nephrotoxic drug. In all, 56.5% of RI patients receiving chemotherapy requiring dose reduction in case of RI did not receive dose adjustment. Conclusions: The RI is highly frequent in cancer patients. In all, 80% of the patients receive potentially nephrotoxic drugs and/or for which dosage must be adjusted in RI. Oncologists should check the appropriate dose of chemotherapeutic drugs in relation to renal function before prescribing. © 2010 Cancer Research UK., SCOPUS: ar.j, info:eu-repo/semantics/published

International audience; 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. Among them, 50–60% had decreased renal function defined as CrCl below 90 and 80% were treated with anticancer drugs that either necessitated dosage adjustment in case of RI or were potentially nephrotoxic drugs. Since patients and drugs used differ depending on the type of tumour, the IRMA Study Group started analyses in different subgroups of patients. In the 1898 IRMA patients with breast cancer, the prevalence of RI was still very high in spite of a normal serum creatinine in almost all cases. Some anticancer drugs, as in particular some bisphosphonates, capecitabine and platinum salts, may be nephrotoxic and/or need dosage adjustment. However other important drugs in breast cancer do not require dose reduction, and do not present with potential nephrotoxicity (anthracyclines, taxanes, trastuzumab). Both issues seem to be slightly but significantly more important in patients with bone metastases as compared to patients with a non-metastatic disease.

Background The Renal Insufficiency and Cancer Medications (IRMA) study is a French national observational study. The results from this study of nearly 5,000 patients demonstrated the high prevalence of renal impairment in a population of patients with solid tumors. Methods Every cancer patient who presented at oncology departments that participated in the study over at least 1 of 2 predefined periods during 2004 were included. Renal function was calculated using Cockcroft-Gault and abbreviated Modification of Diet in Renal Disease (aMDRD) formulae to estimate the prevalence of renal insufficiency (RI) according to the Kidney Disease Outcomes Quality Initiative-Kidney Disease Improving Global Outcomes definition and stratification. Anticancer drugs were studied with regard to their potential renal toxicity and dosage adjustment. Results Of the 4,684 patients from the 15 centers, 7.2% had serum creatinine levels >110 micromol/L. However, when they were assessed using Cockcroft-Gault and aMDRD formulae, 57.4% and 52.9% of patients had abnormal renal function or RI, respectively. Of the 7,181 anticancer drug prescriptions, 53.4% required dose adjustments for RI. Of the patients treated, 79.9% received at least 1 such drug. And 80.1% received potentially nephrotoxic drugs. Conclusions RI was common in patients with cancer, and drug dosage adjustments often were necessary. Renal function should be evaluated in all cancer patients using either the Cockcroft-Gault formula or the aMDRD formula, including patients with normal serum creatinine levels. In patients who are at high risk for drug toxicity, the dosage should be adapted to renal function, and the use of nephrotoxic therapies should be avoided whenever possible.

180 Background: Anemia in cancer patients is common. The LIDOANEMIA-1 survey [Scotté F. MASCC 2015] reported that French clinicians do not follow EORTC guidelines. We aimed at improving EORTC guidelines dissemination among French physicians (FP). This second survey aimed at assessing the impact of our initiative on physicians’ behavior. Methods: Declarative survey conducted in France. The intervention consisted of having physicians watch a short video summarizing EORTC guidelines and their main messages for clinical practice. Evaluation of the impact of the intervention was performed with a 4-question web-based form FP filled in after seeing the video. Results: 319 FP answered the survey. Results are showed in the Table regarding the 4 main items: anemia diagnosis, Hb cut-off for considering RBC transfusion or ESA initiation, and Target Hb level on treatment. Among FP who were not following the guidelines, 67.7, 38.2, 50.8 and 65.2% declared they will follow them after the intervention, respectively for anemia diagnosis, Hb cut-off for considering RBC transfusion or ESA initiation, and Target Hb level on treatment. After the intervention, the expected proportion of FP who will follow EORTC guidelines is 93.2, 69.4, 82.6, and 89.4%, respectively for each item evaluated. Conclusions: Dissemination of guidelines is key to improve patient care. We tested a simple mean of presentation of EORTC guidelines in anemia management in cancer patients which significantly increased the proportion of FP who declare they will follow the guidelines. However, a non-negligible proportion of them does not agree and will not follow them, especially for the Hb cut-off for considering RBC transfusion. [Table: see text]

e16056 Background: MARS is a prospective multicentric study conducted to assess the renovascular tolerance of anti-VEGF drugs (AVD) in the clinical setting in France, in different tumor types. Meth...

1589 Background: Data still remain scanty on the potential impact of renal insufficiency (RI) on the mortality of cancer patients. The results of 3 clinical studies we conducted (IRMA-2, CANDY and ...

186 Background: MARS is a multicentric, non-interventional, prospective study which first reported the high prevalence of both baseline and de novo hypertension (HTN) and proteinuria (Pu) in several sub group of cancer patients [Gligorov J et al. SABCS 2013; Ray-Coquard I et al. ASCO GI 2014; Ray-Coquard I et al. ASCO GU 2014; Goldwasser F et al. ECC 2013; Launay-Vacher V et al. ASCO 2013]. In this sub-group analysis, we focused on elderly cancer (EC) patients treated by bevacizumab. Methods: MARS included 1,124 patients, all naïve of any previous anti-VEGF treatment. A First Renal Assessment was performed at baseline before the anti-VEGF was started with periodic follow-up for 1 year. Elderly was defined as age ≥65 years at inclusion. Univariate (UA) and multivariate analyses (MA) tested the associations of HTN and Pu, at baseline or de novo, with overall survival (OS) (pre-planned) in EC patients. Results: 845 patients treated with bevacizumab were included. Among them 226 were EC patients (colorectal 81, breast 78, ovarian 26, lung 22). At inclusion, HTA was statistically higher in EC patients (table), mean aMDRD was 79.6 ml/min/1.73m2 and 15.1% had aMDRD

2548 Background: MARS is a multicentric, noninterventional, prospective study which first reported the high prevalence of both baseline and de novo hypertension (HTN) and proteinuria (Pu) in patien...

394 Background: MARS is a prospective multicentric study conducted to assess the renovascular tolerance of anti-VEGF drugs (AVD) in the clinical setting in France, in a number of different tumor types. Methods: Patients (pts) from 8 centres were included when they were 1) naïve of any AVD and 2) about to start treatment with an AVD, from 2009 to 2012, with a follow-up (f/u) of 1 year. Data collected included: gender, age, serum creatinine (SCr), HTN, hematuria (Hu) and dipstick Pu, at baseline and at each visit during f/u. This sub-group analysis presents the results for renal cell carcinoma (RCC) pts receiving sunitinib. Results: 1,124 pts were included. 137 had RCC and 112 received sunitinib. Median age: 61.0 years. Visceral, bone and cerebral metastasis frequencies were 71.4, 42.0 and 12.5%, respectively. All except 3 pts, had at least one kind of metastasis. At inclusion, HTN prevalence was 43.8%. Baseline renal assessment retrieved: Pu 15.6%, Hu 8.1%, mean aMDRD 69.4 ml/min/1.73m2. The incidence of de novo Pu and HTN during f/u was 75.0 and 21.4% (Table). All pts with Pu at inclusion improved or remained stable. Among pts with de novo Pu, 75.8% afterwards improved/normalized. Mean aMDRD was 72.2 at the end of f/u. 0.7% had grade 3 SCr increase (no grade 4). No thrombotic micro-angiopathy (TMA) was reported. Conclusions: These results on the renovascular safety of AVD in RCC patients showed that 1) TMA is rare, 2) Pu develops in 75.0% of the pts, 3) 21.4% developed HTN, Furthermore, in case of a renovascular effect, investigators followed the recommendations from the French Society of Nephrology (Halimi JM. Nephrol Ther 2008) and no treatment withdrawal for unmanageable renovascular toxicity occurred. [Table: see text]

466 Background: MARS is a prospective multicentric study conducted to assess the renovascular tolerance of anti-VEGF drugs (AVD) in the clinical setting in France, in a number of different tumor types. Methods: Patients (pts) from 8 centers were included when they were 1) naive of any AVD and 2) about to start treatment with an AVD, from 2009 to 2012, with a follow-up (f/u) of 1 year. Data collected included: gender, age, serum creatinine (SCr), HTN, hematuria (Hu) and dipstick Pu, at baseline and at each visit during f/u. This subgroup analysis presents the results for colorectal cancer (CRC) pts receiving bevacizumab (BVZ). Results: 1,124 pts were included. 200 had CRC and all but 5 received BVZ. Median age: 63.2 years. Visceral, bone, and cerebral metastasis frequencies were 91.3, 10.8, and 0.5%, respectively. All pts presented metastasis. At inclusion, HTN prevalence was 26.2%. Baseline renal assessment retrieved: Pu 30.6%, Hu 10.1%, mean aMDRD 91.1 ml/min/1.73m2. The incidence of de novo Pu and HTN during f/u was 78.2 and 16.1% (Table). 75.6% of pts with Pu at inclusion improved or remained stable. Among pts with de novo Pu, 60.8% afterward improved/normalized. No grade 4 Pu has been reported (at inclusion or during f/u). Renal function decreased with a mean aMDRD of 90.3 at the end of f/u. 5.9% had grade 2 SCr increase (no grade 3-4). No thrombotic micro-angiopathy (TMA) was reported. Conclusions: These results on the renovascular safety of BVZ in CC patients showed that 1) TMA is rare, 2) Pu develops in 78.2% of the pts (no grade 4), 3) 16.1% developed HTN. Furthermore, in case of a renovascular effect, investigators followed the recommendations from the French Society of Nephrology (Halimi JM. Nephrol Ther 2008) and no treatment withdrawal for unmanageable renovascular toxicity occurred. [Table: see text]

e12504 Background: Anti-VEGF drugs (AVD) are widely used in cancer patients (pts). Hypertension (HTN) and proteinuria (Pu) are class-side-effects of AVD, related to the inhibition of the VEGF pathway. The MARS study has been conducted to assess the renovascular tolerance of these drugs in the clinical setting. Methods: This multicentric, prospective, observational study evaluated the renovascular safety of AVD in pts naive from any AVD, conducted in 7 centres in France, from 2009 to 2012, with a follow-up (f/u) of 1 year. Data collected included: gender, age, serum creatinine (SCr), diabetes, HTN, hematuria (Hu) and dipstick Pu, at baseline and at each visit. Results: 1,124 pts were included; 402 breast cancer (BC) pts received bevacizumab. Median age at inclusion was 55 years. Visceral, bone and cerebral metastasis frequencies were 74.7, 5.1 and 2.5%, respectively. HTN prevalences: 12.4%. Baseline renal assessment retrieved: Pu 23.9%, Hu 16.2%, mean aMDRD 96.4 ml/min/1.73m2 and 14 pts with aMDRD

5567 Background: Anti-VEGF drugs (AVD) are widely used in cancer patients (pts). Hypertension (HTN) and proteinuria (Pu) are class-side-effects of AVD, related to the inhibition of the VEGF pathway. The MARS study has been conducted to assess the renovascular tolerance of these drugs in the clinical setting. Methods: This multicentric, prospective, observational study evaluated the renovascular safety of AVD in pts naive from any AVD, conducted in 7 centres in France, from 2009 to 2012, with a follow-up (f/u) of 1 year. Data collected included: gender, age, serum creatinine (SCr), HTN, hematuria (Hu) and dipstick Pu, at baseline and at each visit. Results: 1,124 pts were included. 79 pts had ovarian cancer (OC) and all received bevacizumab. Median age at inclusion was 61 years. Visceral, bone and cerebral metastasis frequencies were 74.1, 52.7 and 6.0%, respectively. HTN prevalence was 16.5%. Baseline renal assessment retrieved: Pu 36.0%, Hu 21.3%, mean aMDRD 83.0 ml/min/1.73m2 and 5 pts with aMDRD

1095 Background: Hypertension (HTN) and proteinuria (Pu) are class-side-effects of anti-VEGF drugs (AVD), related to the inhibition of the VEGF pathway. The MARS study has been conducted to assess the renovascular tolerance of AVD in the clinical setting. Methods: The MARS study is a multicentric prospective observational study of the renovascular safety of AVD in AVD-naive pts. 7 centres from 2009 to 2011. Data collected included: gender, age, serum creatinine (SCr), diabetes, HTN, hematuria (Hu) and Pu. This sub-group analysis presents the intermediate results for the 1st 155 pts with breast cancer (BC) receiving bevacizumab who completed the 1-year follow-up (f/u) (out of 337 BC pts in total). Results: Median age at inclusion: 62 years. Bone, visceral and cerebral metastasis frequencies were 74.2, 51.6 and 5.2%, respectively. Diabetes and HTN prevalences were 3.9% and 10.3%, respectively. Baseline renal assessment retrieved: Pu 14.2%, Hu 8.4%, aMDRD 98.2 ml/min/1.73m2 and 2 pts with aMDRD2/year and 4 pts had aMDRD

e12005 Background: Anemia in cancer patients (pts) on dialysis may result from both chemotherapy-induced anemia and renal anemia. Survival on dialysis has improved during the past years and dialysi...

e13562 Background: 1 million people worldwide benefit from chronic dialysis with an increased rate in Western countries of 5% yearly. Significant improvements of chronic renal replacement therapy have led to prolonged survival. Due to mean age and heightened incidence of many cancers in dialyzed pts, the management of pts who suffer from both cancer and end-stage renal disease is challenging for oncologists and nephrologists. Specific questions were addressed to assess the efficacy/toxicity ratio, namely life expectancy, toxicity/dialysis clearance/optimal timing of chemotherapy. Methods: Retrospective multicentre review of dialysis centre charts for pts under dialysis who subsequently had a cancer. Results: Among 178 patients (66% male, median age 69) from 12 institutions, 35% were GU, 23% GI, lung 14%, hematologic 10%, head and neck 8%, or various others 10%. Most common histologies were adenocarcinomas 47%, of hematologic origin 17% and urothelial carcinomas 12%. Physical status was 0 48%, 1 18%, 2 30%...

BackgroundThe IRMA-1 study was the first to report on the high prevalence of renal insufficiency (RI) in 1898 breast cancer patients. The IRMA-2 study was started one year later, in another cohort of patients, and consisted of 2 phases: a cross-sectional study, similar to IRMA-1, and a 2-year retrospective follow-up of the patients to evaluate the impact of RI on survival. Data from the phase 1 of IRMA-2 were compared to the results of IRMA-1 in terms of RI prevalence and the potential association between RI and cancer survival was evaluated. We present here the results for IRMA-2 patients with breast cancer.Methods:The IRMA-1 and IRMA-2 studies included 4684 and 4945 patients, respectively, among which 1898 in IRMA-1 and 1816 in IRMA-2 had breast cancer (no dialysis). Sex, age, weight, serum creatinine (SCR), metastasis (bone and/or visceral), and anticancer drugs were collected. GFR was estimated with the aMDRD formula. RI was defined as aMDRD110µmol/l) was 2.0% (vs. 1.6% in IRMA-1), that of a GFR < 90 ml/min/1.73m² was 50.0% (vs. 50.8%) and that of a GFR < 60 ml/min/1.73m² was 7.7% (vs. 7.8%). No statistical different were found between the 2 populations.Among these 1816 patients, 1601 with available data (aMDRD and follow-up) were included in the survival analysis. RI at inclusion was strongly linked to mortality (Log Rank test, p=60, respectively, when analysing all patients.When the same analysis was performed for non-metastatic patients (n=918), by definition with a better prognosis, RI at inclusion was still associated with mortality (Log Rank test, p=0.01) with mean survivals of 21.2 and 22.9 months for patients with GFR=60, respectively.At inclusion, 81.2% of treated patients (n=1572) were receiving at least one drug needing dosage adjustment and 75.9% received at least one nephrotoxic drug (vs. 90.4 and 76.7%, respectively).Conclusion:The results of IRMA-2 and IRMA-1 confirm the high prevalence of RI in breast cancer patients, on 2 cohorts of nearly 2000 breast cancer patients each. Furthermore, patients with aMDRD Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2054.

9585 Background: Data are scant on the potential impact of renal insufficiency (RI) on the morbidity and mortality of cancer patients. The IRMA-2 study was started to evaluate the potential association between RI and cancer survival. Methods: Data were collected for cancer patients presenting at one of the 19 IRMA-2 centers in March 2005. Data included: sex, age, weight, serum creatinine, type of tumour, metastasis (bone and/or visceral). GFR was estimated with the abbreviated MDRD (aMDRD) formula at the inclusion. RI was defined as an aMDRD 2. Patients were retrospectively followed during 2 years after the inclusion. Survival analyses were performed with the log-rank test, survival median with the Mann-Whitney test, multivariate analysis with the Cox regression. Results: 4267 cancer patients (breast 1601, colorectal 575, lung 407, ovarian 269, prostate 224) with available data (aMDRD and follow-up) were included in the analysis. Median age 59.0, mean weight 66.2, 62.9% were women. 51.2% of these patients were alive at the end of the follow-up. RI was strongly linked to mortality (p [Table: see text] No significant financial relationships to disclose.

20627 Background: The most common side effect of Erlotinib (Erl) is skin toxicity. However, there is still no consensus on its management. The French PRECEDE study (PRise En Charge des Effets Demat...

16001 Background: Anti-VEGF drugs (AVD) are increasingly used and are associated with arterial hypertension (AH) and proteinuria. However, there are no data on the evolution of the glomerular filtr...

9121 Background: The IRMA study reported the high prevalence of renal insufficiency (RI) in 4684 solid tumour patients, with a glomerular filtration rate (GFR) 110 μmol/L was assessed. GFR was estimated with Cockcroft-Gault (CG) and abbreviated MDRD (aMDRD) formulae. Drugs necessitating dosage adjustment and those potentially nephrotoxic were identified. Chi-square test was used to compare the prevalence of RI between patients with BM and patients without, for all patients and for breast cancer (BC) ones. Results: 1,000 patients (BC 577) with BM were included: median age 60, mean 59.8, weight 66 kg, 659 women. The prevalence of SCR>110 μmol/L was 8.3%. That of GFR [Table: see text] No significant financial relationships to disclose.

9559 Background: The IRMA-1 study reported the high prevalence of renal insufficiency (RI) in 4,684 cancer patients, with a glomerular filtration rate (GFR) 2 for 52.9% and 12.0%, respectively. Furthermore, almost 80% of patients were receiving nephrotoxic drugs or drugs necessitating dosage adjustment. The IRMA-2 study was started one year later, in different patients, and consisted of 2 phases: 1) a cross-sectional study, similar to IRMA-1, and 2) a 2-year retrospective follow-up of the patients to describe the evolution of their renal function along with time. Data from the phase 1 were compared to the results of IRMA-1 in terms of RI prevalence. Methods: Data were collected for cancer patients presenting at one of the 19 IRMA-2 centers in March 2005: type of tumour, sex, age, weight, serum creatinine (SCR), and anticancer drugs. Dialysis, myeloma and lymphoma patients were not included. The prevalence of SCR>110 μmol/L was assessed. GFR was estimated with the aMDRD formula, anticancer drugs necessitating dosage adjustment and those potentially nephrotoxic were identified. Results: 4,945 patients (breast 1816, colorectal 747, lung 463, ovarian 294, prostate 251) were included in the IRMA-2 study. Median age 60.0, mean weight 66.2, 62.8% were women. The prevalence of an elevated SCR (SCR>110μmol/l) was 7.2% (vs. 7.2% in IRMA-1), that of a GFR < 90 ml/min/1.73m2 was 50.2% (vs. 52.9%) and that of a GFR < 60 ml/min/1.73m2 was 11.9% (vs. 12.0%) ( Table ). 73.2% of treated patients (n=3882) were receiving at least one drug needing dosage adjustment and 75.5% received at least one nephrotoxic drug (vs. 79.9 and 80.1%, respectively). Conclusions: The results of IRMA-2 and IRMA-1 confirm the high prevalence of RI in cancer patients, on 2 different cohorts of nearly 5,000 cancer patients each. This underlines that estimating renal function in cancer patients is mandatory and that this highly frequent co-morbidity should be considered. [Table: see text] No significant financial relationships to disclose.

e20574 Background: In 2007, the IRMA-1 study reported the high prevalence of renal insufficiency (RI) in cancer patients. Because of this high frequency, the IRMA-2 study started to investigate the evolution of renal function in cancer patients. Methods: Data were collected for cancer patients presenting at one of the 19 IRMA-2 centers in March 2005. Data included: sex, age, weight, serum creatinine (SCR), haemoglobinemia, type of tumour, metastasis (bone and/or visceral) anticancer drugs. Dialysis, myeloma and lymphoma patients were not included. Glomerular filtration rate was estimated with the abbreviated RD (aRD) formula at the inclusion. Patients were retrospectively followed during 2 years after the inclusion, every 6 months, from March 2005 (T0) to March 2007 (T24). Results: 4945 cancer patients (breast 1816, colorectal 747, lung 463, ovarian 294, prostate 251) were included in 19 cancer centre in France. Median age 60.0, mean weight 66.2, 62.8% were women. Mean GFR decreased from 90.8 ml/min/1.73m2 to 83.7 over the two years (table). Meanwhile, the prevalence of RI increased, reaching 62.9% and 17.5% for a GFR=90 at T0 had a GFR2 per year. This suggests that cancer patients are more exposed to a deterioration of renal function and that it should be closely monitored with at least a regular estimation of renal function, for instance every 6 months. So far, such a follow-up is not performed in clinical practice. Furthermore, drug therapy should be reevaluated, dosages adjusted when necessary, and some potentially nephrotoxic drugs changed for less or non-nephrotoxic drugs if possible. No significant financial relationships to disclose.

8603 Background: Patients with abnormal renal function are at high-risk for drug-induced nephrotoxicity. Furthermore, near half anticancer drugs are predominantly excreted in urine and dosage adjustment in RI is therefore a crucial issue. In 2005, the IRMA study (Insuffisance Rénale et Médicaments Anticancéreux) thus investigated the prevalence of RI in cancer patients and the profile of anticancer drugs prescribed. Methods: Data were collected for cancer patients presenting at one of the 14 IRMA centers in February 1st-15th or October 1st-15th, 2004: type of tumour, sex, age, weight, serum creatinine (SCR), haemoglobinemia, anticancer drugs. Dialysis and myeloma patients were not included. The prevalence of SCR>110 μmol/L was assessed. GFR was estimated with the Cockcroft-Gault (CG) and the abbreviated MDRD (aMDRD) formulae and patients were classified according to their K/DOQI stage of RI (Table). Anticancer drugs necessitating dosage adjustment and those potentially nephrotoxic were identified. Results: 4,684 patients (Breast, 1,898; Colorectal, 573; Lung, 445; Ovarian, 270; Prostate, 222) were included: mean age 58.1 years, weight 65.8 kg, sex-ratio 0.55. The prevalence of elevated SCR was 7.2% and those of GFR [Table: see text] No significant financial relationships to disclose.

20649 Background: Both anticancer drugs and kidney disease (KD) may induce anemia. In this analysis, we studied hemoglobin (Hb) levels of the pts in parallel with their renal function (RF) and thei...