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Primary tumor response to targeted agents in patients with metastatic renal cell carcinoma.

ABSTRACT: The recent development of multiple targeted agents for metastatic renal cell carcinoma (mRCC) has changed the treatment paradigm; hence the benefit and optimal timing of cytoreductive nephrectomy is being reevaluated.To determine primary tumor response to treatment with targeted agents in patients with mRCC.We reviewed the clinical and radiographic data of all mRCC patients seen at our institution between November 2004 and December 2009 without prior systemic treatment who received targeted therapy with their primary tumor in situ.Two independent reviewers measured the diameter of primary and metastatic tumors at baseline and subsequent scans, using Response Evaluation Criteria Solid Tumors (RECIST) v.1.1 to assess disease response.We identified 168 consecutive patients with a median 15 mo of follow-up and a median maximum tumor diameter of 9.6 cm. Median maximum primary tumor response was -7.1% (interquartile range: -14.0 to -0.1). A total of 61 patients had multiple studies available for evaluation. In 43 patients with <10% decrease in primary tumor within in the first 60 d, median maximum response was -7.2% at 154 d versus -24.5% maximum response at 174.5 d for 18 patients with ?10% decrease in primary tumor during the initial 60 d.Decrease in primary tumor diameter >30% while on targeted therapy for mRCC is rare, with most patients demonstrating minimal or no decrease in primary tumor diameter. Early response predicts a better overall primary tumor response.

SUBMITTER: Abel EJ

PROVIDER: S-EPMC4378833 | biostudies-other | 2011 Jan

REPOSITORIES: biostudies-other

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Primary tumor response to targeted agents in patients with metastatic renal cell carcinoma.

Abel E Jason EJ Culp Stephen H SH Tannir Nizar M NM Matin Surena F SF Tamboli Pheroze P Jonasch Eric E Wood Christopher G CG

European urology 20101016 1

<h4>Background</h4>The recent development of multiple targeted agents for metastatic renal cell carcinoma (mRCC) has changed the treatment paradigm; hence the benefit and optimal timing of cytoreductive nephrectomy is being reevaluated.<h4>Objective</h4>To determine primary tumor response to treatment with targeted agents in patients with mRCC.<h4>Design, setting, and participants</h4>We reviewed the clinical and radiographic data of all mRCC patients seen at our institution between November 200 ...[more]

PMID: 20952123

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Project description:BackgroundAlthough commonly observed, malnutrition is poorly characterized and frequently underdiagnosed in patients with metastatic renal cell carcinoma (RCC). The ability of nutritional screening tools to predict overall survival (OS) in patients with RCC has not been adequately validated. The objective of this study was to investigate the performance of nutritional screening tools and their additional prognostic value in patients with metastatic RCC treated with targeted therapies.MethodsPatients were prospectively recruited from three tertiary hospitals between 2009 and 2013. Nutritional status was evaluated using the Geriatric Nutritional Risk Index (GNRI) and the Mini Nutritional Assessment-Short Form (MNA-SF). Their OS and early grade 3/4 adverse events were recorded as outcomes of interest, and their associations with nutritional status were assessed using Cox regression and logistic regression, respectively. The incremental value in prognostication was evaluated using concordance index and decision curve analyses.ResultsOf the 300 enrolled patients, 95 (31.7%) and 64 (21.3%) were classified as being at risk of malnutrition according to the GNRI and MNA-SF, respectively. Both GNRI and MNA-SF were independent predictors of OS in multivariate analyses and provided significant added benefit to Heng risk classification. Compared with the MNA-SF, the GNRI contributed a higher increment to the concordance index (0.041 vs. 0.016). Nutritional screening, however, was not associated with early grade 3/4 adverse events in multivariate analyses. Further investigations are needed using more comprehensive and accurate assessment tools.ConclusionsThis prospective study confirmed the importance of nutritional screening tools in survival prognostication in patients with metastatic RCC. The standardized and objective measurements would allow clinicians to identify metastatic RCC patients at risk of poor survival outcomes. Individualized nutritional assessment and intervention strategies may be included in the multidisciplinary treatment.

Project description:BackgroundTargeted therapy (TT) in metastatic renal cell carcinoma (mRCC) may be associated with a high rate of toxicity that undermines treatment efficacy and patient quality of life. Polymorphisms in genes involved in the pharmacokinetic pathways of TTs may predict toxicity.ObjectiveTo investigate whether selected single-nucleotide polymorphisms (SNPs) in three core genes involved in the metabolism and transport of sunitinib and the mTOR inhibitors everolimus and temsirolimus are associated with adverse events (AEs).Design, setting, and participantsGermline DNA was extracted from blood or normal kidney tissue from mRCC patients of Caucasian ethnicity in two cohorts treated with either sunitinib (n=159) or mTOR inhibitors (n=62). Six SNPs in three candidate genes (CYP3A4: rs2242480, rs4646437, and rs2246709; CYP3A5: rs15524; and ABCB1: rs2032582 and rs1045642) were analyzed.Outcome measurements and statistical analysisPrimary endpoints were grade ≥3 AEs for all patients; grade ≥3 hypertension in the sunitinib cohort, and any grade pneumonitis in the mTOR inhibitors cohort. A logistic regression model was used to assess the association between SNPs and AEs, with adjustment for relevant clinical factors.Results and limitationsIn total, 221 samples were successfully genotyped for the selected SNPs. In the sunitinib cohort, the CYP3A4 rs464637 AG variant was associated with a lower risk of high-grade AEs (odds ratio 0.27, 95% confidence interval 0.08-0.88; p=0.03), but no SNPs were associated with hypertension. In the mTOR inhibitor cohort, none of the selected SNPs was associated with analyzed toxicities.ConclusionsWe observed an association between CYP3A4 polymorphisms and toxicity outcomes in mRCC patients treated with sunitinib, but not with everolimus or temsirolimus. Our findings are exploratory in nature, and further validation in independent and larger cohorts is needed.Patient summaryWe found that variants of CYP3A4, a gene involved in drug metabolism, are associated with sunitinib toxicity. This information may help in better selection of patients for targeted therapies in metastatic renal cell carcinoma.

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Primary tumor response to targeted agents in patients with metastatic renal cell carcinoma.

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Primary tumor response to targeted agents in patients with metastatic renal cell carcinoma.

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