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Abstract Background Pazopanib is a multitarget tyrosine kinase inhibitor used in the treatment of renal cancer and soft tissue sarcoma. Its use is commonly associated with a number of side effects, such as hemorrhagic diathesis, neutropenia, leukopenia, thrombocytopenia, nausea, vomiting, abdominal pain, increased serum aspartate aminotransferase, increased serum alanine aminotransferase, decreased serum glucose, increased serum bilirubin, decreased serum phosphate and magnesium, fatigue, hypertension, diarrhea, anorexia, proteinuria, and hypothyroidism. Abscesses of metastases caused by pazopanib administration are rarely reported in the literature. Case presentation We report a case of abscesses of lung metastases related to pazopanib in a patient with metastatic renal cancer. The patient was a 53-year-old Caucasian man who developed abscesses of lung metastases during the first 3 months of treatment with pazopanib. The abscesses resolved after 1 month by stopping pazopanib and administering adequate antibiotic therapy. Conclusions We conclude that abscesses of metastases could be a rare side effect occurring during treatment with pazopanib in patients with renal cancer.

Introduction: In recent years, the systemic treatment of patients with metastatic renal-cell carcinoma (mRCC) has undergone profound innovations, offering the availability of new drugs, and raising the bar of the survival expectation in this, previously, almost-always, incurable disease. The likeliness of reaching durable response and long-term survival is still closely linked to good clinical management and smart treatment sequencing, rather than to a single systemic treatment choice. Areas covered: We review all systemic therapeutic options currently available, describe the evidence behind the current options available for mRCC patient treatment, and provide our personal cues to support clinical decisions. Expert opinion: The IMDC classification is still the only widely validated tool for the choice of primary therapy. Other elements should then be considered for selecting patients who can still receive TKI monotherapy (good-risk patients) or who deserve an 'all-at-once' approach with TKI plus ICI (poor-risk patients with the high metastatic burden and poor-prognosis organ involvement, likely not able to achieve a second chance), identifying these two 'extreme' situations and setting all the other treatment choices on the basis of several nuances. In the second- and further-line settings, ad-hoc prospective trials are awaited. [ABSTRACT FROM AUTHOR]

Background/Aims: As the most lethal urological cancers, renal cell carcinoma (RCC) comprises a heterogeneous group of cancer with diverse genetic and molecular alterations. There is an unmet clinical need to develop efficacious therapeutics for advanced, metastatic and/or relapsed RCC. Here, we investigate whether anthelmintic drug Niclosamide exhibits anticancer activity and synergizes with targeted therapy Sorafenib in suppressing RCC cell proliferation. Methods: Cell proliferation and migration were assessed by Crystal violet staining, WST-1 assay, cell wounding and cell cycle analysis. Gene expression was assessed by qPCR. In vivo anticancer activity was assessed in xenograft tumor model. Results: We find that Niclosamide effectively inhibits cell proliferation, cell migration and cell cycle progression, and induces apoptosis in human renal cancer cells. Mechanistically, Niclosamide inhibits the expression of C-MYC and E2F1 while inducing the expression of PTEN in RCC cells. Niclosamide is further shown to synergize with Sorafenib in suppressing RCC cell proliferation and survival. In the xenograft tumor model, Niclosamide is shown to effectively inhibit tumor growth and suppress RCC cell proliferation. Conclusions: Niclosamide may be repurposed as a potent anticancer agent, which can potentiate the anticancer activity of the other agents targeting different signaling pathways in the treatment of human RCC.

The authors report cases of metastatic renal cell carcinoma with level III-IV tumour thrombi in the inferior vena cava (IVC). Cases were treated with three courses of neoadjuvant sunitinib to reduce the thrombus level before surgery. Nephrectomy and tumour thrombectomy were performed, and sunitinib treatment continued after the operation. Cases 1 and 3 showed regression of lung metastases, but the size of the primary renal tumour and thrombus remained the same. The progression-free survival of the cases was 35 months and 24 months, respectively. In case 2, the primary renal tumour, metastases and thrombus showed regression. The upper limit of the thrombus decreased by 3 cm. In this case, the progression-free survival was 15 months, and the cancer-specific survival was 18 months. The neoadjuvant sunitinib treatment had a limited effect on downsizing the extent of tumour thrombi in the IVC. [ABSTRACT FROM AUTHOR]

Background: Pazopanib is a multitarget tyrosine kinase inhibitor used in the treatment of renal cancer and soft tissue sarcoma. Its use is commonly associated with a number of side effects, such as hemorrhagic diathesis, neutropenia, leukopenia, thrombocytopenia, nausea, vomiting, abdominal pain, increased serum aspartate aminotransferase, increased serum alanine aminotransferase, decreased serum glucose, increased serum bilirubin, decreased serum phosphate and magnesium, fatigue, hypertension, diarrhea, anorexia, proteinuria, and hypothyroidism. Abscesses of metastases caused by pazopanib administration are rarely reported in the literature.Case Presentation: We report a case of abscesses of lung metastases related to pazopanib in a patient with metastatic renal cancer. The patient was a 53-year-old Caucasian man who developed abscesses of lung metastases during the first 3 months of treatment with pazopanib. The abscesses resolved after 1 month by stopping pazopanib and administering adequate antibiotic therapy.Conclusions: We conclude that abscesses of metastases could be a rare side effect occurring during treatment with pazopanib in patients with renal cancer. [ABSTRACT FROM AUTHOR]

Introduction: Recent trials have emphasized the importance of a precise patient selection for cytoreductive nephrectomy (CN). In 2013, a nomogram was developed for pre- and postoperative prediction of the probability of death (PoD) after CN in patients with metastatic renal cell carcinoma. To date, the single-institutional nomogram which included mostly patients from the cytokine era has not been externally validated. Our objective is to validate the predictive model in contemporary patients in the targeted therapy era.Methods: Multi-institutional European and North American data from patients who underwent CN between 2006 and 2013 were used for external validation. Variables evaluated included preoperative serum albumin and lactate dehydrogenase levels, intraoperative blood transfusions (yes/no) and postoperative pathologic stage (primary tumour and nodes). In addition, patient characteristics and MSKCC risk factors were collected. Using the original calibration indices and quantiles of the distribution of predictions, Kaplan-Meier estimates and calibration plots of observed versus predicted PoD were calculated. For the preoperative model a decision curve analysis (DCA) was performed.Results: Of 1108 patients [median OS of 27 months (95% CI 24.6-29.4)], 536 and 469 patients had full data for the validation of the pre- and postoperative models, respectively. The AUC for the pre- and postoperative model was 0.68 (95% CI 0.62-0.74) and 0.73 (95% CI 0.68-0.78), respectively. In the DCA the preoperative model performs well within threshold survival probabilities of 20-50%. Most important limitation was the retrospective collection of this external validation dataset.Conclusions: In this external validation, the pre- and postoperative nomograms predicting PoD following CN were well calibrated. Although performance of the preoperative nomogram was lower than in the internal validation, it retains the ability to predict early death after CN. [ABSTRACT FROM AUTHOR]

Background/Aims: As the most lethal urological cancers, renal cell carcinoma (RCC) comprises a heterogeneous group of cancer with diverse genetic and molecular alterations. There is an unmet clinical need to develop efficacious therapeutics for advanced, metastatic and/or relapsed RCC. Here, we investigate whether anthelmintic drug Niclosamide exhibits anticancer activity and synergizes with targeted therapy Sorafenib in suppressing RCC cell proliferation. Methods: Cell proliferation and migration were assessed by Crystal violet staining, WST-1 assay, cell wounding and cell cycle analysis. Gene expression was assessed by qPCR. In vivo anticancer activity was assessed in xenograft tumor model. Results: We find that Niclosamide effectively inhibits cell proliferation, cell migration and cell cycle progression, and induces apoptosis in human renal cancer cells. Mechanistically, Niclosamide inhibits the expression of C-MYC and E2F1 while inducing the expression of PTEN in RCC cells. Niclosamide is further shown to synergize with Sorafenib in suppressing RCC cell proliferation and survival. In the xenograft tumor model, Niclosamide is shown to effectively inhibit tumor growth and suppress RCC cell proliferation. Conclusions: Niclosamide may be repurposed as a potent anticancer agent, which can potentiate the anticancer activity of the other agents targeting different signaling pathways in the treatment of human RCC. [ABSTRACT FROM AUTHOR]

Metastatic renal cell cancer is a malignant disease and its treatment has been not been described clearly yet. These patients are generally symptomatic and resistant to current treatment modalities. Radiotherapy, chemotherapy, and hormonal therapy are not curative in many of these patients. A multimodal approach consisting of cytoreductive nephrectomy, systemic therapy (immunotherapy or targeted molecules), and metastasectomy has been shown to be hopeful in prolonging the survival and improving the quality of life in some of these patients. Patients with oligometastatic disease and good performance status have better results following this multimodal approach. Cytoreductive nephrectomy and adjuvant/neoadjuvant systemic therapies (immunotherapy, targeted therapy) have been investigated for treatment options of metastatic renal cancer patients. After better understanding of the genetic basis and the molecular biology of the renal cell carcinoma, targeted molecular therapies and immunotherapies have emerged as more efficient alternative therapy options with moderate adverse effects. Metastasectomy in some of these patients improves survival and quality of life, especially in those with lung and bone metastases. In this review we will summarize treatment options for metastatic renal cancer patients. [ABSTRACT FROM AUTHOR]

Metastatic renal cell cancer (RCC) is a malignant disease without curative treatment. These patients are usually symptomatic and desperate for effective palliative treatment. Radiotherapy, chemotherapy, and hormonal therapy are not effective in these patients. A multimodal approach consisting of cytoreductive nephrectomy, systemic therapy (which includes cytokines or targeted molecules), and metastasectomy have been shown to be useful in prolonging the survival and improving the quality of life in a select group of patients with metastatic renal cancer. Patients with oligometastatic disease, good performance status, and delayed presentation of the secondaries have better results following this integrated approach. Although there is some controversy regarding the order in which nephrectomy and systemic therapy are to be instituted, well-controlled studies like the South West Oncology Group and European organization research and treatment of cancer have shown that upfront nephrectomy gives better survival compared to neoadjuvant systemic therapy followed by nephrectomy. This order is the standard presently. Of late, with better understanding of the genetic basis and the biology of the various subtypes of renal cell carcinoma, targeted molecular therapies have emerged as an equally effective alternative therapy to cytokines. Recent reports have proven that targeted therapy is more effective with comparable side effects. Metastasectomy in a subgroup of patients improves survival and quality of life specifically in those with lung secondaries and painful bone metastases.

Background: Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) are mainly known as anti-hypertensive drugs. Recent evidence suggests their anti-tumor potential against renal cancer. More than one-fourth of patients present with metastasis on their first visit., Objective: The purpose of the current study was to examine the potential clinical impact of ACEI/ARB on metastatic renal cell carcinoma (mRCC)., Methods: We searched through several online databases, including Pubmed, Scopus, Web of Science, and Embase, to find clinical studies that have investigated the association between treatment with ACEI/ARB and the survival of patients with mRCC. The hazard ratio (HR) and 95% confidence interval (95% CI) were utilized to assess the strength of the association., Results: A total of 6 studies with a total number of 2,364 patients were found eligible for the final analysis. The HR for the relationship between ACEI/ARB use and overall survival (OS) showed patients undergoing treatment with ACEI/ARB to have higher OS than non-users (HR: 0.664, 95% CI 0.577-0.764, p=0.000). Furthermore, the HR for the relationship between ACEI/ARB use and progression-free survival (PFS) showed patients undergoing treatment with ACEI/ARB to have higher PFS than non-users (HR: 0.734, 95% CI 0.695-0.794, p=0.000)., Conclusion: The results of this review offer ACEI/ARB as a potential therapeutic option associated with improved survival outcomes in patients receiving anti-vascular endothelial growth factor therapy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Treatment options and duration of therapy for patients with metastatic renal cell carcinoma (mRCC) have increased. Many patients now spend in excess of 2 years on active therapy. These patients’ needs, and the ability of health services to respond to them, are poorly understood. Ten patients living with mRCC for more than 2 years and treated with at least one targeted agent were selected at random from three hospitals in the United Kingdom (UK). One interviewer who was not involved in their care conducted in-depth interviews. Interview transcripts were analysed using Interpretative Phenomenological Analysis (IPA) to identify issues of greatest importance to patients, and to understand how well patients felt their needs were being addressed. Perceived delay in initial diagnosis was a major theme. Being told the truth about treatment side effects upfront was important, but was often at odds with perceived delivery. ‘Dealing with side effects’, understanding dose and its effects and not letting ‘negative thoughts get in’ were highlighted as important, but were highly personal to patients and areas where patients struggled. Concordance was observed with delivery of ‘a clear next step’ for treatment, timely access to drugs and guidance on a drug ‘holiday’. Patient experience of mRCC and its treatment requires a tailored approach. This research suggests there are key opportunities for service improvement and improved communication throughout the pathway to better meet the needs of patients, including non-clinical support to build personal resilience.

Abstract We present an unusual case of a metastatic renal cell carcinoma (RCC) mimicking trigeminal schwannoma. The patient, with no prior history of RCC, presented with clinical symptoms and imaging consistent with trigeminal neuralgia secondary to trigeminal schwannoma. Magnetic resonance imaging of the brain showed a large bilobed cystic/solid mass primarily in the cerebellopontine angle cistern, with extension into the left middle cranial fossa, Meckel cave, and left cavernous sinus. Following surgical excision, histopathology revealed the tumor to be an RCC infiltrating into the trigeminal nerve fascicles. Further imaging and investigation revealed widespread metastasis to the vertebral bodies and long bones. Metastatic RCC to the trigeminal nerve is rare. Despite the development of more effective treatment modalities, the prognosis of metastatic RCC remains poor. To our knowledge, this is the first reported case of RCC metastasizing to the trigeminal nerve fascicles.

Pazopanib and sunitinib are treatment options for metastatic renal cell cancer (mRCC), with similar efficacy, and minor differences in their toxicity profile. Our experience has suggested that pazopanib-induced alopecia may be a potentially significant but previously under-reported toxicity. For this reason we performed a retrospective review of the clinical records of all patients with mRCC treated with pazopanib at the Royal Marsden Hospital from European licensing until June 2013, and all patients treated with sunitinib over the same period. We found that 36 patients with mRCC were treated with pazopanib and 85 patients with sunitinib. Four of the 36 (11%) patients treated with pazopanib developed alopecia severe enough to warrant a wig, versus none of 85 patients treated with sunitinib (p = 0.007). In conclusion, grade 2 pazopanib-induced alopecia was reported at significantly higher rates when compared to sunitinib-induced alopecia. Hence, in our view, patients should be informed about this potential toxicity when discussing the treatment options for metastatic renal cell cancer.

Sunitinib, a multitargeted tyrosine kinase inhibitor, is the frontline therapy for renal and gastrointestinal cancers. In view of its well-documented proapoptotic and immunoadjuvant properties, we speculate that combination of Sunitinib and immunotherapy would provide a synergistic antitumor effect. Here, we report that a remarkably synergistic antitumor responses elicited by the combined treatment of Sunitinib and an agonistic antibody against glucocorticoid-induced TNFR related protein (GITR) in a model of metastatic renal cell carcinoma. Sunitinib significantly increased the infiltration, activation, and proliferation and/or cytotoxicity of CD8+ T cells and NK cells in liver metastatic foci when combined with the anti (α)-GITR agonist, which was associated with treatment-induced prominent upregulation of Th1-biased immune genes in the livers from mice receiving combined therapy versus single treatment. Sunitinib/a-GITR treatment also markedly promoted the maturation, activation and cytokine production of liver-resident macrophages and DCs compared with that achieved by α-GITR or Sunitinib treatment alone in mice. Cell depletion experiments demonstrated that CD8+ T cells, NK cells and macrophage infiltrating liver metastatic foci all contribute to the antitumor effect induced by combined treatment. Furthermore, mechanistic investigation revealed that Sunitinib treatment reprograms tumor-associated macrophages toward classically activated or "M1" polarization upon GITR stimulation and consequently mounts an antitumor CD8+ T and NK cell response via inhibiting STAT3 activity. Thus, our findings provide a proof of concept that Sunitinib can synergize with α-GITR treatment to remodel the tumor immune microenvironment to trigger regressions of an established metastatic cancer. [ABSTRACT FROM AUTHOR]

The superior vena cava syndrome is an oncological emergency that requires an accurate and quick diagnosis. The most scenarios, the primary tumor is unkown. The obstruction can be secondary to solid tumor in 5% of the cases. A classical presentation is facial or cervical edema, cough, dyspnea, headache and thoracic pain. The clinical repercussion will depend on the it's speed of establishment. The prognosis will depend on its ethiology. Clinical case: A 56 year old male with a rapidly progressive volume of the left supraclavicular region with a 20 kg loss in two months. Biopsy showed a metastatic non differentiated tumor. A CT showed a mass of 122 x 73 x 77 mm with vascular structure displacement. Renal tumor of 124 x 129 x 190 mm which extends to the perirrenal fat and vena cava. Biopsy showed a clear cell carcinoma, Fuhrman 2. Renal clear cell carcinoma will only arise as supraclavicular methastasis in 10% and with superior vena cava syndrome in less than 1% of the cases, both with a rapid progression and death. [ABSTRACT FROM AUTHOR]

Background: Management and palliation of pathologic fracture (PFx) secondary to metastatic prostate (mCaP) and renal cancer (mRCa) is hospital resource intensive. Using a national all-payer database, we assessed the burden of PFx secondary to mCaP and mRCa nationwide. Admission rates, mortality, surgical fixation rates, and risk factors for high-cost admissions for pathologic fractures were assessed METHODS: National Inpatient Sample was queried from 2013 to 2015 for mCaP and mRCa admissions. Hospitalization costs of PFx was assessed over time by cancer type. Hospitalization outcomes were stratified by cancer type. Multivariable logistic regression models were constructed to examine predictors of high-cost admission for PFx (>75th percentile).Results: From 2013 to 2015, there were 21,466 and 6,334 admissions for mCaP and mRCa with bone metastasis, respectively. Proportion of admissions for PFx was greater in mRCa than mCaP (15.9% vs. 7.2%, P < 0.01). PFx secondary to mRCa was associated with longer length of stay, hospitalization cost, and greater rate of surgical fixation. Costs of admission for PFx increased by $4,005 dollars from 2013 to 2015 for mRCa (P = 0.03), but did not increase for mCaP (P = 0.5). On multivariable analysis, mRCa was associated with greater odds of PFx (OR:2.12, P < 0.01), and high-cost hospitalization for mRCa associated PFx (OR:1.37, P = 0.02).Conclusions: PFx secondary to mRCa represents a significant health care burden. mRCa was associated with greater odds of PFx compared to mCaP, as well as greater inpatient morbidity and cost. Formalized guidelines on screening and management of bone lesions in mRCa may be needed to mitigate this under-recognized health care burden. [ABSTRACT FROM AUTHOR]

Objective. The aim of this study was to evaluate overall survival (OS) after treatment of metastatic renal cell carcinoma (mRCC) following the introduction of tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin (mTOR) inhibitors. Material and methods. One-hundred and forty-three consecutive mRCC patients were given immunotherapy ( n = 59), TKIs ( n = 49) or sequential therapy (IMM→TKI group; n = 35). The TKI group included patients with higher age ( p < 0.001), worse performance status ( p = 0.005) and higher risk profile ( p < 0.001) than the other two treatment groups. Number of metastases and sites and tumour histology did not differ between groups. Results. First line immunotherapy gave a median OS of 16.3 months and first line TKIs 10.9 months ( p = 0.003). Survival longer than 5 years was limited to immunotherapy. Sarcomatoid component, metastatic sites, papillary histology, stage, performance status and white cell blood count were related to poor OS. Using multivariate analyses to adjust for risk predictors the difference in OS disappeared. Median OS before and after introduction of TKIs was 16 months and 14 months, respectively ( p = 0.189). Memorial Sloan Kettering Cancer Center (MSKCC) risk groups were related to OS ( p < 0.001). Heng's prognostic criteria appeared slightly more predictive than MSKCC ( p = 0.12). Metastasectomy ( n = 42) may improve OS [surgery: median OS 18.8 months, 95% confidence interval (CI) 12.3-48.5; no surgery: median OS 15 months, 95% CI 10.4-16.5; p = 0.07]. Conclusions. MSKCC and Heng's prognostic algorithms were valid for prognostication and can be used for individual planning of treatment and follow-up. Surgical removal of metastases may improve OS. [ABSTRACT FROM AUTHOR]

Background Vascular endothelial growth factor (VEGF)-targeted therapy is administered continuously until progression in metastatic clear cell renal cancer (mRCC). The role of intermittent therapy is under investigation. Preclinical data raise concerns about this approach. Materials and methods This study combined the data from three similar phase II studies investigating VEGF-targeted therapy prior to planned nephrectomy for untreated mRCC (European Union Drug Regulating Authorities Clinical Trials 2006-004511-21, 2006-006491-38 and 2009-016675-29). The significance of progression during the planned treatment break (median 4.3 weeks) was assessed. Results Sixty-two patients had a structured treatment interruption for nephrectomy after achieving clinical benefit from treatment and restarted therapy. Twenty-three of these patients (37%) progressed (Response Evaluation Criteria In Solid Tumors v1.1) on the first scan after the treatment break. Subsequent stabilisation of disease occurred in 16 of the 23 (70%) progressing patients when the same VEGF tyrosine kinase inhibitor (TKI) was reintroduced. Baseline characteristics, such as the Memorial Sloan Kettering Cancer Centre prognostic score, did not predispose to the development of this progression. Progression during the treatment break was associated with an increased risk of death on multivariate analysis {hazard ratio (HR) 5.56; [95% confidence interval 2.29–13.5], P < 0.01}. Sequential fluorodeoxyglucose positron emission tomography showed a rebound in metabolic activity during the treatment break. Conclusions Progression during planned VEGF TKI treatment interruptions is frequent and associated with a poor prognosis. Treatment cessation should be pursued with caution. [ABSTRACT FROM PUBLISHER]

New combinations of antiangiogenic tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors (ICI) or dual ICI have been shown to be effective in phase III trials compared to sunitinib in the first-line treatment of metastatic renal cell cancer. While ICI doublet is already used in other indications, TKI/ICI combinations are more recent and the management of their adverse effects (AEs) are less well known, particularly with regard to the accountability of each therapeutic class. The objective of this article is to analyze the safety data from the main phase III studies to provide clinicians with practical advice for managing the AEs from these combinations. Their management depends largely on the type of combination and their grade. In the case of a TKI/ICI combination, discontinuation of the 2 molecules is considered from grade 2. Rapid improvement in symptoms suggests that the AE is related to the TKI. It is then possible, after resolution, to reintroduce the TKI, if needed by reducing the dose, and to continue the ICI. Otherwise, the blame falls on the ICI and treatment usually involves corticosteroids. Management also depends on the type of AE and its severity. In some cases (dysthyroidism), treatment with TKI/ICI may be continued. In other situations (cardiac or neurological toxicity), it should be discontinued from grade 1 and hospitalization and corticosteroid therapy should be considered immediately. In all cases, information and education are integral parts of the prevention and proper management of potential AEs., (Copyright © 2022. Published by Elsevier Masson SAS.)

Abstract: Background: Both sunitinib and pazopanib are widely used as first line therapy in metastatic renal cancer (mRCC). The efficacy of these agents appears similar but they may have distinct toxicity profiles. In this study we compare the severity of symptomatic and asymptomatic toxicity associated with sunitinib and pazopanib. Methods: Two sequential prospective single arm phase II studies investigated either 12weeks of sunitinib (n =43) or pazopanib (n =34) prior to nephrectomy in untreated mRCC. Toxicity was defined as either symptomatic (hand and foot syndrome, mucositis, nausea, fatigue, diarrhoea, oedema, headache, pain, anorexia and change in taste) or asymptomatic (liver toxicity or haematological toxicity). Pazopanib (800mg once daily (OD)) and sunitinib (50mg 4/2) were given. Regular Common Toxicity Criteria (CTC) toxicity assessment was performed during the first 12weeks of therapy. Results: There was no significant difference in the overall number of toxic events (grade 1–4) for sunitinib and pazopanib (mean number of toxic events/patients: 1.97 versus 1.96: p >0.05). Increased grade 2–4 symptomatic toxicity events occurred with sunitinib (hazard ratio (HR) 1.67 [95% confidence interval (CI): 1.11–2.56] p <0.03). Sunitinib was associated with an increased grade 2–4 mucositis (16% versus 0% p =0.02) and fatigue (42% versus 15% p =0.01). Pazopanib was associated with more frequent grade 1 diarrhoea (39% versus 12%: p =0.03). Dose reductions for symptomatic toxicity occurred more frequently with sunitinib (26% versus 6% p <0.05). There was no difference in the occurrence of asymptomatic toxicity. Conclusion: This indirect analysis suggests sunitinib and pazopanib have distinct toxicity profiles which may help guide patient’s choice. Further comparative data from randomised trials are awaited. [Copyright &y& Elsevier]

The introduction of targeted agents has substantially improved treatment of metastatic clear-cell renal cell carcinoma (RCC). However, complete responses are rare and therapy is not curative. Moreover, information on the latest generation of potent and selective vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKI) suggests that a plateau has been reached in terms of efficacy. Recent data reveal that targeted agents are involved in modulating immune responses in RCC. In addition, current research adds to our understanding of how RCC escapes an effective anti-tumor response with the potential to modulate these processes by drug development. This review provides specific insight into targeted therapy induced changes in the immunological microenvironment of RCC, summarizes the available evidence, and discusses potential therapeutic implications. [ABSTRACT FROM AUTHOR]