Sergio Bracarda - Academia.edu (original) (raw)

Papers by Sergio Bracarda

The Prostate, 2006

BACKGROUND. 2-CADO inhibits the growth of several types of cells and causes apoptosis by a mechan... more BACKGROUND. 2-CADO inhibits the growth of several types of cells and causes apoptosis by a mechanism which involves adenosine receptors or cellular uptake or both. METHODS. Androgen-independent (PC3) prostate cancer cells were used in the study and proliferation, cell-cycle progression, and apoptosis analyzed. Deoxy-and ribonucleoside triphosphate pools were determined by HPLC. The molecular mechanism was examined by assessing the involvement of DNA synthesizing enzymes in the cellular response. RESULTS. 2-CADO treatment dramatically reduced the number of prostate cancer cells and permanently stopped cell-cycle progression in the S-phase. The role of 2-CADO in prostate cancer cells is uptake-mediated and followed by sequential phosphorylations to 2-Cl-ATP that irreversibly inhibits several key-enzymes for DNA biosynthesis. CONCLUSIONS. Arrest of DNA synthesis responsible for toxicity of 2-CADO to PC3 cells is due to the lack of substrates for DNA polymerization caused by irreversible inhibition of purine/pyrimidine ribo-and 2-deoxyribonucleotides salvage enzymes.

The Prostate, 2008

BACKGROUND. Docetaxel-based chemotherapy is the only treatment that demonstrated an overall survi... more BACKGROUND. Docetaxel-based chemotherapy is the only treatment that demonstrated an overall survival benefit in men with hormone refractory prostate cancer. 2-CADO inhibits the growth of PC3 cells by inducing apoptosis and cell cycle arrest through a mechanism that involves cellular uptake. METHODS. Androgen-independent and -sensitive (PC3 and LNCaP) prostate cancer cells and non-neoplastic HECV cells were used in the study. Proliferation and cell cycle progression were analyzed in the presence of 2-CADO and Docetaxel. Invasive potential was assessed by soft agar assay and metastatic ability by adhesion assay. IL-23 and PAR-1 expression were determined by real time PCR. RESULTS. 2-CADO pre-treatment followed by Docetaxel at subclinical dosage reduced the viability of either PC3 or LNCaP while it did not enhance Docetaxel-induced cytotoxicity in adherent non-neoplastic HECV. The drugs reduced the invasive potential of PC3 cells by inducing apoptosis and blocking cell cycle progression in the S-phase. Down-regulation of PAR-1 gene expression resulted in a slightly lower metastatic potential, whereas up-regulation of IL-23 induced the activation of the immune system. CONCLUSIONS. Pretreatment of PC3 cells with 2-CADO decreased the effective concentration of Docetaxel, lowered the metastatic potential, and induced the production of cytokines known to stimulate the immune response against cancer. The treatment was effective for prostate cancer cells independently on their androgen sensitiveness.

Molecular Genetics and Metabolism, 2006

EGFR, highly expressed in a variety of human malignancies, is correlated with poor tumour diVeren... more EGFR, highly expressed in a variety of human malignancies, is correlated with poor tumour diVerentiation, high tumour growth and metastatic rate. EGF and several other ligands, such as transforming growth factor-, amphiregulin, heparin-binding EGF, and betacellulin, activate Ras/Raf mitogen-activated protein kinases (MAPKs) and phosphatidyl inositol 3Ј-kinase (PI3K)/Akt signalling pathways. Therefore, EGFR can regulate multiple processes, i.e., gene expression, cellular proliferation, angiogenesis, and inhibition of apoptosis, which contribute to the development of malignancy. In this review, we discuss the inhibition of EGFR by the speciWc tyrosine kinase inhibitor Iressa (ZD1839) focusing on its eVects in prostate cancer.

Critical Reviews in Oncology/Hematology, 2012

Cutaneous adverse events commonly reported with tyrosine kinase inhibitors (TKIs) in the treatmen... more Cutaneous adverse events commonly reported with tyrosine kinase inhibitors (TKIs) in the treatment of malignancies, represent an important clinical concern since they can limit the optimal use of these novel drugs. Although there are numerous reports in the literature of these events there are no practical guidelines on how they should be managed. The Sorafenib Working Group (SWG) was established with the objective of developing recommendations to allow the early detection, prevention and management of cutaneous adverse events in everyday clinical practice. The SWG was a multidisciplinary team made up of experts in the field who were closely involved in the sorafenib clinical development program. This review provides an overview of the nature and incidence of cutaneous adverse events which manifest with sorafenib treatment and provides recommendations for their early detection and effective management in clinical practice.

BMC Cancer, 2010

Background: Hormone therapy plus radiotherapy significantly decreases recurrences and mortality o... more Background: Hormone therapy plus radiotherapy significantly decreases recurrences and mortality of patients affected by locally advanced prostate cancer. In order to determine if difference exists according to the hormonal treatment duration, a literature-based meta-analysis was performed.

Expert review of anticancer therapy, 2017

Currently, sunitinib is a standard of care in first-line treatment for metastatic renal cell carc... more Currently, sunitinib is a standard of care in first-line treatment for metastatic renal cell carcinoma (mRCC). However, with the standard 4/2 schedule (sunitinib 50 mg/day; 4 consecutive weeks on treatment; 2 weeks' rest), 50% of patients require dose reductions to mitigate toxicity, highlighting the need to investigate alternative dosing schedules that improve tolerability without compromising efficacy. Areas covered: We present a concise critical review of published studies comparing the efficacy and safety of the 4/2 and 2/1 schedule (2 weeks on treatment; 1 week rest) for sunitinib. While all studies evaluating the 2/1 schedule have a low level of evidence, the results indicate that the 2/1 schedule improves tolerability compared with the 4/2 schedule, including significant reductions in the incidence of specific adverse events. It was not possible to make any definitive conclusions regarding efficacy due to methodologic limitations of these studies. Expert commentary: In th...

Aging clinical and experimental research, Jan 24, 2017

The Pros-IT CNR project aims to monitor a sample of Italian males ≥18 years of age who have been ... more The Pros-IT CNR project aims to monitor a sample of Italian males ≥18 years of age who have been diagnosed in the participating centers with incident prostate cancer, by analyzing their clinical features, treatment protocols and outcome results in relation to quality of life. Pros-IT CNR is an observational, prospective, multicenter study. The National Research Council (CNR), Neuroscience Institute, Aging Branch (Padua) is the promoting center. Ninety-seven Italian centers located throughout Italy were involved. The field study began in September 1, 2014. Subjects eligible were diagnosed with biopsy-verified prostate cancer, naïve. A sample size of 1500 patients was contemplated. A baseline assessment including anamnestic data, clinical history, risk factors, the initial diagnosis, cancer staging information and quality of life (Italian UCLA Prostate Cancer Index; SF-12 Scale) was completed. Six months after the initial diagnosis, a second assessment evaluating the patient's hea...

Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Jan 10, 2012

253 Background: A significant number of docetaxel (D) refractory mCRPC patients (pts) have a life... more 253 Background: A significant number of docetaxel (D) refractory mCRPC patients (pts) have a life expectancy of > 15 months and ask for additional efficacious treatments. In the phase 3 TROPIC trial treatment of mCRPC patients with CbzP who progressed during or after docetaxel resulted in a statistically significant overall survival benefit compared with mitoxantrone / prednisone (Lancet 2010). This survival benefit supported establishment of a global early access program (EAP), allowing pts with mCRPC to have access to the drug prior to its commercial availability. Here we describe preliminary safety results from the EAP in Italy. We report here the data of the first 16 mCRPC patients (out of the 123 enrolled by 19 Italian centers until Sept 2011 in EAP) treated with Cbz (25mg/m(2) Q3W) plus P(10mg bid). Pts were median age 73.5 years (>75 years 38%), ECOG PS-0 81.3% and had received a median of 7 prior cycles of D (median cumulative D dose 562.5mg). Median time from last D d...

European journal of cancer (Oxford, England : 1990), 2016

Papillary histology accounts for 10-15% of renal cell carcinoma (RCC), and treatment options for ... more Papillary histology accounts for 10-15% of renal cell carcinoma (RCC), and treatment options for patients with this subtype are limited. The RAPTOR (RAD001 in Advanced Papillary Tumor Program in Europe; ClinicalTrials.gov, NCT00688753) study evaluated first-line everolimus in patients with papillary metastatic RCC (mRCC). This phase 2 trial enrolled previously untreated patients with type 1 or type 2 papillary mRCC. Papillary histology was confirmed by central review and was performed for every patient. Patients received oral everolimus 10 mg once daily until disease progression or unacceptable toxicity. The primary end-point was progression-free survival (PFS) rate at 6 months among the first 44 patients of the per protocol (PP) population. Secondary end-points included PFS, tumour response, overall survival (OS), and safety. Analysis sets included safety (N = 92; 100%), intent-to-treat (ITT) (n = 88), and PP populations (n = 46). In the safety population, most patients were men (7...

Http Dx Doi Org 10 2217 Fon 13 46, May 29, 2013

The objectives of this innovative meeting were to discuss developments in the management of genit... more The objectives of this innovative meeting were to discuss developments in the management of genitourinary cancer worldwide and how Italian clinicians could harness these innovations in their everyday practice. The 2-day meeting was divided into two sessions covering kidney and prostate cancer, and a large part was given over to the presentation and discussion of new recently presented data at major international congresses in 2012. There were no restrictions on content and all subjects from pathology, surgery and genetics to therapy and patient outcomes were covered.

assessing the treatment of prostate cancer within the context of a multidisciplinary team. It enc... more assessing the treatment of prostate cancer within the context of a multidisciplinary team. It encompasses a broad range of topical issues, including the definition of hormone resistance, opportunities for introducing chemotherapy at earlier stages of the disease, and how urologists, medical oncologists, and radiation therapists can work together to identify these opportunities.

Clinical genitourinary cancer, Jan 27, 2016

Hyperglycemia and hypercholesterolemia are class effects of mammalian target of rapamycin inhibit... more Hyperglycemia and hypercholesterolemia are class effects of mammalian target of rapamycin inhibitors. The purpose of this study was to characterize safety and efficacy of patients with metastatic renal cell carcinoma (mRCC) treated with everolimus in RECORD-1 (REnal Cell cancer treatment with Oral RAD001 given Daily) and REACT (RAD001 Expanded Access Clinical Trial in RCC) who developed these events. Adults with vascular endothelial growth factor-refractory mRCC received everolimus 10 mg/d in the randomized RECORD-1 (n = 277) and open-label REACT (n = 1367) studies. Outcomes included safety, treatment duration, overall response, and progression-free survival for patients who developed hypercholesterolemia or hyperglycemia. In RECORD-1, 12% (33 of 277) and 20% (55 of 277) of patients developed any grade hyperglycemia or hypercholesterolemia, respectively, with only 6% (78 of 1367) and 1% (14 of 1367) of the same events, respectively, in REACT. Median everolimus treatment duration was...

European Urology Supplements, Nov 1, 2009

European Urology Supplements, 2008

European Urology, Feb 1, 1996

Future oncology (London, England), Jan 5, 2015

We evaluated the possible advantages of a docetaxel (DCT) rechallenge strategy in metastatic cast... more We evaluated the possible advantages of a docetaxel (DCT) rechallenge strategy in metastatic castration-resistant prostate cancer (mCRPC) patients, also given the possible earlier positioning of this treatment option in the modern scenario. All mCRPC patients planned for DCT chemotherapy rechallenge in our institutions were evaluated. Of 128 patients, 98 achieved disease control on the initial DCT round. After a treatment holiday of 8.3 months, the 98 responsive patients underwent a second DCT round, with 56 cases achieving again disease control. After a 5.7-month off-treatment period, 32 of these cases underwent a third DCT round, and 16 responded. Lastly, after a further 4.2-month treatment holiday, eight patients underwent a fourth DCT round and two responded. Median time to definitive disease progression for the whole population was 16.4 months. Rechallenge with DCT may be considered a suitable treatment option for mCRPC patients recurring after a successful DCT chemotherapy. Th...

The European Advanced Renal Cell Carcinoma Sorafenib (EU-ARCCS) expanded-access study provided so... more The European Advanced Renal Cell Carcinoma Sorafenib (EU-ARCCS) expanded-access study provided sorafenib to advanced renal cell carcinoma (RCC) patients in whom previous systemic therapy had failed. The study assessed the safety and use of sorafenib for the treatment of advanced RCC in a large community-based patient population across 11 countries in Europe. EU-ARCCS was a single-arm, open-label trial of sorafenib

Future oncology (London, England), Jan 17, 2015

RAD001 Expanded Access Clinical Trial (REACT) provided everolimus to patients with metastatic RCC... more RAD001 Expanded Access Clinical Trial (REACT) provided everolimus to patients with metastatic RCC before its commercial availability. This retrospective subgroup analysis evaluated eventual differences, mainly in safety, between the large European population (n = 906; 66.3%) and the overall population (n = 1367). REACT enrolled patients from 34 countries who received everolimus 10 mg/day until progression/discontinuation or commercial availability. Baseline characteristics, except race/ethnicity, were similar. Incidences of grade 3/4 adverse events were 50.7/11.3% in the European population and 48.8/12.8% in the overall population. A similar percentage of the European and overall populations achieved stable disease (˜51%) and completed treatment (20.6 and 19.7%). These results do not suggest differences for the European population and support everolimus as a worldwide standard of care for VEGFR-refractory metastatic RCC (NCT00655252).

The Prostate, 2006

BACKGROUND. 2-CADO inhibits the growth of several types of cells and causes apoptosis by a mechan... more BACKGROUND. 2-CADO inhibits the growth of several types of cells and causes apoptosis by a mechanism which involves adenosine receptors or cellular uptake or both. METHODS. Androgen-independent (PC3) prostate cancer cells were used in the study and proliferation, cell-cycle progression, and apoptosis analyzed. Deoxy-and ribonucleoside triphosphate pools were determined by HPLC. The molecular mechanism was examined by assessing the involvement of DNA synthesizing enzymes in the cellular response. RESULTS. 2-CADO treatment dramatically reduced the number of prostate cancer cells and permanently stopped cell-cycle progression in the S-phase. The role of 2-CADO in prostate cancer cells is uptake-mediated and followed by sequential phosphorylations to 2-Cl-ATP that irreversibly inhibits several key-enzymes for DNA biosynthesis. CONCLUSIONS. Arrest of DNA synthesis responsible for toxicity of 2-CADO to PC3 cells is due to the lack of substrates for DNA polymerization caused by irreversible inhibition of purine/pyrimidine ribo-and 2-deoxyribonucleotides salvage enzymes.

The Prostate, 2008

BACKGROUND. Docetaxel-based chemotherapy is the only treatment that demonstrated an overall survi... more BACKGROUND. Docetaxel-based chemotherapy is the only treatment that demonstrated an overall survival benefit in men with hormone refractory prostate cancer. 2-CADO inhibits the growth of PC3 cells by inducing apoptosis and cell cycle arrest through a mechanism that involves cellular uptake. METHODS. Androgen-independent and -sensitive (PC3 and LNCaP) prostate cancer cells and non-neoplastic HECV cells were used in the study. Proliferation and cell cycle progression were analyzed in the presence of 2-CADO and Docetaxel. Invasive potential was assessed by soft agar assay and metastatic ability by adhesion assay. IL-23 and PAR-1 expression were determined by real time PCR. RESULTS. 2-CADO pre-treatment followed by Docetaxel at subclinical dosage reduced the viability of either PC3 or LNCaP while it did not enhance Docetaxel-induced cytotoxicity in adherent non-neoplastic HECV. The drugs reduced the invasive potential of PC3 cells by inducing apoptosis and blocking cell cycle progression in the S-phase. Down-regulation of PAR-1 gene expression resulted in a slightly lower metastatic potential, whereas up-regulation of IL-23 induced the activation of the immune system. CONCLUSIONS. Pretreatment of PC3 cells with 2-CADO decreased the effective concentration of Docetaxel, lowered the metastatic potential, and induced the production of cytokines known to stimulate the immune response against cancer. The treatment was effective for prostate cancer cells independently on their androgen sensitiveness.

Molecular Genetics and Metabolism, 2006

EGFR, highly expressed in a variety of human malignancies, is correlated with poor tumour diVeren... more EGFR, highly expressed in a variety of human malignancies, is correlated with poor tumour diVerentiation, high tumour growth and metastatic rate. EGF and several other ligands, such as transforming growth factor-, amphiregulin, heparin-binding EGF, and betacellulin, activate Ras/Raf mitogen-activated protein kinases (MAPKs) and phosphatidyl inositol 3Ј-kinase (PI3K)/Akt signalling pathways. Therefore, EGFR can regulate multiple processes, i.e., gene expression, cellular proliferation, angiogenesis, and inhibition of apoptosis, which contribute to the development of malignancy. In this review, we discuss the inhibition of EGFR by the speciWc tyrosine kinase inhibitor Iressa (ZD1839) focusing on its eVects in prostate cancer.

Critical Reviews in Oncology/Hematology, 2012

Cutaneous adverse events commonly reported with tyrosine kinase inhibitors (TKIs) in the treatmen... more Cutaneous adverse events commonly reported with tyrosine kinase inhibitors (TKIs) in the treatment of malignancies, represent an important clinical concern since they can limit the optimal use of these novel drugs. Although there are numerous reports in the literature of these events there are no practical guidelines on how they should be managed. The Sorafenib Working Group (SWG) was established with the objective of developing recommendations to allow the early detection, prevention and management of cutaneous adverse events in everyday clinical practice. The SWG was a multidisciplinary team made up of experts in the field who were closely involved in the sorafenib clinical development program. This review provides an overview of the nature and incidence of cutaneous adverse events which manifest with sorafenib treatment and provides recommendations for their early detection and effective management in clinical practice.

BMC Cancer, 2010

Background: Hormone therapy plus radiotherapy significantly decreases recurrences and mortality o... more Background: Hormone therapy plus radiotherapy significantly decreases recurrences and mortality of patients affected by locally advanced prostate cancer. In order to determine if difference exists according to the hormonal treatment duration, a literature-based meta-analysis was performed.

Expert review of anticancer therapy, 2017

Currently, sunitinib is a standard of care in first-line treatment for metastatic renal cell carc... more Currently, sunitinib is a standard of care in first-line treatment for metastatic renal cell carcinoma (mRCC). However, with the standard 4/2 schedule (sunitinib 50 mg/day; 4 consecutive weeks on treatment; 2 weeks' rest), 50% of patients require dose reductions to mitigate toxicity, highlighting the need to investigate alternative dosing schedules that improve tolerability without compromising efficacy. Areas covered: We present a concise critical review of published studies comparing the efficacy and safety of the 4/2 and 2/1 schedule (2 weeks on treatment; 1 week rest) for sunitinib. While all studies evaluating the 2/1 schedule have a low level of evidence, the results indicate that the 2/1 schedule improves tolerability compared with the 4/2 schedule, including significant reductions in the incidence of specific adverse events. It was not possible to make any definitive conclusions regarding efficacy due to methodologic limitations of these studies. Expert commentary: In th...

Aging clinical and experimental research, Jan 24, 2017

The Pros-IT CNR project aims to monitor a sample of Italian males ≥18 years of age who have been ... more The Pros-IT CNR project aims to monitor a sample of Italian males ≥18 years of age who have been diagnosed in the participating centers with incident prostate cancer, by analyzing their clinical features, treatment protocols and outcome results in relation to quality of life. Pros-IT CNR is an observational, prospective, multicenter study. The National Research Council (CNR), Neuroscience Institute, Aging Branch (Padua) is the promoting center. Ninety-seven Italian centers located throughout Italy were involved. The field study began in September 1, 2014. Subjects eligible were diagnosed with biopsy-verified prostate cancer, naïve. A sample size of 1500 patients was contemplated. A baseline assessment including anamnestic data, clinical history, risk factors, the initial diagnosis, cancer staging information and quality of life (Italian UCLA Prostate Cancer Index; SF-12 Scale) was completed. Six months after the initial diagnosis, a second assessment evaluating the patient's hea...

Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Jan 10, 2012

253 Background: A significant number of docetaxel (D) refractory mCRPC patients (pts) have a life... more 253 Background: A significant number of docetaxel (D) refractory mCRPC patients (pts) have a life expectancy of > 15 months and ask for additional efficacious treatments. In the phase 3 TROPIC trial treatment of mCRPC patients with CbzP who progressed during or after docetaxel resulted in a statistically significant overall survival benefit compared with mitoxantrone / prednisone (Lancet 2010). This survival benefit supported establishment of a global early access program (EAP), allowing pts with mCRPC to have access to the drug prior to its commercial availability. Here we describe preliminary safety results from the EAP in Italy. We report here the data of the first 16 mCRPC patients (out of the 123 enrolled by 19 Italian centers until Sept 2011 in EAP) treated with Cbz (25mg/m(2) Q3W) plus P(10mg bid). Pts were median age 73.5 years (>75 years 38%), ECOG PS-0 81.3% and had received a median of 7 prior cycles of D (median cumulative D dose 562.5mg). Median time from last D d...

European journal of cancer (Oxford, England : 1990), 2016

Papillary histology accounts for 10-15% of renal cell carcinoma (RCC), and treatment options for ... more Papillary histology accounts for 10-15% of renal cell carcinoma (RCC), and treatment options for patients with this subtype are limited. The RAPTOR (RAD001 in Advanced Papillary Tumor Program in Europe; ClinicalTrials.gov, NCT00688753) study evaluated first-line everolimus in patients with papillary metastatic RCC (mRCC). This phase 2 trial enrolled previously untreated patients with type 1 or type 2 papillary mRCC. Papillary histology was confirmed by central review and was performed for every patient. Patients received oral everolimus 10 mg once daily until disease progression or unacceptable toxicity. The primary end-point was progression-free survival (PFS) rate at 6 months among the first 44 patients of the per protocol (PP) population. Secondary end-points included PFS, tumour response, overall survival (OS), and safety. Analysis sets included safety (N = 92; 100%), intent-to-treat (ITT) (n = 88), and PP populations (n = 46). In the safety population, most patients were men (7...

Http Dx Doi Org 10 2217 Fon 13 46, May 29, 2013

The objectives of this innovative meeting were to discuss developments in the management of genit... more The objectives of this innovative meeting were to discuss developments in the management of genitourinary cancer worldwide and how Italian clinicians could harness these innovations in their everyday practice. The 2-day meeting was divided into two sessions covering kidney and prostate cancer, and a large part was given over to the presentation and discussion of new recently presented data at major international congresses in 2012. There were no restrictions on content and all subjects from pathology, surgery and genetics to therapy and patient outcomes were covered.

assessing the treatment of prostate cancer within the context of a multidisciplinary team. It enc... more assessing the treatment of prostate cancer within the context of a multidisciplinary team. It encompasses a broad range of topical issues, including the definition of hormone resistance, opportunities for introducing chemotherapy at earlier stages of the disease, and how urologists, medical oncologists, and radiation therapists can work together to identify these opportunities.

Clinical genitourinary cancer, Jan 27, 2016

Hyperglycemia and hypercholesterolemia are class effects of mammalian target of rapamycin inhibit... more Hyperglycemia and hypercholesterolemia are class effects of mammalian target of rapamycin inhibitors. The purpose of this study was to characterize safety and efficacy of patients with metastatic renal cell carcinoma (mRCC) treated with everolimus in RECORD-1 (REnal Cell cancer treatment with Oral RAD001 given Daily) and REACT (RAD001 Expanded Access Clinical Trial in RCC) who developed these events. Adults with vascular endothelial growth factor-refractory mRCC received everolimus 10 mg/d in the randomized RECORD-1 (n = 277) and open-label REACT (n = 1367) studies. Outcomes included safety, treatment duration, overall response, and progression-free survival for patients who developed hypercholesterolemia or hyperglycemia. In RECORD-1, 12% (33 of 277) and 20% (55 of 277) of patients developed any grade hyperglycemia or hypercholesterolemia, respectively, with only 6% (78 of 1367) and 1% (14 of 1367) of the same events, respectively, in REACT. Median everolimus treatment duration was...

European Urology Supplements, Nov 1, 2009

European Urology Supplements, 2008

European Urology, Feb 1, 1996

Future oncology (London, England), Jan 5, 2015

We evaluated the possible advantages of a docetaxel (DCT) rechallenge strategy in metastatic cast... more We evaluated the possible advantages of a docetaxel (DCT) rechallenge strategy in metastatic castration-resistant prostate cancer (mCRPC) patients, also given the possible earlier positioning of this treatment option in the modern scenario. All mCRPC patients planned for DCT chemotherapy rechallenge in our institutions were evaluated. Of 128 patients, 98 achieved disease control on the initial DCT round. After a treatment holiday of 8.3 months, the 98 responsive patients underwent a second DCT round, with 56 cases achieving again disease control. After a 5.7-month off-treatment period, 32 of these cases underwent a third DCT round, and 16 responded. Lastly, after a further 4.2-month treatment holiday, eight patients underwent a fourth DCT round and two responded. Median time to definitive disease progression for the whole population was 16.4 months. Rechallenge with DCT may be considered a suitable treatment option for mCRPC patients recurring after a successful DCT chemotherapy. Th...

The European Advanced Renal Cell Carcinoma Sorafenib (EU-ARCCS) expanded-access study provided so... more The European Advanced Renal Cell Carcinoma Sorafenib (EU-ARCCS) expanded-access study provided sorafenib to advanced renal cell carcinoma (RCC) patients in whom previous systemic therapy had failed. The study assessed the safety and use of sorafenib for the treatment of advanced RCC in a large community-based patient population across 11 countries in Europe. EU-ARCCS was a single-arm, open-label trial of sorafenib

Future oncology (London, England), Jan 17, 2015

RAD001 Expanded Access Clinical Trial (REACT) provided everolimus to patients with metastatic RCC... more RAD001 Expanded Access Clinical Trial (REACT) provided everolimus to patients with metastatic RCC before its commercial availability. This retrospective subgroup analysis evaluated eventual differences, mainly in safety, between the large European population (n = 906; 66.3%) and the overall population (n = 1367). REACT enrolled patients from 34 countries who received everolimus 10 mg/day until progression/discontinuation or commercial availability. Baseline characteristics, except race/ethnicity, were similar. Incidences of grade 3/4 adverse events were 50.7/11.3% in the European population and 48.8/12.8% in the overall population. A similar percentage of the European and overall populations achieved stable disease (˜51%) and completed treatment (20.6 and 19.7%). These results do not suggest differences for the European population and support everolimus as a worldwide standard of care for VEGFR-refractory metastatic RCC (NCT00655252).