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1.
Urologe A ; 59(2): 162-168, 2020 Feb.
Article in German | MEDLINE | ID: mdl-32047953

ABSTRACT

BACKGROUND: Renal cell carcinoma is the third most common tumor of the genitourinary system. Small tumors are increasingly treated by nephron-sparing surgery, focal therapy via cryoablation or radiofrequency ablation and also active surveillance. These treatment options are associated with increased follow-up care. OBJECTIVES: What are the current recommendations on follow-up care for different therapeutic approaches in renal cell carcinoma? MATERIALS AND METHODS: We analyzed different biological aspects regarding renal cell carcinoma, diagnostic procedures as well as recommendations of current guidelines (e.g. German S3, EAU AUA). RESULTS: Follow-up of renal cell carcinoma is not well standardized due to the limited amount of data. In general, follow-up should be intensified during the first 3 years following initial therapy as well as in patients with increased risk for tumor recurrence. For risk calculation different prognostic models based on clinical parameters have been published. CONCLUSIONS: Current recommendations on follow-up care in renal cell carcinoma are based on retrospective studies. Future strategies must include markers and be studied in a prospective manner.


Subject(s)
Aftercare/methods , Carcinoma, Renal Cell/surgery , Kidney Neoplasms/surgery , Kidney/pathology , Neoplasm Recurrence, Local/prevention & control , Carcinoma, Renal Cell/pathology , Follow-Up Studies , Humans , Kidney Neoplasms/pathology , Neoplasm Staging , Nephrectomy , Retrospective Studies , Treatment Outcome
3.
Aktuelle Urol ; 43(4): 219-26, 2012 Jul.
Article in German | MEDLINE | ID: mdl-23035262

ABSTRACT

Immune and targeted therapy represent innovative therapy options in oncology. An overview of novel immune and targeted therapy options in urologic oncology presented at the most recent scientific urological and oncological meetings is given by representatives of the German Association of Immune and Targeted Therapy (DGFIT). Besides renal cell cancer, where targeted therapy is well established, new immune and targeted approaches in prostate and bladder cancer are discussed, summarizing current results and new developments with relevant impact for the treating physician.


Subject(s)
Antineoplastic Agents/administration & dosage , Cancer Vaccines/administration & dosage , Drug Delivery Systems/methods , Molecular Targeted Therapy/methods , Urogenital Neoplasms/therapy , Antineoplastic Agents/adverse effects , Cancer Vaccines/adverse effects , Carcinoma, Renal Cell/secondary , Carcinoma, Renal Cell/therapy , Carcinoma, Transitional Cell/secondary , Carcinoma, Transitional Cell/therapy , Disease Progression , Double-Blind Method , Drug Delivery Systems/adverse effects , Female , Humans , Kidney Neoplasms/therapy , Male , Prostatic Neoplasms/therapy , Randomized Controlled Trials as Topic , Urinary Bladder Neoplasms/therapy
4.
Aktuelle Urol ; 43(4): 243-9, 2012 Jul.
Article in German | MEDLINE | ID: mdl-22869494

ABSTRACT

The incidence of renal cell carcinoma (RCC) and especially that of small RCCs is increasing. However, not all tumours are malignant and not all malignant tumours are RCCs. Although partial nephrectomy is the therapeutic standard of care, an increasing number of patients is being treated with cryoablation, radiofrequency ablation, or active surveillance. The latter options require a pretherapeutic tumour biopsy. Approximately 85% of all biopsies can distinguish benign from malignant tumours. In the case of a RCC, histological subtype and grading are correctly diagnosed in 85% and 65%, respectively. However, tumour growth and metastasis in patients undergoing active surveillance cannot be predicted. A later tumour growth is the main trigger to change to active therapy. In this paper the results of tumour biopsy and active surveillance of patients with a renal mass are presented.


Subject(s)
Carcinoma, Renal Cell/therapy , Kidney Neoplasms/therapy , Watchful Waiting , Biopsy , Carcinoma, Renal Cell/diagnosis , Carcinoma, Renal Cell/pathology , Early Diagnosis , Humans , Incidental Findings , Kidney/pathology , Kidney Neoplasms/diagnosis , Kidney Neoplasms/pathology , Nephrectomy , Prognosis , Tumor Burden
5.
Rofo ; 184(2): 130-5, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22274854

ABSTRACT

PURPOSE: False-negative results are obtained in approx. 20 % of prostate cancer (PCa) patients (pts) at initial systematic transrectal biopsy (Bx), in particular when digital rectal examination (DRE) or transrectal ultrasound (TRUS) is negative. The aim of this study was to assess whether MR endorectal imaging of the prostate in a multi-reader ambulatory care setting may assist in patient selection for re-biopsy. MATERIALS AND METHODS: 115 consecutive pts with persistent PSA elevation, negative Bx, DRE and TRUS were examined using T2w axial and coronal and T1w axial sequences for tumor diagnosis. MR images were prospectively read as tumor-suspicious or tumor-negative by the MR radiologist on duty. Additionally, a retrospective readout of a prostate MR expert and an abdominal imaging fellowship-trained radiologist was performed to evaluate the effect of the reader's experience on tumor detection. Imaging findings were compared to the results of the repeat Bx (61 pts) or the clinical course of at least two years. RESULTS: For the prospective reading, the sensitivity of MRI was 83 %, the specificity was 69 %, the PPV was 33 % and the NPV was 96 %. ROC analysis revealed a significantly better performance of the prostate MR imaging expert compared to the abdominal imaging radiologist (area under ROC 0.88 vs. 0.66, p < 0.001). Based on the prospective reading, a pre-test probability for PCa of 17.4 % as in our study can be reduced to 5 % when obtaining a tumor-negative result in MRI. CONCLUSION: MR imaging in a multi-reader ambulatory care setting assists in patient selection for re-biopsy. Reducing the post-test probability for PCa to 5 % allows for further follow-up instead of re-biopsy in MR tumor-negative patients. Specific training and experience improve tumor detection in prostate MR imaging.


Subject(s)
Biomarkers, Tumor/blood , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Prostate-Specific Antigen/blood , Prostate/pathology , Prostatic Neoplasms/diagnosis , Aged , Ambulatory Care , Biopsy , Cohort Studies , Diagnosis, Differential , False Negative Reactions , Follow-Up Studies , Humans , Male , Middle Aged , Observer Variation , Prospective Studies , Prostatic Hyperplasia/blood , Prostatic Hyperplasia/diagnosis , Prostatic Hyperplasia/pathology , Prostatic Neoplasms/blood , Prostatic Neoplasms/pathology , Prostatitis/blood , Prostatitis/diagnosis , Prostatitis/pathology , ROC Curve
6.
Scand J Urol Nephrol ; 46(1): 44-7, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22077963

ABSTRACT

OBJECTIVE: Urinary retention frequently occurs in patients after kidney transplantation. This study aimed to identify predictive factors for urinary retention requiring transurethral resection of the prostate (TURP) following kidney transplantation. MATERIAL AND METHODS: Seventy male patients (median age 56 years, range 37-73 years) who underwent kidney transplantation between 1995 and 2006, and experienced urinary retention and consecutively required TURP, were studied retrospectively. Residual diuresis before transplantation, duration of dialysis, patient age, prostate size, rejection reactions, transplant loss, combined kidney and pancreas transplantation, type 1 and 2 diabetes mellitus, and carcinoma of the prostate were evaluated as predictive factors. RESULTS: Duration of dialysis longer than 120 months (p = 0.0174), patient age over 60 years (p = 0.0045) and the absence of diabetes (n = 46, p = 0.0029) were associated with a significantly higher risk of urinary retention requiring TURP following kidney transplantation. Residual diuresis, prostate size, frequency of rejection reactions, transplant loss and detection of carcinoma, however, could not be identified as predictive factors. CONCLUSIONS: In male patients after kidney transplantation with a long history of dialysis, early TURP due to urinary retention must be anticipated. Surprisingly, the presence of type 1 or 2 diabetes seems to prevent the occurrence of retention, independently of age.


Subject(s)
Diabetes Mellitus/epidemiology , Kidney Failure, Chronic/epidemiology , Kidney Failure, Chronic/therapy , Kidney Transplantation , Renal Dialysis , Urinary Retention/epidemiology , Adult , Age Factors , Aged , Comorbidity , Humans , Male , Middle Aged , Predictive Value of Tests , Prostate/surgery , Retrospective Studies , Risk Factors , Time Factors , Transurethral Resection of Prostate , Urinary Retention/surgery
7.
Urologe A ; 50(9): 1110-7, 2011 Sep.
Article in German | MEDLINE | ID: mdl-21559917

ABSTRACT

BACKGROUND: Since 2006 in Germany six different target drugs for therapy in metastatic renal cell cancer (mRCC) have been used. Comparative studies for the application with the same indication are absent, and the order of potential sequential therapy is up to now unclear. The aim of the study was to collect data on therapy decisions in Germany regarding mRCC in the age of "targeted therapy". At the same time the study addressed the central question of sequencing of the different therapy options. In addition, the data of this study were to be compared to a study already published in 2008. PATIENTS AND METHODS: In 2010, four groups of doctors specialized in the therapy of patients with mRCC were asked for their behaviour in the first-, second- and third-line or sequential therapy. Those questioned included urologists in private practice (n=40), oncologists in private practice (n=40), hospital urologists (n=35) and hospital oncologists (n=35). Further the reasons for a therapy decision should be stated or weighted. RESULTS: Altogether 92% of all patients with mRCC were treated. Urologists in private practice treat only 30% of their patients themselves. The earlier used immune therapies (IFN, IL-2) no longer play a role. Sunitinib is used most often in first-line therapy by urologists in private practice (50.4%) and oncologists in private practice (47.1%). In second- and third-line therapy everolimus is used by urologists in private practice (27.1%, 26.3%) and sorafenib (28.6%) or everolimus (26.4%) by oncologists in private practice. Hospital oncologists use primarily sunitinib (56.1%), in second-line sorafenib (45.5%) and in third-line above all everolimus (19.4%). Hospital urologists use sunitinib most often for first-line therapy (57.6%) and sorafenib for second-line treatment (37.3%), while in third-line therapy temsirolimus (49.6%) and also everolimus (30.4%) were used. CONCLUSIONS: The therapy of mRCC is determined very strongly by the substances sunitinib and sorafenib. The mTOR inhibitors have recently been increasingly included in the second- and third-line therapy. With the introduction of the new targeted therapies, the treatment of these special patients is performed less by urologists and increasingly more by oncologists. This trend is strengthened in comparison to the DGFIT study from 2008.


Subject(s)
Antineoplastic Agents/administration & dosage , Carcinoma, Renal Cell/drug therapy , Drug Delivery Systems , Kidney Neoplasms/drug therapy , Adult , Aged , Antineoplastic Agents/adverse effects , Benzenesulfonates/administration & dosage , Benzenesulfonates/adverse effects , Carcinoma, Renal Cell/pathology , Data Collection , Disease Progression , Everolimus , Female , Germany , Humans , Indoles/administration & dosage , Indoles/adverse effects , Kidney Neoplasms/pathology , Male , Middle Aged , Niacinamide/analogs & derivatives , Phenylurea Compounds , Practice Patterns, Physicians' , Protein-Tyrosine Kinases/antagonists & inhibitors , Pyridines/administration & dosage , Pyridines/adverse effects , Pyrroles/administration & dosage , Pyrroles/adverse effects , Sirolimus/administration & dosage , Sirolimus/adverse effects , Sirolimus/analogs & derivatives , Sorafenib , Sunitinib , TOR Serine-Threonine Kinases/antagonists & inhibitors
8.
World J Urol ; 29(1): 121-6, 2011 Feb.
Article in English | MEDLINE | ID: mdl-20512580

ABSTRACT

PURPOSE: To evaluate the efficacy and safety of WX-G250, a chimeric monoclonal antibody that binds to carboxy anhydrase IX, combined with low-dose interferon-alpha (LD-IFNα) in patients with progressive metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: Thirty-one patients, nephrectomized for the primary tumor, clear cell progressive mRCC, were enrolled to receive weekly infusions of WX-G250 (20 mg i.v.; week 2-12) combined with LD-IFNα (3 MIU s.c. 3 times/week; week 1-12). At week 16, patients were evaluated for response and stratified into two groups: (a) responders into the extended treatment group for an additional 6 weeks of treatment or (b) the progressive group with no further study treatment. RESULTS: Of the 31 treated patients, 26 were evaluable for response to treatment. Two patients showed partial remission and 14 patients had stable disease as assessed in week 16. One patient experienced partial remission resulting in a complete remission lasting at least 17 months. Nine patients had durable stable disease of 24 weeks or longer. Clinical benefit was obtained in 42% (11/26) patients. The median overall survival achieved was 30 months and the 2-year survival was 57%. Patients receiving extended treatment showed a significantly longer 2-year survival rate than discontinued patients (79 vs. 30%; P=0.0083). In general, treatment was well tolerated with little toxicity. CONCLUSION: Treatment with the antibody WX-G250 in combination with LD-IFNα is safe, well tolerated, led to clinically meaningful disease stabilization and demonstrated clinical benefit in this progressive mRCC patient population.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Interferon-alpha/therapeutic use , Kidney Neoplasms/drug therapy , Aged , Antibodies, Monoclonal/adverse effects , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/mortality , Dose-Response Relationship, Drug , Drug Therapy, Combination , Female , Humans , Interferon alpha-2 , Interferon-alpha/adverse effects , Kidney Neoplasms/mortality , Male , Middle Aged , Prospective Studies , Recombinant Proteins , Retrospective Studies , Survival Rate , Treatment Outcome
9.
Eur J Med Res ; 15: 287-91, 2010.
Article in English | MEDLINE | ID: mdl-20696639

ABSTRACT

BACKGROUND: Sarcomatoid renal cell cancer (RCC) is a distinct histological variant of RCC that is associated with rapid progression and a poor prognosis. The optimal treatment for patients with sarcomatoid RCC remains to be defined. Gemcitabine plus doxorubicine (GD) has shown some efficacy, however durability of response is limited. We carried out a prospective, open-label study to investigate the efficacy and safety of sorafenib in patients after GD failure in sarcomatoid RCC. METHODS: Fifteen patients with pure sarcomatoid RCC and objective progressive disease were treated with GD (gemcitabine 1500 mg/m², doxorubicine 50 mg/m² administered by weekly intravenous infusion) until progression of disease. Subsequently 9 patients were switched to sorafenib (400 mg twice daily). Tumor response was measured by physical examination and computerized tomography scans and evaluated according to Response Evaluation Criteria in Solid Tumors criteria. RESULTS: Median time to progression (TTP) under GD was 6.6 months (range 0.8 - 8 months). During GD treatment there were no remissions and 6 patients died from progressive disease. Median TTP for the 9 patients switched to sorafenib was 10.9 months (range 0.6 - 25.5 months). During sorafenib therapy one patient had a partial remission lasting for 3 months and 4 patients experienced stable disease with a duration of 3 to 9 months. Four patients immediately progressed on sorafenib treatment but had a slower dynamic of tumor progression than under GD. Dosing in both treatment phases was generally well tolerated with manageable toxicities and no requirement for dose reduction. CONCLUSIONS: Chemotherapy with GD was ineffective in our patients with pure sarcomatoid RCC. Subsequent anti-angiogenic treatment using the multi-tyrosine kinase inhibitor sorafenib resulted in additional progression-free survival in 5 of 9 patients. Further evaluation of targeted anti-angiogenic agents for the treatment of sarcomatoid RCC is warranted.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Benzenesulfonates/therapeutic use , Carcinoma, Renal Cell/drug therapy , Deoxycytidine/analogs & derivatives , Doxorubicin/therapeutic use , Kidney Neoplasms/drug therapy , Pyridines/therapeutic use , Adult , Aged , Aged, 80 and over , Benzenesulfonates/administration & dosage , Carcinoma, Renal Cell/diagnostic imaging , Deoxycytidine/administration & dosage , Deoxycytidine/therapeutic use , Doxorubicin/administration & dosage , Female , Humans , Kidney Neoplasms/diagnostic imaging , Male , Middle Aged , Niacinamide/analogs & derivatives , Phenylurea Compounds , Pyridines/administration & dosage , Radiography , Sorafenib , Gemcitabine
10.
Aktuelle Urol ; 41(2): 122-30, 2010 Mar.
Article in German | MEDLINE | ID: mdl-19937556

ABSTRACT

INTRODUCTION: Until recently, the standard therapy for metastatic renal cell carcinoma (mRCC) in Germany consisted of interleukin-2 (IL-2), interferon-alfa (IFN) as single agents or in combination, with or without chemotherapy. Since 2005, new drugs (target drugs) in the therapy for mRCC are available. The aim of this study was to analyse the current therapy standard in Germany. METHODS: By representative telephone interviews (GFK-Nürnberg by order of DGFIT) the following colleagues were contacted A: urologists in private practice (n = 40), B: oncologists in private practice (n = 40), C: hospital urologists (n = 35) and D: hospital oncologists (n = 35). Screening criteria were 1) responsibility for therapy in mRCC; 2) therapy of at least 10 patients with mRCC per year. RESULTS: Patients/year: A: n = 19, B: n = 17, C: n = 43, D: n = 21. 98% of patients with mRCC were treated: A: the most frequent therapy was sunitinib (43%, 42%, 33% as first-, second-, third-line), B: the most frequent therapy was sunitinib (45% as first-line, 37% as second-line), the most frequent third-line therapy was sorafenib (35%); C: the most frequent therapy were sorafenib and sunitinib (first-line 26% vs. 27%, second-line 46% vs. 42%), in third-line therapy additionally temsirolimus 24%; D: primary sorafenib and sunitinib (first-line 33% vs. 40%, second-line 46% vs. 42%), in third-line therapy additionally temsirolimus 23%. Immunotherapy (IL-2, IFN with or without chemotherapy) in mRCC plays in Germany for the second- and third-line therapy in A-D no major role (less than 10%). Otherwise, for first-line therapy immunotherapy has some relevance: A: 25%, B: 37%, C: 33%, D: 16%. The most important criteria for therapy decision making in A-D were: efficacy, toxicity, drug approval status. CONCLUSIONS: Most patients with mRCC in Germany were seen by hospital urologists. Sunitinib (in first-line) and sorafenib (in second-line) are currently the most frequent prescribed drugs in mRCC. Temsirolimus is used mostly for third-line therapy (followed by sunitinib/sorafenib). Treatment of mRCC in Germany is increasingly being performed by oncologists.


Subject(s)
Antineoplastic Agents/therapeutic use , Benzenesulfonates/therapeutic use , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/secondary , Drug Delivery Systems/methods , Immunotherapy/methods , Indoles/therapeutic use , Kidney Neoplasms/drug therapy , Pyridines/therapeutic use , Pyrroles/therapeutic use , Sirolimus/analogs & derivatives , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Attitude of Health Personnel , Cooperative Behavior , Data Collection , Drug Utilization/statistics & numerical data , Germany , Humans , Interdisciplinary Communication , Interferon-alpha/therapeutic use , Interleukin-2/therapeutic use , Medical Oncology , Niacinamide/analogs & derivatives , Patient Care Team , Phenylurea Compounds , Sirolimus/therapeutic use , Sorafenib , Sunitinib , Urology
11.
Eur J Med Res ; 13(11): 531-5, 2008 Nov 24.
Article in English | MEDLINE | ID: mdl-19073390

ABSTRACT

INTRODUCTION: Carcinoma of the collecting ducts of Bellini of the kidney (CDC) is very rare but among the most aggressive urological entities. Standard therapy is not well defined with questionable efficacy. METHODS: We present two cases of male patients (49 and 66 years old) with pT3a pN2 CDC treated with a combination of cisplatin plus gemcitabine in an adjuvant setting. Following recurrence the multi-kinase inhibitor sunitinib was administered. RESULTS: Radical nephrectomy with lymphadenectomy revealed CDC in stage pT3a pN2 M0 G3 R0 in both patients. 4 courses of adjuvant chemotherapy with cisplatin 70 mg/m superset2 and gemcitabine 1,500 mg/m superset2 were given. Side effects according to the NCI 3.0 common toxicity criteria were limited to grade 2 asthenia and grade 2 thrombozytopenia/leucopenia. Restaging revealed local recurrence and lymph node metastases. Both patients were re-operated and metastatic CDC was found. Second line therapy with sunitinb malatat (Sutent superset, Pfizer Inc. U.S.) at 50mg p.o. was given. Grade 3 leucopenia and thrombocytopenia and grade 2 asthenia and mucositis were not dose-limiting. After two cycles multiple liver, lung and bone metastases and mediastinal lymphopathy occured. 8 weeks later the patients died with a survival of 8 months from initial diagnosis. CONCLUSIONS: Adjuvant gemcitabine plus cisplatin did not delay recurrence of CDC after surgery. Metastasectomy either had no influence on the course of disease. Anti-angiogenetic therapy with sunitinib treatment was not effective, possibly related to a low vascular density (CD31 expression) in CDC.


Subject(s)
Antineoplastic Agents/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carcinoma, Renal Cell/drug therapy , Indoles/administration & dosage , Kidney Neoplasms/drug therapy , Pyrroles/administration & dosage , Aged , Antimetabolites, Antineoplastic/administration & dosage , Carcinoma, Renal Cell/pathology , Chemotherapy, Adjuvant , Cisplatin/administration & dosage , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Humans , Kidney Neoplasms/pathology , Kidney Tubules, Collecting/pathology , Male , Middle Aged , Protein-Tyrosine Kinases/antagonists & inhibitors , Sunitinib , Gemcitabine
12.
Br J Cancer ; 95(4): 463-9, 2006 Aug 21.
Article in English | MEDLINE | ID: mdl-16909131

ABSTRACT

We performed a prospectively randomised clinical trial to compare the efficacy of four subcutaneous interleukin-2-(sc-IL-2) and sc interferon-alpha2a (sc-IFN-alpha2a)-based outpatient regimens in 379 patients with progressive metastatic renal cell carcinoma. Patients with lung metastases, an erythrocyte sedimentation rate < or =70 mm h(-1) and neutrophil counts < or =6000 microl(-1) (group I) were randomised to arm A: sc-IL-2, sc-IFN-alpha2a, peroral 13-cis-retinoic acid (po-13cRA) (n=78), or arm B: arm A plus inhaled-IL-2 (n=65). All others (group II) were randomised to arm C: arm A plus intravenous 5-fluorouracil (iv-5-FU) (n=116), or arm D: arm A plus po-Capecitabine (n=120). Median overall survival (OS) was 22 months (arm A; 3-year OS: 29.7%) and 18 months (arm B; 3-year OS: 29.2%) in group I, and 18 months (arm C; 3-year OS: 25.7%) and 16 months (arm D; 3-year OS: 32.6%) in group II. There were no statistically significant differences in OS, progression-free survival, and objective response between arms A and B, and between arms C and D, respectively. Given the known therapeutic efficacy of sc-IL-2/sc-INF-alpha2a/po-13cRA-based outpatient chemoimmunotherapies, our results did not establish survival advantages in favour of po-Capecitabine vs iv-5-FU, and in favour of short-term inhaled-IL-2 in patients with advanced renal cell carcinoma receiving systemic cytokines.


Subject(s)
Carcinoma, Renal Cell/drug therapy , Interferon-alpha/administration & dosage , Interleukin-2/administration & dosage , Isotretinoin/administration & dosage , Kidney Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Capecitabine , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Disease Progression , Disease-Free Survival , Female , Fluorouracil/administration & dosage , Germany , Humans , Interferon alpha-2 , Lung Neoplasms/secondary , Male , Middle Aged , Recombinant Proteins , Survival Analysis
13.
Curr Drug Targets ; 6(7): 835-46, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16305462

ABSTRACT

Renal cell carcinoma (RCC) is a highly treatment-resistant tumor type; however, advances in elucidating the molecular pathophysiology underlying RCC has led to the identification of promising targets for therapeutic intervention. In clear-cell RCC, mutations to the von Hippel-Lindau (VHL) gene results in the up regulation of many proteins necessary for tumor growth and survival--such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and platelet derived growth factor (PDGF), which are involved in tumor-initiated angiogenesis. Carbonic anhydrase IX and signaling via the epidermal growth factor receptor (EGFR) are involved in tumor cell proliferation and are also up regulated by mutation in the VHL gene. The intracellular messenger pathways phosphoinositide 3-kinase (PI3K) and Raf/MEK/ERK act as convergence points for positive growth signaling; the Raf/MEK/ERK pathway is also implicated in apoptosis. Several agents in development target VEGF (bevacizumab), the VEGF receptor (PTK787, SU11248, VEGF-trap, and BAY 43-9006), the PDGF receptor (SU11248 and BAY 43-9006), or the EGF receptor (gefitinib, cetuximab, ABX-EGF, and erlotinib). The intracellular Raf/MEK/ERK signaling cascade has been targeted at either the level of Raf (BAY 43-9006, ISIS 5132) or MEK (CI-1040, PD184352 and ARRY-142886), and PI3K signaling is disrupted by CCI-779. WX-G250 targets the G250 antigen, and PS-341 disrupts the 26S proteasome mediating the degradation of intracellular proteins. Given that multiple pathways contribute to tumor growth, anti-tumor activity may be increased by agents targeting multiple pathways, or by combining agents to allow horizontal or vertical inhibition of multiple pathways.


Subject(s)
Antineoplastic Agents/therapeutic use , Benzimidazoles/therapeutic use , Carcinoma, Renal Cell/drug therapy , Drug Delivery Systems , Kidney Neoplasms/drug therapy , Angiogenesis Inhibitors/therapeutic use , Antineoplastic Agents/administration & dosage , Benzimidazoles/administration & dosage , Carcinoma, Renal Cell/pathology , Cell Proliferation/drug effects , Clinical Trials as Topic , Humans , Kidney Neoplasms/pathology , von Hippel-Lindau Disease/genetics
14.
Urologe A ; 43(10): 1271-4, 2004 Oct.
Article in German | MEDLINE | ID: mdl-15372156

ABSTRACT

Therapy of metastasized renal cell carcinoma is based on systemic immunotherapeutic strategies, if surgical resection is not possible. The costs of inhalative Interleukin-2 therapy in case of pulmonary metastases as off-label-use are not accepted by compulsory health insurance yet.We report on a female patient with pulmonary metastasized renal cell carcinoma who had tumor progression after immunochemotherapy that followed complete response after inhalative therapy with Interleukin-2.


Subject(s)
Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/secondary , Interleukin-2/administration & dosage , Kidney Neoplasms/drug therapy , Lung Neoplasms/drug therapy , Lung Neoplasms/secondary , Administration, Inhalation , Adult , Antineoplastic Agents/administration & dosage , Carcinoma, Renal Cell/diagnosis , Carcinoma, Renal Cell/therapy , Female , Humans , Immunotherapy/methods , Kidney Neoplasms/diagnosis , Lung Neoplasms/diagnosis , Lung Neoplasms/therapy , Remission Induction/methods , Treatment Failure , Treatment Outcome
15.
J Clin Oncol ; 22(7): 1188-94, 2004 Apr 01.
Article in English | MEDLINE | ID: mdl-14981107

ABSTRACT

PURPOSE: We conducted a prospectively randomized clinical trial to compare the efficacy of three outpatient therapy regimens in 341 patients with progressive metastatic renal cell carcinoma. PATIENTS AND METHODS: Patients were stratified according to known clinical predictors and were subsequently randomly assigned. Treatment arms were: arm A (n = 132), subcutaneous interferon alfa-2a (sc-IFN-alpha-2a), subcutaneous interleukin-2 (sc-IL-2), and intravenous (IV) fluorouracil; arm B (n = 146): arm A treatment combined with per oral 13-cis-retinoic acid; and arm C (n = 63), sc-IFN-alpha-2a and IV vinblastine. RESULTS: Treatment (according to the standard 8-week Hannover Atzpodien regimen) arms A, B, and C yielded objective response rates of 31%, 26%, and 20%, respectively. Arm B, but not arm A, showed a significantly improved progression-free survival (PFS) compared with arm C (P =.0248). Both arm A (median overall survival, 25 months; P =.0440) and arm B (median overall survival, 27 months; P =.0227) led to significantly improved overall survival (OS) compared with arm C (median OS, 16 months). All three sc-IFN-alpha-2a-based therapies were moderately or well tolerated. CONCLUSION: Our results established the safety and improved long-term therapeutic efficacy of sc-IL-2 plus sc-INF-alpha-2a-based outpatient immunochemotherapies, compared with sc-INF-alpha-2a/IV vinblastine.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Renal Cell/drug therapy , Immunotherapy , Kidney Neoplasms/drug therapy , Adult , Aged , Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/secondary , Disease-Free Survival , Female , Fluorouracil/administration & dosage , Humans , Infusions, Intravenous , Injections, Subcutaneous , Interferon alpha-2 , Interferon-alpha/administration & dosage , Interleukin-2/administration & dosage , Isotretinoin/administration & dosage , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Male , Middle Aged , Prospective Studies , Recombinant Proteins , Survival Rate , Treatment Outcome , Vinblastine/administration & dosage
16.
MMW Fortschr Med ; 145(22): 37-9, 2003 May 29.
Article in German | MEDLINE | ID: mdl-12866275

ABSTRACT

Urogenital infections may often have a major effect on fertility. For the most part, however, the pathogenetic aspects of such cases have not yet been clarified. In the future, the integration of functional and molecular parameters will be decisive for defining an interaction between urogenital infection and male fertility. As a rule, infection-related alterations to the ejaculate require antimicrobial treatment, although the effect of the latter on fertility remains uncertain.


Subject(s)
Infertility, Male/etiology , Anti-Bacterial Agents/therapeutic use , Epididymitis/complications , Epididymitis/diagnosis , Epididymitis/therapy , Humans , Infertility, Male/diagnosis , Infertility, Male/therapy , Male , Orchitis/complications , Orchitis/diagnosis , Orchitis/therapy , Prostatitis/complications , Prostatitis/diagnosis , Prostatitis/therapy , Urethritis/complications , Urethritis/diagnosis , Urethritis/therapy
17.
BJU Int ; 92(3): 319-22, 2003 Aug.
Article in English | MEDLINE | ID: mdl-12887491

ABSTRACT

OBJECTIVE: To compare the haemostatic properties of standard transurethral resection of the prostate (TURP) and transurethral vaporization resection of the prostate (TUVRP), as perioperative bleeding is still regarded as the major complication of prostate resection. MATERIALS AND METHODS: Isolated blood-perfused porcine kidneys were used to determine the haemostatic efficacy of TURP and TUVRP (using two different electrodes). Bleeding was quantified precisely in relation to tissue ablation for the two techniques, and specimens were evaluated histologically. RESULTS: Both TUVRP groups had significantly less bleeding (P = 0.005) than the TURP group for a standardized ablation volume of perfused kidney tissue (18.9, 19.5 and 24.1 mL/min, respectively). The different TUVRP electrodes had no significant haemostatic differences. The histology showed significantly (P = 0.03) larger coagulation zones for the TUVRP groups than for standard TURP. CONCLUSIONS: TUVRP ex-vivo was associated with significantly better haemostasis than TURP. The haemostatic properties of different active electrodes for TUVRP seem to be equivalent.


Subject(s)
Blood Loss, Surgical/prevention & control , Catheter Ablation/methods , Prostatectomy/methods , Prostatic Hyperplasia/surgery , Animals , Hemostasis, Surgical/methods , Male , Models, Biological , Swine , Transurethral Resection of Prostate/methods
18.
Ann Oncol ; 13(11): 1799-805, 2002 Nov.
Article in English | MEDLINE | ID: mdl-12419754

ABSTRACT

BACKGROUND: Peginterferon-alpha 2a (40 kDa), PEGASYS(TM) (PEG-IFN), is a modified form of recombinant human interferon (IFN)-alpha 2a with sustained absorption and prolonged half-life after subcutaneous administration. A phase II trial was conducted in previously untreated patients with advanced renal cell carcinoma (RCC) to assess efficacy, toxicity and pharmacokinetic profile. PATIENTS AND METHODS: Forty previously untreated patients with advanced RCC were enrolled on this multicenter trial. The median age was 60 years and 63% had prior nephrectomy. PEG-IFN was administered at a dose of 450 micro g/week on a weekly basis by subcutaneous injection. Serial venous blood samples were drawn to assess concentrations of PEG-IFN. RESULTS: Five (13%) patients achieved a major response (four partial and one complete). The median time to progression was 3.8 months, and 63% of patients were alive at 1 year. The toxicity profile was mostly mild to moderate in intensity. Toxicity higher than grade 2 included neutropenia (six patients), fatigue/asthenia (four patients), nausea/vomiting (three patients) and elevated hepatic transaminase concentrations (four patients). Serum drug levels were studied in all patients; mean C(max) at week 1 was 19 ng/ml, and levels were sustained at close to peak over 1 week. With chronic dosing, drug concentration was increased 3-fold, and steady state was achieved in 5-9 weeks. CONCLUSIONS: The sustained maintenance of serum levels of PEG-IFN allows once-weekly dosing. The efficacy and tolerability profile was qualitatively similar to standard IFN-alpha, and adverse events were mostly mild to moderate in nature.


Subject(s)
Carcinoma, Renal Cell/blood , Carcinoma, Renal Cell/drug therapy , Interferon-alpha/administration & dosage , Interferon-alpha/pharmacokinetics , Kidney Neoplasms/blood , Kidney Neoplasms/drug therapy , Neoplasm Invasiveness/pathology , 2',5'-Oligoadenylate Synthetase/blood , Aged , Biological Availability , Biopsy, Needle , Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/surgery , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Follow-Up Studies , Half-Life , Humans , Injections, Subcutaneous , Interferon alpha-2 , Interferon-alpha/toxicity , Kidney Function Tests , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Kidney Neoplasms/surgery , Male , Middle Aged , Neoplasm Staging , Neopterin/blood , Nephrectomy/methods , Recombinant Proteins , Risk Assessment , Survival Rate , Treatment Outcome
19.
Urologe A ; 41(5): 482-8, 2002 Sep.
Article in German | MEDLINE | ID: mdl-12426867

ABSTRACT

Brain metastases (BM) indicate an advanced stage of renal cell cancer (RCC). They pose an increasing challenge to urologists as a result of improved survival due to modern therapy. Median survival of untreated patients with BM who often suffer from neurological deficits is 3 months. Radiosurgery with the Gamma Knife (GK) has increased in use as an alternative to whole brain radiation therapy (WBRT) and/or surgery. This study reports the results of a consecutive series of RCC patients treated for BM by GK radiosurgery during a 5-year period. Between 1994 and 1999, 58 patients with a total of 277 BM and 3.0 (1-19) BM/patient were treated. Because of recurrent BM, 23 (40%) patients received repeated (multiple) GK sessions. The median tumor volume was 3.4 cm3 (0.1-19.1). The median interval between diagnosis of RCC and GK treatment was 2.2 years (0.1-17.2). Symptomatic side effects were detected in 9 (16%) of 58 patients. The median actuarial survival time was 9.9 months. Local tumor control could be achieved in 95% of patients. The GK therapy induced a significant tumor remission accompanied by rapid neurological improvement in 70% of patients. Compared to standard radiotherapy, GK radiosurgery is more effective, less time consuming, and can be repeated. Compared to surgery, radiosurgery is less invasive and better suited to treat multiple metastases in one single session. Surgery and radiosurgery, however, are supplementary methods that are highly effective to control intracerebral metastasizing RCC.


Subject(s)
Ambulatory Surgical Procedures , Brain Neoplasms/secondary , Carcinoma, Renal Cell/secondary , Kidney Neoplasms/surgery , Radiosurgery , Actuarial Analysis , Adult , Aged , Brain Neoplasms/mortality , Brain Neoplasms/pathology , Brain Neoplasms/surgery , Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/surgery , Female , Follow-Up Studies , Humans , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/surgery , Neoplasm Staging , Reoperation , Survival Rate
20.
Urology ; 58(6): 1070-3, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11744497

ABSTRACT

OBJECTIVES: To evaluate whether a laparoscopic hydro-jet device can provide a safe and effective partial nephrectomy. Partial nephrectomy is still one of the most challenging operations in urologic laparoscopy. The control of hemorrhage is very difficult to achieve with laparoscopic techniques. In open surgery, hydro-jet resection is used to cut the renal parenchyma selectively, avoiding damage to the vascular structures or collecting system.Methods. Laparoscopic wedge, as well as pole, resections of the kidney were performed in 5 pigs under general anesthesia. After exposure of the kidney, the renal capsule was incised using electrocautery. The hydro-jet was then used to dissect the renal parenchyma. In pole resections, the collecting system and central vessels were divided using an Endo-GIA. Hemostasis was achieved by electrocoagulation or clips. The dissection time and intraoperative complications were evaluated.Results. The operations were performed successfully in all animals without temporary ischemia. The hydro-jet generator allowed precise and effective tissue dissection without significant hemorrhage. The parenchymal vessels were selectively coagulated. The collecting system and central vessels remained intact and could be divided after application of the Endo-GIA. The mean dissection time was 42 +/- 6 minutes for the wedge resections and 54 +/- 8 minutes for the pole resections. CONCLUSIONS: These experimental results demonstrate the suitability of hydro-jet dissection for safe laparoscopic partial nephrectomy without temporary ischemia and with reduction of the operative trauma to the kidney. On the basis of our own experiences with other techniques, including electrocautery and laser technology for partial nephrectomy, we conclude that laparoscopic hydro-jet resection represents an interesting alternative to other techniques.


Subject(s)
Laparoscopy , Models, Animal , Nephrectomy/methods , Animals , Nephrectomy/instrumentation , Random Allocation , Swine
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