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1.
Ann Oncol ; 30(11): 1697-1727, 2019 11 01.
Article in English | MEDLINE | ID: mdl-31740927

ABSTRACT

BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial. OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management. DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts before voting during a consensus conference. SETTING: Online Delphi survey and consensus conference. PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus). RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these, 33 (28%) statements achieved level 1 consensus and 49 (42%) statements achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease and the evolving role of checkpoint inhibitor therapy in metastatic disease. CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time where further evidence is available to guide our approach.


Subject(s)
Consensus , Medical Oncology/standards , Practice Guidelines as Topic , Urinary Bladder Neoplasms/therapy , Urology/standards , Delphi Technique , Europe , Humans , International Cooperation , Medical Oncology/methods , Neoplasm Staging , Societies, Medical/standards , Stakeholder Participation , Surveys and Questionnaires , Urinary Bladder/pathology , Urinary Bladder Neoplasms/pathology , Urology/methods
2.
Ann Oncol ; 29(8): 1658-1686, 2018 08 01.
Article in English | MEDLINE | ID: mdl-30113631

ABSTRACT

The European Society for Medical Oncology (ESMO) consensus conference on testicular cancer was held on 3-5 November 2016 in Paris, France. The conference included a multidisciplinary panel of 36 leading experts in the diagnosis and treatment of testicular cancer (34 panel members attended the conference; an additional two panel members [CB and K-PD] participated in all preparatory work and subsequent manuscript development). The aim of the conference was to develop detailed recommendations on topics relating to testicular cancer that are not covered in detail in the current ESMO Clinical Practice Guidelines (CPGs) and where the available level of evidence is insufficient. The main topics identified for discussion related to: (1) diagnostic work-up and patient assessment; (2) stage I disease; (3) stage II-III disease; (4) post-chemotherapy surgery, salvage chemotherapy, salvage and desperation surgery and special topics; and (5) survivorship and follow-up schemes. The experts addressed questions relating to one of the five topics within five working groups. Relevant scientific literature was reviewed in advance. Recommendations were developed by the working groups and then presented to the entire panel. A consensus vote was obtained following whole-panel discussions, and the consensus recommendations were then further developed in post-meeting discussions in written form. This manuscript presents the results of the expert panel discussions, including the consensus recommendations and a summary of evidence supporting each recommendation. All participants approved the final manuscript.


Subject(s)
Medical Oncology/standards , Neoplasm Recurrence, Local/prevention & control , Neoplasms, Germ Cell and Embryonal/therapy , Practice Guidelines as Topic , Testicular Neoplasms/therapy , Aftercare/methods , Aftercare/standards , Cancer Survivors/psychology , Chemoradiotherapy, Adjuvant/methods , Chemoradiotherapy, Adjuvant/standards , Consensus Development Conferences as Topic , Europe , Humans , Male , Medical Oncology/methods , Neoadjuvant Therapy/methods , Neoadjuvant Therapy/standards , Neoplasm Recurrence, Local/epidemiology , Neoplasm Staging , Neoplasms, Germ Cell and Embryonal/diagnosis , Neoplasms, Germ Cell and Embryonal/pathology , Orchiectomy/psychology , Palliative Care/methods , Palliative Care/standards , Prognosis , Quality of Life , Risk Factors , Salvage Therapy/methods , Salvage Therapy/standards , Societies, Medical/standards , Survivorship , Testicular Neoplasms/diagnosis , Testicular Neoplasms/pathology , Testis/diagnostic imaging , Testis/pathology , Testis/surgery
3.
Prostate Cancer Prostatic Dis ; 20(3): 289-293, 2017 09.
Article in English | MEDLINE | ID: mdl-28244493

ABSTRACT

BACKGROUND: The imaging response to radium-223 therapy is at present poorly described. We aimed to describe the imaging response to radium-223 treatment. METHODS: We retrospectively evaluated the computed tomography (CT) and bone scintigraphy response of metastatic castration-resistant prostate cancer (CRPC) patients treated with radium-223, in eight centers in three countries. RESULTS: A total of 130 patients were included, the majority (n=84, 65%) received radium-223 post docetaxel. Thirty-four of 99 patients with available data (34%) received concomitant abiraterone or enzalutamide. A total of 54% (n=70) patients completed the planned six injections of radium-223. In patients with available data, a transient increase in bone metastases-related pain was observed in 27% (n=33/124) and an improvement of bone metastases-related pain on treatment with radium-223 was noted in 49% of patients (n=61/124). At 3 and 6 months of treatment with radium-223, bone imaging showed stable disease in 74% (n=84/113) and 94% of patients (n=93/99) with available data, respectively. An increase in the number of bone lesions was documented at 3 months compared with baseline in 26% (n=29/113) and at 6 months compared with 3 months in 6% of patients (n=6/99), respectively. Radiological extraskeletal disease progression occurred in 46% of patients (n=57/124) with available CT data at 3 and/or 6 months. CONCLUSIONS: Progression of bone metastases during radium-223 therapy is uncommon. A bone flare (pain and/or radiological) may be noted during the first 3 months, and should not be confused with progression. Imaging by CT scan should be considered after three and six doses of radium-223 to rule out extraskeletal disease progression.


Subject(s)
Bone Neoplasms/radiotherapy , Prostatic Neoplasms, Castration-Resistant/radiotherapy , Radiopharmaceuticals/therapeutic use , Radium/therapeutic use , Aged , Aged, 80 and over , Bone Neoplasms/diagnostic imaging , Bone Neoplasms/secondary , Humans , Kallikreins/blood , Male , Middle Aged , Prostate-Specific Antigen/blood , Prostatic Neoplasms, Castration-Resistant/diagnostic imaging , Prostatic Neoplasms, Castration-Resistant/pathology , Retrospective Studies , Treatment Outcome
4.
Ann Oncol ; 27(2): 324-32, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26646758

ABSTRACT

BACKGROUND: Patients with advanced, incurable cancer receiving anticancer treatment often experience multidimensional symptoms. We hypothesize that real-time monitoring of both symptoms and clinical syndromes will improve symptom management by oncologists and patient outcomes. PATIENTS AND METHODS: In this prospective multicenter cluster-randomized phase-III trial, patients with incurable, symptomatic, solid tumors, who received new outpatient chemotherapy with palliative intention, were eligible. Immediately before the weekly oncologists' visit, patients completed the palm-based E-MOSAIC assessment (Edmonton-Symptom-Assessment-Scale, ≤3 additional symptoms, estimated nutritional intake, body weight change, Karnofsky Performance Status, medications for pain, fatigue, nutrition). A cumulative, longitudinal monitoring sheet (LoMoS) was printed immediately. Eligible experienced oncologists were defined as one cluster each and randomized to receive the immediate print-out LoMoS (intervention) or not (control). Primary analysis limited to patients having uninterrupted (>4/6 visits with same oncologist) patient-oncologist sequences was a mixed model for the difference in patients global quality of life (G-QoL; items 29/30 of EORTC-QlQ-c30) between baseline (BL) and week 6. Intention-to-treat (ITT) analysis included all eligible patients. RESULTS: In 8 centers, 82 oncologists treated 264 patients (median 66 years; overall survival intervention 6.3, control 5.4 months) with various tumors. The between-arm difference in G-QoL of 102 uninterrupted patients (intervention: 55; control: 47) was 6.8 (P = 0.11) in favor of the intervention; in a sensitivity analysis (oncologists treating ≥2 patients; 50, 39), it was 9.0 (P = 0.07). ITT analysis revealed improvement in symptoms (difference last study visit-BL: intervention -5.4 versus control 2.1, P = 0.003) and favored the intervention for communication and coping. More patients with high symptom load received immediate symptom management (chart review, nurse-patient interview) by oncologists getting the LoMoS. CONCLUSION: Monitoring of patient symptoms, clinical syndromes and their management clearly reduced patients' symptoms, but not QoL. Our results encourage the implementation of real-time monitoring in the routine workflow of oncologist with a computer solution.


Subject(s)
Monitoring, Ambulatory/methods , Neoplasms/pathology , Palliative Care/methods , Symptom Assessment/methods , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Clinical Decision-Making , Female , Humans , Male , Middle Aged , Neoplasms/therapy , Outpatients , Prospective Studies , Quality of Life , Surveys and Questionnaires
5.
Ann Oncol ; 26(9): 1865-1870, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26037797

ABSTRACT

BACKGROUND: Following inguinal orchidectomy, management options for patients with stage I seminoma include initial surveillance or treatment with adjuvant radiotherapy or chemotherapy. The anticipated relapse rate for patients followed by surveillance alone is ∼15%, with adjuvant treatment this risk is reduced to ∼4%-5% at 5 years. After carboplatin treatment, follow-up strategies vary and there are no validated, predictive markers of relapse. PATIENTS AND METHODS: We conducted a retrospective analysis of all patients presenting with stage I seminoma who received a single cycle of adjuvant carboplatin in South Central England between 1996 and 2013. We report on outcome and the results of univariate and multivariate analysis evaluating possible risk factors for post carboplatin relapse. RESULTS: A total of 517 eligible patients were identified. All underwent nuclear medicine estimation of glomerular filtration rate before treatment with carboplatin (dosed at area under the curve × 7). With a median follow-up of 47.2 months (range 0.4-214 months), 21/517 patients have relapsed resulting in a 5-year estimated relapse-free survival of 95.0% (95% confidence interval 92.8% to 97.3%). Median time to relapse was 22.7 months (range 12.5-109.5 months). Relapse beyond 3 years was rare (4/517; 0.8%). Twenty of 21 (95%) relapsed patients had retroperitoneal lymph node metastases. The majority (16/21; 76%) of patients had elevated tumour markers at relapse. Twenty of 517 (3.9%) patients developed a new contralateral testicular germ-cell cancer. There were no seminoma-related deaths. Tumour size was the only variable significantly associated with an increased risk of relapse. CONCLUSIONS: Overall results for this large cohort of patients confirm an excellent prognosis for these patients with outcomes equivalent to those seen in prospective clinical trials. Increasing tumour size alone appears to be associated with an increased risk of post chemotherapy relapse.


Subject(s)
Antineoplastic Agents/therapeutic use , Carboplatin/therapeutic use , Neoplasm Recurrence, Local/pathology , Neoplasms, Germ Cell and Embryonal/drug therapy , Seminoma/drug therapy , Testicular Neoplasms/drug therapy , Adolescent , Adult , Aged , Chemotherapy, Adjuvant , Combined Modality Therapy , Disease-Free Survival , Humans , Lymphatic Metastasis/pathology , Male , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/radiotherapy , Neoplasm Staging , Neoplasms, Germ Cell and Embryonal/surgery , Orchiectomy , Retrospective Studies , Seminoma/surgery , Testicular Neoplasms/surgery , Treatment Outcome , Young Adult
6.
Prostate Cancer Prostatic Dis ; 18(2): 167-72, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25753371

ABSTRACT

BACKGROUND: This study was initiated to explore the impact of organic cation transporter 1 (OCT1) and multidrug and toxin extrusion transporter 1 (MATE1) genetic polymorphisms on toxicity, and clinical activity of metformin in patients with castration-resistant prostate cancer (CRPC). METHODS: The SAKK 08/09 trial included 44 patients with CRPC to receive single-agent metformin 1000 mg two times a day until disease progression or unwanted toxicity. Drug pathway-associated gene polymorphisms of OCT1 (rs622342) and MATE1 (rs2289669) were assessed. The primary objective of this study was to define the relationship between mutations in OCT1, MATE1 and progression-free survival (PFS) at 12 weeks absolute PFS and PSA response in consenting patients of SAKK 08/09. The secondary objective of this study was to analyze the association between mutations in OCT1, MATE1, metformin-related toxicity, PSA response at 12 weeks and overall survival. RESULTS: Thirty-six patients were evaluable for pharmacogenetic analysis. Homozygous carriers of the polymorphic OCT1 C-allele had no metformin-related toxicity as compared with 41.9% for any metformin-related toxicity in carriers of at least one wild-type A-allele (P=0.07). Disease progression according to RECIST (Response Evaluation Criteria In Solid Tumors) was significantly more frequent in homozygous carriers of the polymorphic OCT1 C-allele (80%) as compared with carriers of at least one wild-type A-allele (28.6%) (P=0.002). Disease progression according to RECIST was also more frequent in carriers of at least one polymorphic MATE1 A-allele (44%) as compared with homozygous carriers of the wild-type G-allele (12.5%) (P=0.07). OCT1 and MATE1 were not associated with PFS. CONCLUSIONS: The polymorphic OCT1 C-allele has been shown to be associated with less metformin-related toxicity and a higher risk of tumor progression in patients with CRPC receiving metformin as an anticancer treatment. Polymorphisms in metformin drug transporters are attractive molecular markers to serve as potential predictors of efficacy in future clinical studies.


Subject(s)
Metformin/adverse effects , Organic Cation Transport Proteins/genetics , Organic Cation Transporter 1/genetics , Prostatic Neoplasms, Castration-Resistant/genetics , Aged , Aged, 80 and over , Alleles , Disease-Free Survival , Genetic Association Studies , Genotype , Humans , Male , Middle Aged , Polymorphism, Single Nucleotide , Prostate-Specific Antigen/blood , Prostatic Neoplasms, Castration-Resistant/blood , Prostatic Neoplasms, Castration-Resistant/drug therapy
7.
Int J Surg Case Rep ; 5(12): 1117-9, 2014.
Article in English | MEDLINE | ID: mdl-25437652

ABSTRACT

INTRODUCTION: Neuroendocrine tumors of the small intestine represent about half of all small intestine neoplasms. Recurrence after surgery with curative intention is frequently observed but recurrence rate has not yet been described or analyzed sufficiently. PRESENTATION OF CASE: In this case bilocal recurrence 4 years after curative surgery of an ileocoecal neuroendocrine carcinoma was observed in a 64 year old female. Diagnosis and follow-up was carried out as proposed in current ENETS guidelines using somatostatin receptor scintigraphy for primary diagnosis and Ga-DOTATOC-PET/CT in follow-up. DISCUSSION: We can confirm that PET/CT for somatostatin receptor imaging shows good sensitivity in detecting neuroendocrine neoplasms and should be preferred for diagnostic, if available. For individual adaptation of follow-up procedures, as far as time intervals and preferred imaging methods are concerned, research on recurrence rate and long term outcome after curative surgery should be extended. CONCLUSION: Livelong follow-up after surgical resection of neuroendocrine tumors is necessary and Ga-DOTA/TOC-PET/CT should be the method of choice, if available.

8.
Br J Cancer ; 111(4): 651-9, 2014 Aug 12.
Article in English | MEDLINE | ID: mdl-25025963

ABSTRACT

BACKGROUND: Olaparib, an oral PARP inhibitor, has shown antitumour activity as monotherapy in patients with germline BRCA1/2 (gBRCA)-mutated breast and ovarian cancer. This study evaluated olaparib capsules in combination with liposomal doxorubicin (PLD) in patients with advanced solid tumours (NCT00819221). METHODS: Patients received 28-day cycles of olaparib, continuously (days 1-28) or intermittently (days 1-7), plus PLD (40 mg m(-2), day 1); seven olaparib dose cohorts (50-400 mg bid) were explored to determine the recommended dose. Assessments included safety, pharmacokinetics, pharmacodynamics and preliminary efficacy (objective response rate (ORR)). RESULTS: Of 44 patients treated (ovarian, n=28; breast, n=13; other/unknown, n=3), two experienced dose-limiting toxicities (grade 3 stomatitis and fatal pneumonia/pneumonitis (200 mg per 28-day cycle); grade 4 thrombocytopenia (400 mg per 7-day cycle)). The maximum tolerated dose was not reached using continuous olaparib 400 mg bid plus PLD. Grade ≥3 and serious AEs were reported for 27 (61%) and 12 (27%) patients, respectively. No major pharmacokinetic interference was observed between olaparib and PLD. The ORR was 33% (n=14 out of 42; complete response, n=3). A total of 13 responders had ovarian cancer: 10 were platinum-sensitive, 11 had a gBRCA mutation. CONCLUSIONS: Continuous/intermittent olaparib (up to 400 mg bid) combined with PLD (40 mg m(-2)) was generally tolerated and showed evidence of antitumour activity in ovarian cancer.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Ovarian Neoplasms/drug therapy , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics , Breast Neoplasms/metabolism , DNA Damage , Doxorubicin/administration & dosage , Doxorubicin/analogs & derivatives , Female , Histones/metabolism , Humans , Male , Maximum Tolerated Dose , Middle Aged , Ovarian Neoplasms/metabolism , Phthalazines/administration & dosage , Piperazines/administration & dosage , Polyethylene Glycols/administration & dosage , Treatment Outcome
9.
Ann Oncol ; 25(8): 1591-7, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24669017

ABSTRACT

BACKGROUND: Seminoma stage I is the most frequent testis cancer and single-dose carboplatin (AUC7) is an effective and widely used adjuvant treatment. Underdosing of carboplatin by 10% has been shown to almost double the rate of relapse and hence correct dosing based on accurate GFR measurement is crucial. The gold standard of GFR measurement with a radiolabelled isotope is expensive and not readily available. In many institutions, it is replaced by GFR estimation with the Cockcroft-Gault formula, which might lead to significant carboplatin underdosing and potentially inferior clinical outcome. METHODS: Retrospective analysis of all patients with stage I seminoma treated with adjuvant carboplatin between 1999 and 2012. All patients had serum creatinine measured and underwent GFR measurement with a radioisotope ((51)Cr EDTA or (99m)Tc DTPA), which was compared with seven standard GFR estimation formulae (Cockcroft-Gault, CKD-EPI, Jelliffe, Martin, Mayo, MDRD, Wright) and a flat dosing strategy. Bias, precision, rates of under- and overdosing of GFR estimates were compared with measured GFR. Bland-Altman plots were done. RESULTS: A total of 426 consecutive Caucasian male patients were included: median age 39 years (range 19-60 years), median measured GFR 118 ml/min (51-209), median administered carboplatin dose 1000 mg (532-1638). In comparison to isotopic GFR measurement, a relevant proportion of patients would have received ≤ 90% of carboplatin dose through the use of GFR estimation formulae: 4% using Mayo, 9% Martin, 18% Cockcroft-Gault, 24% Wright, 63% Jelliffe, 49% MDRD and 41% using CKD-EPI. The flat dosing strategy, Wright and Cockcroft-Gault formulae, showed the smallest bias with mean percentage error of +1.9, +0.4 and +2.1, respectively. CONCLUSIONS: Using Cockcroft-Gault or any other formula for GFR estimation leads to underdosing of adjuvant carboplatin in a relevant number of patients with Seminoma stage I and should not be regarded as standard of care.


Subject(s)
Antineoplastic Agents/administration & dosage , Carboplatin/administration & dosage , Glomerular Filtration Rate/drug effects , Kidney/drug effects , Seminoma/drug therapy , Testicular Neoplasms/drug therapy , Adolescent , Adult , Cohort Studies , Dose-Response Relationship, Drug , Humans , Kidney/physiology , Kidney Function Tests , Male , Middle Aged , Neoplasm Recurrence, Local/etiology , Neoplasm Staging , Retrospective Studies , Risk , Seminoma/pathology , Seminoma/physiopathology , Testicular Neoplasms/pathology , Testicular Neoplasms/physiopathology , Young Adult
10.
Internist (Berl) ; 54(10): 1262-70, 2013 Oct.
Article in German | MEDLINE | ID: mdl-23896735

ABSTRACT

The drug treatment of prostate cancer was for many years based on androgen deprivation with luteinizing hormone-releasing hormone (LHRH) analogues.This treatment still represents the standard first line treatment for advanced prostate cancer. In cases of progression to metastatic castration-resistant prostate cancer (mCRPC) further treatment options used to be limited. Only the chemotherapy drug docetaxel could demonstrate a significant overall survival benefit. Within the last few years, however, five new treatments for patients with mCRCP have achieved significant results in large phase III trials. Interestingly they have different mechanisms of action: abiraterone is a testosterone synthesis inhibitor, enzalutamide is a novel antiandrogen, cabazitaxel is a cytotoxic drug, radium-223 is a radionuclide and sipuleucel-T an immunotherapy. Further new drugs are under investigation. The integration of these new treatment options as well as an optimal sequence and combination is the main focus of current research.


Subject(s)
Androgen Antagonists/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Prostatic Neoplasms/therapy , Radiopharmaceuticals/therapeutic use , Taxoids/administration & dosage , Docetaxel , Humans , Male , Treatment Outcome
12.
Ann Oncol ; 24(4): 878-88, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23152360

ABSTRACT

In November 2011, the Third European Consensus Conference on Diagnosis and Treatment of Germ-Cell Cancer (GCC) was held in Berlin, Germany. This third conference followed similar meetings in 2003 (Essen, Germany) and 2006 (Amsterdam, The Netherlands) [Schmoll H-J, Souchon R, Krege S et al. European consensus on diagnosis and treatment of germ-cell cancer: a report of the European Germ-Cell Cancer Consensus Group (EGCCCG). Ann Oncol 2004; 15: 1377-1399; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part I. Eur Urol 2008; 53: 478-496; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part II. Eur Urol 2008; 53: 497-513]. A panel of 56 of 60 invited GCC experts from all across Europe discussed all aspects on diagnosis and treatment of GCC, with a particular focus on acute and late toxic effects as well as on survivorship issues. The panel consisted of oncologists, urologic surgeons, radiooncologists, pathologists and basic scientists, who are all actively involved in care of GCC patients. Panelists were chosen based on the publication activity in recent years. Before the meeting, panelists were asked to review the literature published since 2006 in 20 major areas concerning all aspects of diagnosis, treatment and follow-up of GCC patients, and to prepare an updated version of the previous recommendations to be discussed at the conference. In addition, ∼50 E-vote questions were drafted and presented at the conference to address the most controversial areas for a poll of expert opinions. Here, we present the main recommendations and controversies of this meeting. The votes of the panelists are added as online supplements.


Subject(s)
Neoplasms, Germ Cell and Embryonal/pathology , Neoplasms, Germ Cell and Embryonal/therapy , Europe , Follow-Up Studies , Humans , Neoplasm Metastasis , Neoplasm Staging , Neoplasms, Germ Cell and Embryonal/classification , Neoplasms, Germ Cell and Embryonal/diagnosis , Survival Rate
13.
Praxis (Bern 1994) ; 101(22): 1423-9, 2012 Oct 31.
Article in German | MEDLINE | ID: mdl-23117962

ABSTRACT

The treatment of metastatic melanoma has progressed greatly during the last two years. Nowadays melanomas can be divided into molecular subgroups, this being therapeutically relevant. Around 60% of melanomas show a BRAF mutation and can be treated with selected tyrokinase inhibitors. In addition a CTLA-4-antibody was developed which shuts off the natural immune breaking system resulting in a continuous anti-tumor reaction. Angiogenesis inhibitors have shown there importance in different phase II trials. We hope that this represents only the first step of an individualized treatment for metastatic melanoma.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Melanoma/drug therapy , Melanoma/secondary , Molecular Targeted Therapy/trends , Skin Neoplasms/drug therapy , Angiogenesis Inhibitors/adverse effects , Angiogenesis Inhibitors/therapeutic use , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , CTLA-4 Antigen/antagonists & inhibitors , Forecasting , Humans , Indoles/adverse effects , Indoles/therapeutic use , Ipilimumab , Melanoma/mortality , Molecular Targeted Therapy/adverse effects , Skin Neoplasms/mortality , Sulfonamides/adverse effects , Sulfonamides/therapeutic use , Survival Rate , Vemurafenib
14.
Ther Umsch ; 69(10): 585-90, 2012 Oct.
Article in German | MEDLINE | ID: mdl-23026884

ABSTRACT

Over the recent years we have seen a rapid increase in published research both in the preclinical and clinical field regarding the treatment of prostate cancer. Only within the last two years the results of four positive phase III trials, all showing improved survival for patients with metastatic castration resistant prostate cancer (mCRPC), have been presented. In this article the basis of treatment of localized and advanced prostate cancer is discussed with a focus on new treatment options. Due to the rapid evolution of options an interdisciplinary management of patients with prostate cancer has become crucial in order to offer the best treatment to the patients.


Subject(s)
Prostatic Neoplasms, Castration-Resistant , Prostatic Neoplasms , Humans , Male
15.
Praxis (Bern 1994) ; 101(7): 483-7, 2012 Mar 28.
Article in German | MEDLINE | ID: mdl-22454311

ABSTRACT

The differential diagnosis of eosinophilia is broad and constitutes a major challenge for both, the general practitioner and the hematologist. Whereas in developing countries secondary eosinophilia is commonly caused by parasitic infections, in Western and European countries eosinophilia is more often associated with atopic diseases or drug-related. This case-report presents an asymptomatic patient with marked persisting eosinophilia caused by Strongyloidiasis in whom parasitic stool examinations were repeatedly negative and infection could only be established by serologic testing.


Subject(s)
Eosinophilia/etiology , Strongyloidiasis/diagnosis , Adult , Algorithms , Chronic Disease , Diagnosis, Differential , Eosinophils , Humans , Leukocyte Count , Male
16.
Ann Oncol ; 23(2): 531-6, 2012 Feb.
Article in English | MEDLINE | ID: mdl-21527587

ABSTRACT

BACKGROUND: Oral temozolomide has shown similar efficacy to dacarbazine in phase III trials with median progression-free survival (PFS) of 2.1 months. Bevacizumab has an inhibitory effect on the proliferation of melanoma and sprouting endothelial cells. We evaluated the addition of bevacizumab to temozolomide to improve efficacy in stage IV melanoma. PATIENTS AND METHODS: Previously untreated metastatic melanoma patients with Eastern Cooperative Oncology Group performance status of two or more were treated with temozolomide 150 mg/m(2) days 1-7 orally and bevacizumab 10 mg/kg body weight i.v. day 1 every 2 weeks until disease progression or unacceptable toxicity. The primary end point was disease stabilisation rate [complete response (CR), partial response (PR) or stable disease (SD)] at week 12 (DSR12); secondary end points were best overall response, PFS, overall survival (OS) and adverse events. RESULTS: Sixty-two patients (median age 59 years) enrolled at nine Swiss centres. DSR12 was 52% (PR: 10 patients and SD: 22 patients). Confirmed overall response rate was 16.1% (CR: 1 patient and PR: 9 patients). Median PFS and OS were 4.2 and 9.6 months. OS (12.0 versus 9.2 months; P = 0.014) was higher in BRAF V600E wild-type patients. CONCLUSIONS: The primary end point was surpassed showing promising activity of this bevacizumab/temozolomide combination with a favourable toxicity profile. Response and OS were significantly higher in BRAF wild-type patients.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Melanoma/drug therapy , Skin Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/administration & dosage , Bevacizumab , Dacarbazine/administration & dosage , Dacarbazine/analogs & derivatives , Female , Humans , Male , Melanoma/secondary , Middle Aged , Skin Neoplasms/secondary , Temozolomide
17.
Swiss Med Wkly ; 141: w13243, 2011.
Article in English | MEDLINE | ID: mdl-21805405

ABSTRACT

Systemic treatment with bevacizumab is associated with increased rates of arterial and venous thromboembolism and haemorrhage. In order to investigate the pathophysiological mechanism involved, platelet adhesive and aggregatory functions were tested with a platelet function analyser (PFA-100®) in an in vitro study and in a longitudinal clinical observation study. For the in vitro study, blood from ten healthy volunteers was incubated with different concentrations of bevacizumab (0-1000 µg/ml plasma) and vascular endothelial growth factor (0-500 µg/ml). In the clinical observation study, PFA-100® closure times (CTs) and soluble P-selectin (sP-selectin) serum levels as a serological marker of platelet activation were assessed in 20 patients with metastatic cancer who were treated with bevacizumab in addition to cytotoxic chemotherapy. No significant changes of PFA-100® CTs were observed in the in vitro study. In the clinical observation study, mean PFA-100® CTs after treatment with bevacizumab were unchanged. sP-selectin was decreased after bevacizumab infusion by 18% (p = 0.045), which could suggest an inhibitory action on platelets. Our data do not support the view that increased platelet activation or increased platelet adhesiveness and aggregation by bevacizumab are relevant mechanisms for thrombus formation in clinical practice.


Subject(s)
Angiogenesis Inhibitors/pharmacology , Antibodies, Monoclonal, Humanized/pharmacology , Platelet Adhesiveness/drug effects , Platelet Aggregation/drug effects , Adult , Aged , Aged, 80 and over , Antigens/blood , Antigens/immunology , Bevacizumab , Cells, Cultured , Female , Humans , Male , Middle Aged , P-Selectin/blood , Platelet Function Tests , Vascular Endothelial Growth Factor A/pharmacology , von Willebrand Factor/immunology
19.
Urologe A ; 50(7): 830-5, 2011 Jul.
Article in German | MEDLINE | ID: mdl-21503662

ABSTRACT

BACKGROUND: Clear treatment recommendations for patients with testicular cancer exist and their stringent application has led to significant improvements in remission and survival rates. Moreover, active surveillance has become a cornerstone in the management of clinical stage I seminomatous and nonseminomatous germ cell tumors. On the other hand, the existing recommendations for the follow-up of testis cancer patients differ widely and have been changed frequently in recent years. MATERIAL AND METHODS: Follow-up recommendations in this young patient population have to be as evidence-based as possible, feasible in order to ensure adherence, and should not be harmful. Primarily, attention has to be paid to the negative impact of unnecessary radiation exposure. RESULTS: Recently, new evidence has become available regarding the relapse pattern of different disease stages of testicular cancer, the use of imaging at follow-up, and the risks of excessive radiation due to imaging, in particular that of CT scans. An interdisciplinary multinational working group consisting of urologists, medical oncologists, and radiation oncologists has reviewed and discussed the current evidence and on this basis formulated new recommendations for patients with germ cell tumors of the testis.


Subject(s)
Cooperative Behavior , Evidence-Based Medicine , Interdisciplinary Communication , Neoplasms, Germ Cell and Embryonal/therapy , Seminoma/radiotherapy , Seminoma/surgery , Testicular Neoplasms/radiotherapy , Testicular Neoplasms/surgery , Adult , Chemotherapy, Adjuvant , Combined Modality Therapy , Diagnostic Imaging , Follow-Up Studies , Humans , Lymphatic Metastasis/pathology , Male , Neoplasm Invasiveness , Neoplasm Staging , Neoplasms, Germ Cell and Embryonal/mortality , Neoplasms, Germ Cell and Embryonal/pathology , Neoplasms, Germ Cell and Embryonal/secondary , Orchiectomy , Radiotherapy Dosage , Radiotherapy, Adjuvant , Retroperitoneal Neoplasms/mortality , Retroperitoneal Neoplasms/pathology , Retroperitoneal Neoplasms/secondary , Seminoma/mortality , Seminoma/pathology , Sensitivity and Specificity , Testicular Neoplasms/mortality , Testicular Neoplasms/pathology , Tomography, X-Ray Computed
20.
Praxis (Bern 1994) ; 100(2): 91-7, 2011 Jan 19.
Article in German | MEDLINE | ID: mdl-21249635

ABSTRACT

Prostate cancer remains by far the most common malignant disease in male patients. Despite this fact, research in prostate cancer was limited for many years. Radical prostatectomy or external beam radiation for local treatment and androgen deprivation for advanced and metastatic treatment were perceived to be the only options. Over recent years however, knowledge about the disease has rapidly risen in many fields including epidemiology, prophylaxis, screening and treatment of localised and advanced disease. At the same time, obviously many new questions have arisen. The treatment of prostate cancer is currently undergoing great changes. This article summarises current treatment concepts and treatment possibilities for the near future.


Subject(s)
Prostatectomy , Prostatic Neoplasms , Humans , Male
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