Christoph Reuter

Publications of Christoph Reuter

• Integrative prognostic risk score in acute myeloid leukemia with normal karyotype.

  Authors: Frederik Damm, Michael Heuser, Michael Morgan, Katharina Wagner, Kerstin Görlich, Anika Grosshennig, Iyas Hamwi, Felicitas Thol, Ewa Surdziel, Walter Fiedler, Michael Lübbert, Lothar Kanz, Christoph Reuter, Gerhard Heil, Ruud Delwel, Bob Löwenberg, Peter J M Valk, Jürgen Krauter, Arnold Ganser

  Blood. 03/2011; 117(17):4561-8.

  To integrate available clinical and molecular information for cytogenetically normal acute myeloid leukemia (CN-AML) patients into one risk score, 275 CN-AML patients from multicenter treatmentTo integrate available clinical and molecular information for cytogenetically normal acute myeloid leukemia (CN-AML) patients into one risk score, 275 CN-AML patients from multicenter treatment trials AML SHG Hannover 0199 and 0295 and 131 patients from HOVON/SAKK protocols as external controls were evaluated for mutations/polymorphisms in NPM1, FLT3, CEBPA, MLL, NRAS, IDH1/2, and WT1. Transcript levels were quantified for BAALC, ERG, EVI1, ID1, MN1, PRAME, and WT1. Integrative prognostic risk score (IPRS) was modeled in 181 patients based on age, white blood cell count, mutation status of NPM1, FLT3-ITD, CEBPA, single nucleotide polymorphism rs16754, and expression levels of BAALC, ERG, MN1, and WT1 to represent low, intermediate, and high risk of death. Complete remission (P = .005), relapse-free survival (RFS, P < .001), and overall survival (OS, P < .001) were significantly different for the 3 risk groups. In 2 independent validation cohorts of 94 and 131 patients, the IPRS predicted different OS (P < .001) and RFS (P < .001). High-risk patients with related donors had longer OS (P = .016) and RFS (P = .026) compared with patients without related donors. In contrast, intermediate-risk group patients with related donors had shorter OS (P = .003) and RFS (P = .05). Donor availability had no impact on outcome of patients in the low-risk group. Thus, the IPRS may improve consolidation treatment stratification in CN-AML patients. Study registered at www.clinicaltrials.gov as #NCT00209833.

• Retrospective analyses of patient characteristics having predictive impact on survival under everolimus.

  Authors: Christoph Seidel, Martin Fenner, Christoph Reuter, Axel S Merseburger, Arnold Ganser, Viktor Grünwald

  Onkologie. 01/2011; 34(3):111-4.

  Everolimus is the standard second-line therapy for patients with metastatic renal cell carcinoma (mRCC). We evaluated whether the response to first-line therapy with a tyrosine kinase inhibitor (TKI)Everolimus is the standard second-line therapy for patients with metastatic renal cell carcinoma (mRCC). We evaluated whether the response to first-line therapy with a tyrosine kinase inhibitor (TKI) has predictive impact on the progression-free survival (PFS) and overall survival (OS) under everolimus. In addition, patient characteristics were evaluated for their predictive impact on the response under everolimus. 42 patients with mRCC treated with everolimus (RAD001) within a clinical trial were analyzed. Prior to everolimus, every patient had received at least 1 TKI therapy. Another TKI for second line was given to 15 patients. PFS and OS were estimated according to the Kaplan-Meier method and compared with the log-rank test. Median PFS during everolimus therapy was 5.2 months (range 1.3-17.8). 27 patients (64%) achieved stable disease (SD) or partial remission (PR). Patients with a beneficial PFS under first-line TKI achieved a better OS after start of everolimus treatment (p = 0.05) and so did TKI responders (p = 0.04). A reduced OS was associated with liver metastases (p = 0.04) and high tumor burden (p = 0.01). A beneficial outcome under prior TKI therapy is predictive for a superior survival in patients treated with everolimus, while high tumor burden and liver metastases impair the OS.

• Efficacy of sunitinib re-exposure after failure of an mTOR inhibitor in patients with metastatic RCC.

  Authors: Viktor Grünwald, Steffen Weikert, Christoph Seidel, Jonas Busch, Antje Johannsen, Martin Fenner, Christoph Reuter, Arnold Ganser, Manfred Johannsen

  Onkologie. 01/2011; 34(6):310-4.

  The sequential use of tyrosine kinase inhibitors (TKI) followed by mTOR inhibitors (mTORi) has been recently established for the systemic treatment of metastatic renal cell carcinoma (mRCC). However,The sequential use of tyrosine kinase inhibitors (TKI) followed by mTOR inhibitors (mTORi) has been recently established for the systemic treatment of metastatic renal cell carcinoma (mRCC). However, subsequent treatment in mTORi-refractory disease remains undetermined. We analyzed the efficacy of sunitinib re-challenge after failure of an mTORi at 2 German centers. Thirteen patients who failed both sunitinib and an mTORi were analyzed, and all patients were re-exposed to sunitinib. Tumor assessment was performed every 2nd cycle of sunitinib or every 3 months. Tumor response was assessed according to RECIST criteria. Initial treatment with sunitinib was associated with a median progression free survival (PFS) of 21 months. Objective response consisted of 2 (15%) complete remissions and 7 (54%) partial remissions (PR) as best response. At the time of re-exposure, 12 of 13 (92%) patients again showed clinical benefit which was associated with a median PFS of 6.9 months and consisted of 2 (15%) PR and 10 (77%) disease stabilizations. In sunitinib-responsive patients, re-challenge with sunitinib has been successfully introduced after mTORi-refractory disease, underscoring the at least partially transient nature of TKI resistance in mRCC.

• Treatment with tyrosine kinase inhibitors in patients with metastatic renal cell carcinoma is associated with drug-induced hyperparathyroidism: a single center experience in 59 patients.

  Authors: Philipp Ivanyi, Thomas Winkler, Anika Grosshennig, Christoph Reuter, Axel S Merseburger, Arnold Ganser, Viktor Grünwald

  World journal of urology. 06/2010; 28(3):311-7.

  Multi-targeted tyrosine kinase inhibitors (MTKIs) are the standard in the treatment of metastatic renal cell carcinoma (mRCC). In spite their clinical activity, interaction with physiologicalMulti-targeted tyrosine kinase inhibitors (MTKIs) are the standard in the treatment of metastatic renal cell carcinoma (mRCC). In spite their clinical activity, interaction with physiological functions has been shown. Here, we report on alterations of the bone mineral metabolism in patients with mRCC treated with MTKIs. Fifty-nine patients with mRCC treated during April 2005 and September 2009 at our center were evaluated. Demographics, chemistry, parathyroid and renal function, bone metastasis and clinics were assessed, retrospectively. Parathyroid hormone (PTH), calcium and phosphate were either determined prior to, during or after cessation of MTKI therapy. From evaluable patients, 90% (N = 53) received at least one MTKI treatment, 10% (N = 8) had evaluations without MTKI exposure. The mean PTH value prior to MTKI treatment was 49.4 (range (r):2.5-115), increased during the therapy to 121.2 (r:5-302) (P = 0.003) and returned to its basic values after MTKI cessation. In parallel, mean phosphate significantly decreased during the treatment from 1.10 (r = 0.66-1.59) to 0.87 (r = 0.48-1.45) (P < 0.001) and calcium showed a slight decrease (P = 0.039). PTH alterations were associated with clinical signs in some patients but not with bone metastasis or renal function. Univariate logistic regression analysis of pathologically elevated PTH levels revealed an association with MTKI treatment duration. Even though the mechanism of bone mineral alteration remains elusive, the MTKI treatment is associated with a dysregulated parathyroid axis, which may have clinical implications in a number of patients. Furthermore, prospective trials are mandatory, and PTH monitoring should be considered in selected patients during MTKI treatment.

• Circulating endothelial cells are an early predictor in renal cell carcinoma for tumor response to sunitinib.

  Authors: Viktor Gruenwald, Gernot Beutel, Susanne Schuch-Jantsch, Christoph Reuter, Philipp Ivanyi, Arnold Ganser, Marion Haubitz

  BMC cancer. 01/2010; 10:695.

  Tyrosine kinase inhibitors (TKI) have enriched the therapeutic options in patients with renal cell carcinoma (RCC), which frequently induce morphological changes in tumors. However, only little isTyrosine kinase inhibitors (TKI) have enriched the therapeutic options in patients with renal cell carcinoma (RCC), which frequently induce morphological changes in tumors. However, only little is known about the biological activity of TKI. Circulating endothelial cells (CEC) have been associated with endothelial damage and, hence, may serve as a putative marker for the biological activity of TKI. The main objective of our study was to evaluate the predictive value of CEC, monocytes, and soluble vascular endothelial growth factor receptor (sVEGFR)-2 in RCC patients receiving sunitinib treatment. Analyses of CEC, monocytes, and sVEGFR-2 were accomplished for twenty-six consecutive patients with metastatic RCC who received treatment with sunitinib (50 mg, 4 wks on 2 wks off schedule) at our institution in 2005 and 2006. In RCC patients CEC are elevated to 49 ± 44/ml (control 8 ± 8/ml; P = 0.0001). Treatment with sunitinib is associated with an increase in CEC within 28 days of treatment in patients with a Progression free survival (PFS) above the median to 111 ± 61 (P = 0.0109), whereas changes in patients with a PFS below the median remain insignificant 69 ± 61/ml (P = 0.1848). Monocytes and sVEGFR2 are frequently altered upon sunitinib treatment, but fail to correlate with clinical response, defined by PFS above or below the median. Sunitinib treatment is associated with an early increase of CEC in responding patients, suggesting superior endothelial cell damage in these patients as a putative predictive biomarker.

• Molecular targeted therapies for solid tumors: management of side effects.

  Authors: Viktor Grünwald, Jens Soltau, Philipp Ivanyi, Jochen Rentschler, Christoph Reuter, Joachim Drevs

  Onkologie. 04/2009; 32(3):129-38.

  This review will provide physicians and oncologists with an overview of side effects related to targeted agents that inhibit vascular endothelial growth factor (VEGF), epidermal growth factor (EGF)This review will provide physicians and oncologists with an overview of side effects related to targeted agents that inhibit vascular endothelial growth factor (VEGF), epidermal growth factor (EGF) and mammalian target of rapamycin (mTOR) signaling in the treatment of solid tumors. Such targeted agents can be divided into monoclonal antibodies, tyrosine kinase inhibitors, multitargeted tyrosine kinase inhibitors and serine/threonine kinase inhibitors. Molecular targeted therapies are generally well tolerated, but inhibitory effects on the biological function of the targets in healthy tissue can result in specific treatment-related side effects, particularly with multitargeted agents. We offer some guidance on how to manage adverse events in cancer patients based on the range of options currently available.

• Novel therapies in advanced renal cell carcinoma: management of adverse events from sorafenib and sunitinib.

  Authors: Philipp Ivanyi, Thomas Winkler, Arnold Ganser, Christoph Reuter, Viktor Grünwald

  Deutsches Ärzteblatt international. 04/2008; 105(13):232-7.

  INTRODUCTION: Sorafenib and Sunitinib are the first tyrosine kinase inhibitors licensed for the treatment of advanced renal cell carcinoma. In contrast to conventional chemotherapy, targetedINTRODUCTION: Sorafenib and Sunitinib are the first tyrosine kinase inhibitors licensed for the treatment of advanced renal cell carcinoma. In contrast to conventional chemotherapy, targeted therapies have distinct and specific side effects. METHODS: Selective review in Medline and the data base of the American Society of Clinical Oncology on the treatment and side effects of tyrosine kinase inhibitors in renal cell carcinoma, drawing on the authors' own experience. RESULTS AND DISCUSSION: Tyrosine kinase inhibitors are characterized by a variety of uncommon side effects, such as lassitude, mucosal inflammation and skin changes. The detection and treatment of adverse events are critical for interdisciplinary cancer treatment in order to ensure patients' safety. This article offers an overview of the unwanted effects of drug therapy in the management of renal cell carcinoma.

• Severe oral chronic graft-versus-host disease following allogeneic bone marrow transplantation: highly effective treatment with topical tacrolimus.

  Authors: André Eckardt, Oliver Starke, Michael Stadler, Christoph Reuter, Bernd Hertenstein

  Oral oncology. 10/2004; 40(8):811-4.

  Oral involvement of chronic graft-versus-host disease (GvHD) is a most distressing and disabling complication of hematopoietic cell transplantation, for which systemic immunosuppression as well asOral involvement of chronic graft-versus-host disease (GvHD) is a most distressing and disabling complication of hematopoietic cell transplantation, for which systemic immunosuppression as well as topical corticosteroid treatment may offer only limited symptomatic relief. Here we report encouraging preliminary results with the application of tacrolimus (FK-506) as a 0.1% ointment in three patients with severe oral chronic GvHD, heavily pretreated without success, who experienced rapid, consistent, complete or at least marked, subjective and objective improvement with topical tacrolimus.