Christoph Seidel

Publications

• 4.12

  Impact points

  Progression free survival of first line vascular endothelial growth factor-targeted therapy is an important prognostic parameter in patients with metastatic renal cell carcinoma.

  Christoph Seidel, Jonas Busch, Steffen Weikert, Sandra Steffens, Martin Fenner, Arnold Ganser, Viktor Grünwald

  European journal of cancer (Oxford, England : 1990). 03/2012;

  PURPOSE: Intrinsic resistance in metastatic renal cell carcinoma (mRCC) was recently associated with poor overall survival (OS), suggesting that VEGF inhibitor sensitivity may represent a valuable prognostic marker. We explored the duration of progression free survival (PFS) in first-line treatment ... [more] PURPOSE: Intrinsic resistance in metastatic renal cell carcinoma (mRCC) was recently associated with poor overall survival (OS), suggesting that VEGF inhibitor sensitivity may represent a valuable prognostic marker. We explored the duration of progression free survival (PFS) in first-line treatment and other variables as prognostic markers in mRCC. METHODS: Medical records from 119 mRCC patients receiving first line treatment with tyrosine kinase inhibitors (TKI) were retrieved retrospectively. Kaplan-Meier and log-rank analyses were employed on PFS and OS and multivariate Cox proportional hazard model analysed clinical parameters for their prognostic relevance. RESULTS: The median PFS of first line treatment was 8.4months (95% confidence interval 5.8-11) associated with a median OS of 28.2months (95% CI 20.9-35.4). Second line therapy with another TKI or mTOR-inhibitor was applied to 81 patients (68%). PFS of any second line therapy was 5.1 and 3.7months in first line treatment responders and non-responders (p=0.3), respectively. Univariate analyses revealed bone metastases, prior cytokine treatment, Memorial Sloan Kettering cancer centre (MSKCC) score, objective response rate, Eastern Cooperative Oncology Group (ECOG) performance status, first line PFS with 6months taken as cut-off parameter and second line treatment as prognostic variables. Multivariate analyses proved first line PFS above 6months (95% CI 0.154-0.641; HR 0.314), second line treatment (95% CI 0.162-0.657; HR 0.326), MSKCC score (95% CI 1.07-3.392; HR 1.905) and objective response rate (95% CI 0.358-0.989; HR 0.595) to be independent prognostic markers. CONCLUSIONS: The duration of first line PFS is an independent prognostic variable but not predictive for subsequent therapy.
• 4.35

  Impact points

  Treatment of everolimus-resistant metastatic renal cell carcinoma with VEGF-targeted therapies.

  V Grünwald, C Seidel, M Fenner, A Ganser, J Busch, S Weikert

  British journal of cancer. 11/2011; 105(11):1635-9.

  Treatment of everolimus-resistant disease remains largely undefined in metastatic renal cell carcinoma (mRCC). We report on 40 patients (pts) who receive systemic treatment after failure of everolimus. Forty pts received sunitinib (n=19), sorafenib (n=8), dovitinib (n=10) or bevacizumab/interferon (... [more] Treatment of everolimus-resistant disease remains largely undefined in metastatic renal cell carcinoma (mRCC). We report on 40 patients (pts) who receive systemic treatment after failure of everolimus. Forty pts received sunitinib (n=19), sorafenib (n=8), dovitinib (n=10) or bevacizumab/interferon (n=3) after failure of everolimus. Median progression-free survival (PFS), overall survival (OS) and best tumour response (according to Response Evaluation Criteria In Solid Tumors) were analysed retrospectively. Kaplan-Meier, log-rank test and Cox regression analyses were used to estimate or predict OS and PFS. Treatment of everolimus-resistant disease was associated with a PFS of 5.5 months. (range 0.4-22.3) and an objective partial remission (PR) in 4 pts (10%) and stable disease (SD) in 22 pts (55%). In univariate analyses, first-line treatment with sorafenib was the only variable to correlate with a prolonged PFS of treatment in everolimus-resistant disease (P=0.036). However, its significance as a predictive marker for subsequent therapy could not be verified in multivariate analyses. Vascular endothelial growth factor targeted therapy shows promising activity in everolimus-resistant metastatic renal cancer and warrants further studies.
• 7.67

  Impact points

  Sequence therapy in patients with metastatic renal cell carcinoma: comparison of common targeted treatment options following failure of receptor tyrosine kinase inhibitors.

  Jonas Busch, Christoph Seidel, Carsten Kempkensteffen, Manfred Johannsen, Ingmar Wolff, Stefan Hinz, Ahmed Magheli, Kurt Miller, Viktor Grünwald, Steffen Weikert

  European urology. 07/2011; 60(6):1163-70.

  The best sequence of targeted therapy in patients with metastatic renal cell carcinoma (mRCC) has not been sufficiently defined. To describe the efficacy and toxicity of sequential everolimus (EV) versus receptor tyrosine kinase inhibitor (rTKI) following failure of first rTKI treatment. Retrospecti... [more] The best sequence of targeted therapy in patients with metastatic renal cell carcinoma (mRCC) has not been sufficiently defined. To describe the efficacy and toxicity of sequential everolimus (EV) versus receptor tyrosine kinase inhibitor (rTKI) following failure of first rTKI treatment. Retrospective study of 108 patients receiving rTKI or EV after progression on rTKI therapy at two German academic centres. Sequence of systemic targeted treatment with sunitinib (n=85) or sorafenib (n=23) followed by EV (n=62) or another rTKI (n=46; sorafenib, n=35; sunitinib, n=11). We measured response rate (Response Evaluation Criteria in Solid Tumours 1.0) and toxicity. Survival analysis (Kaplan-Meier method and Cox regression) was conducted for progression-free survival (PFS) and overall survival (OS). Main patient characteristics did not significantly differ by sequence of treatment groups (rTKI-rTKI vs rTKI-EV). Response rate following first rTKI failure was not significantly different between sequential therapies with a disease control rate of 51.6% (EV) and 43.5% (rTKI). The corresponding median PFS was 3.6 mo (95% confidence interval [CI], 1.8-5.4) for EV and 4.0 mo (3.2-4.9) for rTKI treatment. The estimated OS was longer for the rTKI-EV group (43 mo; 95% CI, 33.9-52.1) than for the rTKI-rTKI group (29 mo; 95% CI, 18.6-39.5; p=0.03), but this difference lost statistical significance in multivariable-adjusted analyses. Intrinsic rTKI resistance was independently associated with inferior subsequent PFS (hazard ratio [HR]: 1.79; 95% CI, 1.15-3.62; p=0.015) and OS (HR: 6.54; 95% CI, 3.01-14.20; p<0.001). Limitations are the retrospective design, limited numbers of cases, and residual confounding factors. The sequence therapies rTKI-EV and rTKI-rTKI may be equally efficacious in terms of PFS and response rate, whereas a tendency towards superior survival was observed for the rTKI-EV sequence. These data, particularly the potential benefit of an early change of mode of action, need confirmation in randomised comparative trials.

• [Use of mTOR-inhibitors in solid tumors].

  Christoph Seidel, Viktor Grünwald

  Medizinische Monatsschrift für Pharmazeuten. 04/2011; 34(4):116-26; quiz 127-8.

  mTOR-inhibitors are part of targeted agents and are already in use in the clinic, especially for treatment of metastatic renal cell carcinoma. Distinct from conventional chemotherapeutics, targeted agents imply chronic treatment, which has changed our perspective on the commerce of adverse events (A... [more] mTOR-inhibitors are part of targeted agents and are already in use in the clinic, especially for treatment of metastatic renal cell carcinoma. Distinct from conventional chemotherapeutics, targeted agents imply chronic treatment, which has changed our perspective on the commerce of adverse events (AE). In principle, mTOR-inhibitors are associated with a broad number of AEs. The occurrence of stomatitis, infection, pneumonitis, hyperlipidemia and hyperglycemia are considered major class effects of mTOR-inhibitors. However, severe adverse events remain scarce among mTOR-inhibitors and support chronic use of these agents. Based on their good clinical tolerability mTOR-inhibitors are prone to be developed in combinational therapies. However, the hepatic metabolism of these agents may limit their use to partners with a distinct metabolism in order to avoid drug interaction. Meanwhile about 40 different trials use mTOR-inhibitors in different tumor entities. The use of mTOR-inhibitors in neuroendocine tumors of the intestine, mantle cell lymphoma and sarcomas has hereby shown to be very promising. The mainstay of therapy already incorporates the use of everolimus in second line and temsirolimus in first line treatment in patients with metastatic renal cell carcinoma.
• 2.63

  Impact points

  Response of renal lesions during systemic treatment with sunitinib in patients with metastatic renal cell carcinoma: a single center experience with 14 patients.

  C Seidel, M Fenner, A S Merseburger, C Reuter, P Ivanyi, F Länger, A Ganser, V Grünwald

  World journal of urology. 01/2011; 29(3):355-60.

  The tyrosine kinase inhibitor (TKI) sunitinib induces partial remissions (PR) in a substantial proportion of patients with metastatic renal cell carcinoma (mRCC). Only little is known about the activity of sunitinib in renal lesions in patients with metastatic disease, as most patients with synchron... [more] The tyrosine kinase inhibitor (TKI) sunitinib induces partial remissions (PR) in a substantial proportion of patients with metastatic renal cell carcinoma (mRCC). Only little is known about the activity of sunitinib in renal lesions in patients with metastatic disease, as most patients with synchronous metastases receive palliative nephrectomy. Fourteen patients with clear cell mRCC with renal lesions and sunitinib therapy (50 mg OD, 4/2 scheme) were retrieved retrospectively from clinic records. Tumor assessment consisted of CT scans at least every two cycles, analyzed according to RECIST. In 5 of 14 patients, renal tumors were considered as the primary tumor, while the remaining patients had kidney metastases. In total, 65 target lesions were evaluated. The median progression-free survival (PFS) of sunitinib was 8.7 months (range: 2.7-40.2). Median overall survival (OS) from initiation of TKI therapy was 26 months (range: 3-55). Best response according to RECIST consisted of partial remission (PR) in 4 patients, stable disease (SD) in 7 patients, a complete remission (CR) in 1 patient, and 2 patients with progressive disease (PD). Analyzing the response of renal lesions only, 1 patient had PD, 8 patients had SD, 4 patients had PR, and 1 had a CR. Palliative nephrectomy was performed after two courses of sunitinib in 2 patients. In our cohort, similar responses of renal tumors and peripheral metastases were achieved with sunitinib treatment. Our results support the use of sunitinib to control renal tumor lesions in metastatic patients.

• The role of diabetes mellitus in localized and metastatic renal cell carcinoma

  Sandra Steffens, Christoph von Klot, Hendrik Egggers, Christoph Seidel, Gerd Wegener, Mark Schrader, Markus A. Kuczyk, Andres J. Schrader

  Journal of Diabetes mellitus. 01/2011; Volume 01(Number 04).
• 1.23

  Impact points

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

  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) has predictive impact on the progression-free survival (PFS) and overall survival (OS) under everoli... [more] 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.
• 6.70

  Impact points

  Does obesity influence the prognosis of metastatic renal cell carcinoma in patients treated with vascular endothelial growth factor-targeted therapy?

  Sandra Steffens, Viktor Grünwald, Kristina I Ringe, Christoph Seidel, Hendrik Eggers, Mark Schrader, Frank Wacker, Markus A Kuczyk, Andres J Schrader

  The oncologist. 01/2011; 16(11):1565-71.

  Obesity increases the risk for renal cell carcinoma (RCC). However, it has only recently been identified as an independent positive prognostic factor for localized RCC. To determine whether obesity influences long-term prognosis in metastatic RCC patients receiving vascular endothelial growth factor... [more] Obesity increases the risk for renal cell carcinoma (RCC). However, it has only recently been identified as an independent positive prognostic factor for localized RCC. To determine whether obesity influences long-term prognosis in metastatic RCC patients receiving vascular endothelial growth factor-targeted therapy. In 116 patients with metastatic RCC who received antiangiogenic agents (sunitinib, sorafenib, axitinib, bevacizumab) in 2005-2010, we evaluated whether body mass index (BMI), a body surface area (BSA) above the European average, the visceral fat area (VFA), or s.c. fat area (SFA) were of predictive relevance. BMI was categorized based on current World Health Organization definitions. BSA was stratified according to the European average for men (1.98 m(2)) and women (1.74 m(2)). VFA and SFA were dichotomized using the median of the observed distribution as the cutoff. The primary endpoints of this study were time to progression and overall survival time. The whole population had median progression-free and overall survival times of 8.3 months and 20.5 months, respectively. In contrast to BMI and BSA, higher than average VFA and SFA levels were significant predictors of longer progression-free and overall survival times. The major limitations of this study are its retrospective design and its heterogeneous patient population. This is the first study to identify high VFA and SFA levels as positive predictive biomarkers for patients who receive first-line antiangiogenic agents for metastatic RCC.
• 2.74

  Impact points

  Intrinsic resistance to tyrosine kinase inhibitors is associated with poor clinical outcome in metastatic renal cell carcinoma.

  Jonas Busch, Christoph Seidel, Steffen Weikert, Ingmar Wolff, Carsten Kempkensteffen, Lisa Weinkauf, Stefan Hinz, Ahmed Magheli, Kurt Miller, Viktor Grünwald

  BMC cancer. 01/2011; 11:295.

  Data on sequential therapy in patients with metastatic renal cell carcinoma (mRCC) and intrinsic resistance to receptor tyrosine kinase inhibitor (rTKI) treatment remains vague. We retrospectively studied treatment characteristics and outcome of mRCC patients refractory to first rTKI therapy. Thirty... [more] Data on sequential therapy in patients with metastatic renal cell carcinoma (mRCC) and intrinsic resistance to receptor tyrosine kinase inhibitor (rTKI) treatment remains vague. We retrospectively studied treatment characteristics and outcome of mRCC patients refractory to first rTKI therapy. Thirty-five mRCC patients (male, 18; female, 11) with primary resistance to first rTKI therapy (sunitinib, n = 28; sorafenib, n = 7) and a median treatment interval of 2.4 months (1 - 4.6) were identified. In 22 patients, progressive disease (PD) was determined by a new metastatic lesion. Of these, 16 patients received subsequent therapy with 12 patients remaining refractory and 4 patients achieving disease stabilization. In 13 patients continuous growth of existing metastatic lesions determined PD. Of these, 9 received sequential therapy with 6 achieving disease stabilization. Altogether, 25 patients were treated sequentially (rTKI: n = 15; mTOR-inhibitor: n = 10) and achieved a median PFS of 3.2 months (range, 1-16.6). Fifteen patients failed to respond to either line of therapy. Disease control was not associated with type of subsequent therapy. Median OS was 14.9 months (CI: 5.5-24.4). Intrinsic resistance to rTKI is associated with a low chance of response to sequential therapy and a poor prognosis in mRCC patients.
• 1.23

  Impact points

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

  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, subsequent treatment in mTORi-refractory disease remains undetermined. We analyzed the efficacy of s... [more] 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.
• 5.65

  Impact points

  Recall pneumonitis during systemic treatment with sunitinib.

  C Seidel, S Janssen, J H Karstens, T Welte, M Morgan, A Ganser, V Grünwald

  Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. 10/2010; 21(10):2119-20.
• 2.87

  Impact points

  Microsatellite analysis of allelic imbalance in tumour and blood from patients with prostate cancer.

  Heidi Schwarzenbach, Felix K-H Chun, Imke Müller, Christoph Seidel, Karoline Urban, Andreas Erbersdobler, Hartwig Huland, Klaus Pantel, Martin G Friedrich

  BJU international. 07/2008; 102(2):253-8.

  OBJECTIVE: To investigate whether a high frequency of allelic imbalance (AI) is associated with clinicopathological variables of patients with prostate cancer. PATIENTS AND METHODS: We analysed loss of heterozygosity (LOH) and microsatellite (MS) instability (MSI) on circulating plasma DNA in a poly... [more] OBJECTIVE: To investigate whether a high frequency of allelic imbalance (AI) is associated with clinicopathological variables of patients with prostate cancer. PATIENTS AND METHODS: We analysed loss of heterozygosity (LOH) and microsatellite (MS) instability (MSI) on circulating plasma DNA in a polymerase chain reaction (PCR)-based MS study of 230 patients with prostate cancer and 43 with benign prostatic hyperplasia (BPH) using a panel of 13 polymorphic MS markers. RESULTS: The overall incidence of AI was significantly higher in primary tumours (34%) than in blood plasma samples from patients with prostate cancer (11%). Although LOH (2.0%) and MSI (1.5%) were also found in BPH plasma samples, their frequencies were low. AI identified in plasma samples from patients with prostate cancer could be retrieved in 63% of the paired tumour samples. The highest concordance of AI and retention of heterozygosity between tumour and plasma samples was 83% at the marker D8S360. There were high frequencies of LOH at the markers THRB, D7S522 and D8S137 in both types of specimens. The markers D11S898 and D11S1313 on the chromosome arm 11q showed frequent MSI. The comparison with established risk factors showed significant associations of an increase in prostate volume with AI at the combined markers D6S474/D7S522 in tumour tissues and at D7S522 in plasma samples (P < 0.04). In the primary tumours there was a further correlation of LOH at D11S1313 with increasing tPSA value (P = 0.005). The combination of total prostate-specific antigen (PSA) and % free PSA was associated with LOH at THRB in plasma samples. CONCLUSIONS: Plasma-based MS analysis may have clinical value for the molecular staging of prostate cancer.