Publications by authors named "Wolfgang Eisterer"

46 Publications

Comparison of nab-paclitaxel plus gemcitabine in elderly versus younger patients with metastatic pancreatic cancer: Analysis of a multicentre, prospective, non-interventional study.

Eur J Cancer 2021 01 6;143:101-112. Epub 2020 Dec 6.

Klinikum Klagenfurt Am Wörthersee, Internal Medicine and Oncology, Feschnigstraße 11, 9020, Klagenfurt, Austria. Electronic address:

Background: Pancreatic cancer (PC) ranks among the deadliest malignancies worldwide. In the MPACT study, first-line nab-paclitaxel plus gemcitabine (nab-P/G) demonstrated activity (median overall survival [OS], 8.7 months) and tolerability in patients with metastatic PC (mPC). However, the clinical evidence of nab-P/G in the elderly (>70 years), who account for the majority of patients with mPC, is limited. This is the first prospective, multicentre, non-interventional study evaluating the tolerability and effectiveness of nab-P/G in younger (≤70 years) versus elderly (>70 years) patients with mPC in the daily clinical routine.

Methods: Eligible patients with mPC were treated with nab-P/G and observed until disease progression or unacceptable toxicity. The primary objectives were safety and tolerability of nab-P/G, and the secondary objectives were efficacy and real-life dosing.

Results: A total of 317 patients with mPC (median age, 70 years) were recruited, of which 299, aged ≤70 (n = 162) and >70 (n = 137) years, were eligible for analysis. Baseline characteristics and the safety profile were comparable between the groups. However, fatigue (22.8% versus 13.0%) and decreased appetite (8.8% versus 1.2%) were more frequent in elderly patients. Younger versus elderly patients equally benefited in terms of objective response rate (36% versus 48%), median progression-free survival (5.6 versus 5.5 months; hazard ratio [HR] = 1.03; p = 0.81) and OS (10.6 versus 10.2 months; HR = 0.89; p = 0.4). In addition, the median treatment duration (5 versus 4 cycles), relative dose intensity (70% versus 74%) or reasons for treatment discontinuation were similar. Most patients (56.2% versus 47.4%) benefited from a second-line therapy.

Conclusion: This prospective real-world analysis confirms the feasibility and tolerability of nab-P/G treatment and reveals OS data similar for younger patients and elderly patients aged >70 years. CLINICALTRIALS.

Gov Registration: NCT02555813.

Austrian Nis Registry: NIS005071.
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January 2021

Dihydropyrimidine Dehydrogenase Testing prior to Treatment with 5-Fluorouracil, Capecitabine, and Tegafur: A Consensus Paper.

Oncol Res Treat 2020 23;43(11):628-636. Epub 2020 Oct 23.

Klinik für Innere Medizin I, Universitätsklinikum Ulm, Ulm, Germany.

Background: 5-Fluorouracil (FU) is one of the most commonly used cytostatic drugs in the systemic treatment of cancer. Treatment with FU may cause severe or life-threatening side effects and the treatment-related mortality rate is 0.2-1.0%.

Summary: Among other risk factors associated with increased toxicity, a genetic deficiency in dihydropyrimidine dehydrogenase (DPD), an enzyme responsible for the metabolism of FU, is well known. This is due to variants in the DPD gene (DPYD). Up to 9% of European patients carry a DPD gene variant that decreases enzyme activity, and DPD is completely lacking in approximately 0.5% of patients. Here we describe the clinical and genetic background and summarize recommendations for the genetic testing and tailoring of treatment with 5-FU derivatives. The statement was developed as a consensus statement organized by the German Society for Hematology and Medical Oncology in cooperation with 13 medical associations from Austria, Germany, and Switzerland. Key Messages: (i) Patients should be tested for the 4 most common genetic DPYD variants before treatment with drugs containing FU. (ii) Testing forms the basis for a differentiated, risk-adapted algorithm with recommendations for treatment with FU-containing drugs. (iii) Testing may optionally be supplemented by therapeutic drug monitoring.
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March 2021

REGO-ACT: assessment of physical activity during treatment with regorafenib for metastatic colorectal cancer.

Wien Klin Wochenschr 2020 Aug 8;132(15-16):423-430. Epub 2020 Jul 8.

Department of Internal Medicine IV, Klinikum Wels-Grieskirchen, Grieskirchnerstraße 42, 4600, Wels, Austria.

Background: A frequent side effect of the multikinase inhibitor regorafenib is fatigue. Physical activity has shown potential in reducing cancer-related fatigue.

Methods: This non-interventional pilot study assessed physical activity levels of metastatic colorectal cancer (mCRC) patients treated with regorafenib based on median daily step counts measured at 1‑week intervals using a pedometer. The study further evaluated relations between physical activity levels and fatigue, quality of life (QoL) and progression-free survival.

Results: Pedometer data were available for 22 out of 25 enrolled patients. The numbers of days with available pedometer data ranged from 6 to 100 days. The overall median daily step count was 2357 (range 10-14,931), with substantial interindividual and intraindividual variations. Interindividual median weekly step counts were in the range of 5000-7000 in some, 2000-3000 in others, and several hundreds or less in a few patients. Intraindividual daily step counts also varied by several thousands of steps. Step counts in weeks in which patients reported fatigue were well within the range of or even higher than step counts in adjacent weeks, indicating a lack of correlation. The risk of disease progression was also independent of median weekly step counts; however, significant correlations were seen between QoL and step counts.

Conclusion: Despite the severity of their disease patients showed remarkable levels of walking activity. In view of the highly individual activity levels, exercise prescriptions for seriously ill patient populations should be personalized to the specific needs and preferences of each individual patient.
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August 2020

The AST/ALT (De Ritis) ratio predicts clinical outcome in patients with pancreatic cancer treated with first-line nab-paclitaxel and gemcitabine: analysis of an Austrian multicenter, noninterventional study.

Ther Adv Med Oncol 2020 10;12:1758835919900872. Epub 2020 Apr 10.

Division of Oncology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, Graz, 8036, Austria.

Background: The pretreatment De Ritis ratio [aspartate transaminase (AST)/alanine transaminase (ALT)] has been shown to be an adverse prognostic marker in various cancer entities. However, its relevance to advanced pancreatic ductal adenocarcinoma (PDAC) has not yet been studied. In the present study we investigated the AST/ALT ratio as a possible predictor of treatment response and disease outcome in patients with advanced PDAC treated with first-line gemcitabine/nab-paclitaxel.

Methods: A analysis of a prospective, multicenter, noninterventional study was performed. A total of 202 patients with advanced PDAC treated with first-line gemcitabine/nab-paclitaxel for whom the AST/ALT ratio was measured were included in this analysis.

Results: Median and 1-year progression-free survival estimates were 4.8 months and 5.1%, respectively in patients with an AST/ALT ratio above the 75th percentile of its distribution, and 6.0 months and 18.7%, respectively in patients with an AST/ALT ratio less than or equal to this cutoff, respectively (log-rank  = 0.004). In univariable Cox regression, a doubling of the AST/ALT ratio was associated with a 1.4-fold higher relative risk of progression or death [hazard ratio = 1.38, 95% confidence interval (CI): 1.06-1.80,  = 0.017]. The prognostic association was also found in multivariable analysis adjusting for Eastern Cooperative Oncology Group performance status and lung metastases (hazard ratio per AST/ALT ratio doubling = 1.32, 95% CI: 1.00-1.75,  = 0.047). In treatment response analysis, a doubling of the AST/ALT ratio was associated with a 0.5-fold lower odds of objective response (odds ratio = 0.54, 95% CI: 0.31-0.94,  = 0.020).

Conclusions: The pretreatment serum AST/ALT ratio predicts poor disease outcome and response rate in patients with advanced PDAC treated with gemcitabine/nab-paclitaxel and might represent a novel and inexpensive marker for individual risk assessment in the treatment of pancreatic cancer.
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April 2020

Local and Central Evaluation of HER2 Positivity and Clinical Outcome in Advanced Gastric and Gastroesophageal Cancer-Results from the AGMT GASTRIC-5 Registry.

J Clin Med 2020 Mar 29;9(4). Epub 2020 Mar 29.

St. Vinzenz Krankenhaus Betriebs GmbH, Zams 6511, Austria.

Trastuzumab in combination with a platinum and fluorouracil is the treatment of choice for patients with advanced human epidermal growth factor receptor 2 (HER2) positive gastric cancer and gastroesophageal junction (GEJ) cancer. Pathological assessment of the HER2 status in gastric/GEJ cancer, however, still remains difficult. However, it is a crucial prerequisite for optimal treatment. The GASTRIC-5 registry was designed as an observational, multi-center research initiative comparing local and central HER2 testing. HER2 status was assessed by immunohistochemistry (IHC) and in equivocal cases (IHC score 2+) by additional in-situ hybridization. Between May 2011 and August 2018, tumor samples of 183 patients were tested in local and central pathology laboratories, respectively. Central testing revealed HER2 positivity in 38 samples (21%). Discordant HER2 results were found in 12% (22 out of 183) with locally HER2 positive/centrally HER2 negative results (9%, 17 out of 183), exceeding locally HER2 negative/centrally HER2 positive results (3%, 5 out of 183). Centrally confirmed HER2 positive patients receiving trastuzumab-based palliative first-line therapy showed a longer median overall survival compared to centrally HER2 positive patients not receiving trastuzumab (17.7 months (95% CI: 10,870-24,530) vs. 6.9 months (95% CI: 3.980-9.820), = 0.016). The findings of the GASTRIC-5 registry corroborate the challenge of HER2 testing in gastric/GEJ cancer and highlight the necessity for central quality control to optimize individual treatment options. Centrally HER2 positive patients not receiving trastuzumab had the worst outcome in a Western real-world gastric/GEJ cancer cohort.
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March 2020

High thromboembolic event rate in patients with locally advanced oesophageal cancer during neoadjuvant therapy. An exploratory analysis of the prospective, randomised intergroup phase III trial SAKK 75/08.

BMC Cancer 2020 Feb 28;20(1):166. Epub 2020 Feb 28.

Department of Medical Oncology and Haematology, Cantonal Hospital St. Gallen, Rorschacherstrasse 95, 9007, St. Gallen, Switzerland.

Background: High rates of venous thromboembolic events (VTEs), mainly in advanced disease, are reported for patients with cancer of the upper gastrointestinal tract (stomach, pancreas) and for treatment with cisplatin.

Methods: Exploratory analysis of VTEs reported as adverse events and serious adverse events in a prospective, randomised, multicentre, multimodal phase III trial according to VTEs reported as adverse events and severe adverse events. Patients with resectable oesophageal cancer (T2N1-3, T3-4aNx) were randomized to 2 cycles of chemotherapy with docetaxel 75 mg/m, cisplatin 75 mg/m followed by chemo-radiotherapy (CRT) and subsequent surgery (control arm) or the same treatment with addition of cetuximab (investigational arm).

Results: VTEs occurred in 26 of 300 patients included in the trial, resulting in an incidence rate (IR) of 8.7% [95% CI 5.7-12.4%]. A total of 29 VTEs were reported:13 (45%) VTEs were grade 2, 13 (45%) grade 3 and three (10%) fatal grade 5 events. 72% (21/29) of all VTEs occurred preoperatively (IR 6.7%): 14% (4/29) during chemotherapy and 59% (17/29) during CRT. In multivariable logistic regression only adenocarcinoma (IR 11.1%, 21/189 patients) compared to squamous cell cancer (IR 4.5%, 5/111 patients) was significantly associated with VTE-risk during treatment, OR 2.9 [95%CI 1.0-8.4], p = 0.046. Baseline Khorana risk score was 0 in 73% (19/26), 1-2 in 23% (6/26) and 3 in only 4% (1/26) of patients with VTEs.

Conclusion: A high incidence of VTEs during preoperative therapy of resectable oesophageal cancer is observed in this analysis, especially in patients with adenocarcinoma. The role of prophylactic anticoagulation during neoadjuvant therapy in resectable esophageal cancer should be further evaluated in prospective clinical trials. According to our data, which are in line with other analysis of VTE-risk in patients with oesophageal cancer patients treated with neoadjuvant cisplatin-based chemotherapy and CRT, prophylactic anticoagluation could be considered balanced against individual bleeding risks, especially in patients with adenocarcinoma. In addition to the established risk factors, oesophageal adenocarcinoma treated with neoadjuvant cisplatin-based therapy may be regarded as a high-risk situation for VTEs.

Trial Registration: Registered at, NCT01107639, on 21 April 2010.
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February 2020

Patterns of care in metastatic pancreatic cancer: patient selection in clinical routine.

Therap Adv Gastroenterol 2019 23;12:1756284819877635. Epub 2019 Sep 23.

Department of Radiation Oncology, Kantonsspital St. Gallen, Rorschacher Strasse 95, St. Gallen, 9007, Switzerland.

Background: The management of patients with metastatic pancreatic cancer (mPC) is challenging, and the optimal treatment strategy is debated among experts. In an attempt to identify treatment decision criteria and to investigate variations in the first-line management of this disease, we performed an analysis of treatment algorithms among experts in the field of pancreatic cancer. The aim of this study was to identify relevant criteria in the complex process of patient selection and decision making for the management of mPC patients.

Methods: Experts from the ABCSG (Austrian Breast and Colorectal Cancer Study Group) Pancreatic Cancer Club were contacted and agreed to participate in this analysis. Eight experts from seven centers in Austria provided their decision algorithms for the first-line treatment of patients with mPC. Their responses were converted into decision trees based on the objective consensus methodology. The decision trees were used to identify consensus and discrepancies.

Results: The final treatment algorithms included four decision criteria (performance status, age, comorbidities, and symptomatic disease) and six treatment options: mFOLFIRINOX, gemcitabine + nab-paclitaxel, gemcitabine mono, 5-FU mono, gemcitabine/erlotinib, and best supportive care (BSC).

Conclusions: We identified consensus for the treatment of young and fit patients with mFOLFIRINOX. With higher age and reduced performance status, gemcitabine + nab-paclitaxel was increasingly used. For patients with Eastern Co-operative Oncology Group Performance Status (ECOG PS) 4, BSC was the treatment of choice. Among experts, different decision criteria and treatment options are implemented in clinical routine. Despite multiple options in current recommendations, a consensus for specific recommendations was identified.
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September 2019

Treatment Algorithm for Patients With Gastric Adenocarcinoma: An Austrian Consensus on Systemic Therapy.

Anticancer Res 2019 Sep;39(9):4589-4596

Third Medical Department with Haematology, Medical Oncology, Haemostaseology, Infectious Diseases and Rheumatology, Oncology Centre, Paracelsus Medical University Salzburg, Salzburg, Austria.

Despite recent advances in the treatment of gastric cancer, mortality related to this disease is still substantial. Surgery and chemotherapy represent the cornerstones of patient management. Targeted treatments that include anti-angiogenic agents and the advent of immunotherapies can contribute to improved patient prognosis. Herein, we present an Austrian consensus on the systemic treatment of patients with gastric adenocarcinoma and lower gastroesophageal junction, including those with human epidermal growth factor receptor 2 (HER2)-positive disease. The consensus considers the curative setting, as well as first-line to late-line systemic treatment options in the palliative setting. For HER2-positive disease, first-line and second-line therapies are discussed, as well as HER2 testing. Potential future therapies are also listed, with a focus on anti-angiogenic treatments and checkpoint inhibition, that might provide a further step forward in the management of patients with gastric cancer.
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September 2019

Chemotherapy, Still an Option in the Twenty-First Century in Metastatic Colorectal Cancer?

Cardiovasc Intervent Radiol 2019 Sep 3;42(9):1213-1220. Epub 2019 Jul 3.

Department for Internal Medicine I, Medical University Vienna, Vienna, Austria.

Substantial improvements have been made in the systemic treatment of colorectal cancer over the last two decades. Median overall survival (OS) of patients with metastatic colorectal cancer (mCRC) has been constantly increased and the most recent first-line studies exceeded the 30-month median overall survival. The standard first-line regimen for mCRC is a combination of chemotherapy plus a biological agent either targeting the main angiogenic growth factor vascular endothelial growth factor (VEGF) via Bevacizumab or by antibodies targeting the epidermal growth factor receptor (EGRF) via Panitumumab or Cetuximab. Recent improvements have been shown in the efficacy of the biological agent by stratifying these agents according to the primary tumor location. In this context EGFR-inhibitors showed improved OS when used first-line in tumors derived from the left-sided colon or rectum, while tumor sidedness was not predictive for anti-VEGF-antibodies. Furthermore, the biological activity of anti-EGFR antibodies is restricted to tumors with a rat sarcoma virus (RAS)-wild-type genotype but not RAS-mutated tumors. The RAS-mutation status is not predictive for VEGF-inhibitors. Recent developments in the molecular characterisation of tumor cells led to the development of specific so called targeted therapies in colorectal cancer.
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September 2019

Efficacy and safety of regorafenib compared to placebo and to post-cross-over regorafenib in advanced non-adipocytic soft tissue sarcoma.

Eur J Cancer 2018 08 11;99:28-36. Epub 2018 Jun 11.

Department of Clinical Research and Innovation, Centre Oscar Lambret, 3 rue Combemale, 59000 Lille, France; Paris-Saclay University, Univ. Paris-Sud, CESP, INSERM, Gustave Roussy, 94805 Villejuif, France. Electronic address:

Introduction: The placebo-controlled phase-2 REGOSARC trial demonstrated the efficacy of regorafenib in patients with leiomyosarcoma, synovial sarcoma and other non-adipocytic sarcoma but not in liposarcoma. Patients initially allocated to placebo were allowed to receive regorafenib after progression. We report here an updated analysis of the trial including evaluation of regorafenib activity after cross-over.

Methods: From June 2013 to December 2014, 139 patients were enrolled in the non-adipocytic sarcoma cohorts. Median follow-up is now 32.4 months. Benefit of regorafenib versus placebo in terms of progression-free survival (PFS) and overall survival (OS) from randomisation was estimated by hazard ratio (HR) in Cox models. In the placebo arm, intra-patient benefit of regorafenib after cross-over was evaluated by the growth modulation index (GMI) (GMI was here, for each patient, PFS after cross-over regorafenib divided by PFS with placebo). Furthermore, the activity of delayed (after cross-over) versus early (at study entry) regorafenib was evaluated by comparing PFS after cross-over to regorafenib to PFS after randomisation in the regorafenib arm.

Results: PFS benefit of regorafenib as compared to placebo was confirmed with longer follow-up (HR = 0.50; 95% CI: 0.35-0.71; p < .0001). OS was not statistically significant different (HR = 0.78; 0.54-1.12; p = .18). This finding may partially be explained by the fact that 55/68 patients who progressed on placebo (81%) received cross-over Regorafenib after progression: 59% of them had a GMI ≥ 1.3 (95% CI, 45-71%). Delayed start of regorafenib was associated with a statistically non-significant shorter PFS as compared to early treatment (HR = 1.21; 0.84-1.73; p = .30) without impact on OS.

Conclusions: Observed PFS confirms that regorafenib warrants further clinical investigation in refractory non-adipocytic sarcomas.
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August 2018

A prospective, multicenter pilot study to investigate the feasibility and safety of a 1-year controlled exercise training after adjuvant chemotherapy in colorectal cancer patients.

Support Care Cancer 2018 Apr 22;26(4):1345-1352. Epub 2017 Nov 22.

Department of Internal Medicine IV, Klinikum Wels-Grieskirchen, Grieskirchnerstraße 42, A-4600, Wels, Austria.

Introduction: Despite advances in adjuvant chemotherapy, 20-30% of patients in stages II-III colorectal cancer will eventually relapse. Observational studies showed a reduction in relapse rate, colon cancer-specific mortality, and overall mortality by physical activity. Results from prospective randomized interventional studies to confirm these observational data are lacking. The aims of this prospective single-arm multicenter pilot study are to evaluate feasibility and safety of exercise training after adjuvant chemotherapy in colorectal cancer patients.

Patients And Methods: The training was performed three times per week for 1 year and was increased gradually in three phases until reaching 18 metabolic equivalent task hours per week.

Results: Overall, 30 patients were included. The planned training intensity could be achieved in all three phases. Patients experienced a performance increase of median 35.5 watt, a weight-loss of a median of 3.0 kg, and a reduction in body fat content of median 1.0% during this exercise training. The analysis showed early study termination due to non-compliance in 10/30 patients (33.3%), disease progression in 4 patients (13.3%), and serious adverse events in 2 patients (6.7%). About half of patients (46.7%) completed the pilot study as planned. Biomarker analysis from 20 patients showed a non-significant reduction in insulin-like growth factor 1 (IGF-1), insulin-like growth factor 2 (IGF-2) and insulin-like growth factor binding protein 3 (IGF-BP3) levels, significant increases in adiponectin and leptin levels, and a non-significant increase in C-peptide levels.

Conclusion: Exercise training is feasible in patients with colorectal cancer after completion of adjuvant chemotherapy. The main problem encountered during the study was compliance. To improve compliance of exercise training, several measures were adapted for the upcoming prospective randomized ABCSG C08 Exercise II study.
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April 2018

Oxaliplatin/Irinotecan/Bevacizumab Followed by Docetaxel/Bevacizumab in Inoperable Locally Advanced or Metastatic Gastric Cancer Patients - AGMT_GASTRIC-3.

Anticancer Res 2017 10;37(10):5553-5558

IIIrd Medical Department at the Paracelsus Medical University Salzburg, Salzburg Cancer Research Institute (SCRI), Cancer Cluster Salzburg (CCS), Salzburg, Austria.

Background/aim: Although high response rates using the doublet-chemotherapy of oxaliplatin and irinotecan as well as its combination with cetuximab in advanced gastric cancer were shown in previous trials, time to progression was short, suggesting acquired chemotherapy resistance.

Patients And Methods: Sequential chemotherapy (oxaliplatin and irinotecan followed by docetaxel) combined with bevacizumab was investigated in the GASTRIC-3 trial. Patients achieving at least stable disease were continued on maintenance bevacizumab.

Results: Objective response rate was available in 33 patients: Complete response (CR) 12.1%, partial response (PR) 39.4%, stable disease (SD) 27.3%. Median time to progression was 7.0 months (95%CI=5.0-11.0) and median overall survival was 11 months (95%CI=9.0-15.0). Of note, two patients continue to receive bevacizumab maintenance therapy for more than 5 years with ongoing CR.

Conclusion: Combining sequential chemotherapy with oxaliplatin/irinotecan and docetaxel with bevacizumab followed by bevacizumab maintenance is feasible and clinically active in advanced gastric cancer.
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October 2017

Neoadjuvant Chemotherapy with Capecitabine, Oxaliplatin and Bevacizumab Followed by Concomitant Chemoradiation and Surgical Resection in Locally Advanced Rectal Cancer with High Risk of Recurrence - A Phase II Study.

Anticancer Res 2017 05;37(5):2683-2691

Department of Internal Medicine IV, Wels-Grieskirchen Medical Hospital, Wels, Austria.

Aim: To evaluate feasibility and safety of neoadjuvant chemotherapy with capecitabine, oxaliplatin and bevacizumab followed by concomitant standard chemoradiation and surgical resection in patients with high-risk locally advanced rectal cancer.

Patients And Methods: Magnetic resonance imaging (MRI)-defined high-risk cT3/4 rectal cancer patients were treated with 3 cycles of neoadjuvant chemotherapy with capecitabine (1,000 mg/m twice daily days 1-14, 22-35, 43-56), oxaliplatin (130 mg/sqm on days 1, 22, 43) and bevacizumab (7.5 mg/kg on days 1, 22, 43) followed by capecitabine (825 mg/m twice daily on radiotherapy days week 1-4) concomitantly with radiotherapy (1.8 Gy daily up to 45 Gy in 5 weeks) and surgical resection by total mesorectal excision. Feasibility, safety, response rate and postoperative morbidity were evaluated.

Results: Twenty-five patients were recruited. Median age was 62 years (range=24-78 years) and all patients had Eastern Cooperation Oncology Group (ECOG) performance status 0. From all patients, 79.2% finished neoadjuvant chemotherapy. Twenty patients underwent surgery. Pathologic complete remission rate, R0 resection and T-downstaging were achieved in 25%, 95% and 54.2% of the "intention to treat" (ITT) patients. The most common grade 3 adverse events (AEs) during neoadjuvant chemotherapy were diarrhea (16.6%) and mucositis (12.5%). In one patient, a grade 4 acute renal failure occurred (4.2%). During chemoradiation, skin reactions (5.3%) were the most common grade 3 AEs. Two major perioperative complications required re-intervention.

Conclusion: Neoadjuvant chemotherapy with bevacizumab, capecitabine and oxaliplatin followed by concomitant standard chemoradiation is feasible in patients with high-risk locally advanced rectal cancer (LARC) and resulted in complete pathologic remission (pCR) rate of 25% and neoadjuvant chemotherapy completion rate of 80%.
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May 2017

Treatment of patients with refractory metastatic cancer according to molecular profiling on tumor tissue in the clinical routine: an interim-analysis of the ONCO-T-PROFILE project.

Genes Cancer 2016 Sep;7(9-10):301-308

Department of Haematoloy and Oncology, Innsbruck Medical University, Austria.

Introduction: Patients with refractory metastatic cancer have been shown to benefit from molecular profiling of tumor tissue. The ONCO-T-PROFILE project was launched in March 2014 at the Innsbruck Medical University. Within 2 years our project aims to recruit 110 patients with stage IV cancer refractory to standard therapy. Our data presented here are based on an interim-analysis.

Methods: Tumor tissue specimens were submitted for molecular profiling to the certified laboratory (Caris Life Science, USA). Druggable tumor targets were selected based on biomarker status to agents with potential clinical benefit. Clinical benefit was defined as a PFS ratio (=PFS upon treatment according to the molecular profile/ PFS upon the last prior therapy) ≥ 1.3.

Results: As of April 2015, tumors from 50 patients have been molecularly profiled and one or more targets were detectable in 48 specimens (98%). So far, 19 (38%) patients have been treated according to their molecular tumor profile. To date, 8 (42%) patients have reached a PFS ratio of ≥ 1.3.

Conclusions: We could show that molecular profiling is feasible in the clinical routine. A proportion of patients might benefit from an individualized treatment approach based on molecular profiling. As a result, we will proceed to enroll patients in ONCO-T-PROFILE.
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September 2016

Safety and efficacy of regorafenib in patients with advanced soft tissue sarcoma (REGOSARC): a randomised, double-blind, placebo-controlled, phase 2 trial.

Lancet Oncol 2016 Dec 14;17(12):1732-1742. Epub 2016 Oct 14.

Methodology and Clinical Research Platform of SIRIC OncoLille, Lille, France. Electronic address:

Background: Regorafenib is a multikinase inhibitor with proven activity in refractory gastrointestinal stromal tumours and chemotherapy-refractory advanced colorectal cancers. We assessed this agent's efficacy and safety in patients with metastatic soft tissue sarcomas previously treated with anthracycline.

Methods: In this randomised, double-blind, phase 2 trial undertaken in France and Austria, we enrolled patients aged 18 years and older with advanced soft tissue sarcomas who had received previous doxorubicin or other anthracycline treatment. These patients were randomly assigned (1:1) into one of the following four cohorts: liposarcoma, leiomyosarcoma, synovial sarcoma, and other sarcomas. Participants were treated with oral regorafenib (160 mg per day 3 weeks on and 1 week off) or matched placebo. Patients receiving placebo were offered optional crossover in case of centrally confirmed disease progression. The random allocation schedule was computer-generated with permuted blocks of four patients, with two stratification factors: country (France or Austria) and previous exposure to pazopanib (yes or no). Eligibility criteria included patients with histologically proven advanced and inoperable soft tissue sarcomas with intolerance or failure to doxorubicin or other anthracycline-based chemotherapy and at least one unidimensionally or bidimensionally measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1). The primary endpoint was RECIST-based progression-free survival after central radiological review in the intention-to-treat population. Patients, physicians, and radiologists of the panel were masked to treatment allocation. This study is still open for recruitment for an additional stratum (patients previously treated with pazopanib) and registered with, NCT01900743.

Findings: From Aug 5, 2013, to Nov 26, 2014, 182 patients were randomly assigned to one of four cohorts and included in the final analysis. At the cutoff date (Jan 7, 2016), the number of required events was reached for the four cohorts. In the liposarcoma cohort, progression-free survival was 1·1 months (95% CI 0·9-2·3) with regorafenib versus 1·7 months (0·9-1·8) with placebo (HR 0·89 [95% CI 0·48-1·64] p=0·70). In the leiomyosarcoma cohort, progression-free survival was 3·7 months (95% CI 2·5-5·0) with regorafenib versus 1·8 (1·0-2·8) months with placebo (HR 0·46 [95% CI 0·46-0·80] p=0·0045). In the synovial sarcoma cohort, progression-free survival was 5·6 months (95% CI 1·4-11·6) with regorafenib versus 1·0 (0·8-1·4) with placebo (HR 0·10 [95% CI 0·03-0·35] p<0·0001). In the other sarcoma cohort, progression-free survival was 2·9 months (95% CI 1·0-7·8) with regorafenib versus 1·0 (0·9-1·9) with placebo (HR 0·46 [95% CI 0·25-0·81] p=0·0061). Before crossover, the most common clinically significant grade 3 or higher adverse events were arterial hypertension (17 [19%] events in the 89 patients in the regorafenib group vs two [2%] events in the 92 patients in the placebo group), hand and foot skin reaction (14 [15%] vs no events) and asthenia (12 [13%] vs six [6%]). One treatment-related death occurred in the regorafenib group due to liver failure.

Interpretation: Regorafenib has an important clinical antitumour effect in non-adipocytic soft tissue sarcomas, improving progression-free survival. Regorafenib should be further evaluated in this setting, and its therapeutic role has to be defined in the context of the growing therapeutic armamentarium, already including one approved multikinase inhibitor, pazopanib.

Funding: Bayer HealthCare.
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December 2016

Long-term surveillance of locally advanced rectal cancer patients with neoadjuvant chemoradiation and aggressive surgical treatment of recurrent disease: a consecutive single-centre experience.

Int J Colorectal Dis 2015 Dec 21;30(12):1705-14. Epub 2015 Aug 21.

Department of Visceral, Transplant and Thoracic Surgery, Center of Operative Medicine, Innsbruck Medical University, Anichstrasse 35, A-6020, Innsbruck, Austria.

Purpose: The aim of this study was to analyse the long-term outcome of rectal cancer patients who submitted to preoperative chemoradiation with consecutive intensive follow-up and aggressive surgical treatment of recurrent disease.

Methods: Patients with locally advanced (cT3-4 Nx M0-1) mid/low rectal cancer were treated at a tertiary university hospital with preoperative long-course chemoradiation followed by resection (according to a prospective study protocol). After resection, all patients were urged to participate in a standardised, risk-independent intensive follow-up program. All curatively treated patients (n = 153, 96 %) were included in our long-term analysis with respect to curative re-resection of recurrent disease.

Results: Of 153 patients, 143 (93 %) participated in our follow-up program: 63 % were surveyed longer than 5 years after primary therapy (mean follow-up 75 months, 95 % CI 67.8-82.2). Fifty-five (36 %) patients developed cancer recurrence (mean 27.8 months, 95 % CI 20.6-34.9, range 3-108), giving a disease-free survival rate of 68.5 and 60.7 % at 5 and 10 years; 21 (38 %) patients were re-resected curatively and 58 (38 %) patients died during the observation period, giving an overall survival rate of 70.8 and 57.5 % at 5 and 10 years. Multivariate analysis found tumour differentiation (P < 0.01), operative procedure (P < 0.05) and downstaging (P < 0.01) to be independent variables influencing overall survival.

Conclusions: The combination of multimodal therapy and aggressive surgical treatment of metastases including repeated re-resections in curative intention is relevant in order to chronify the disease. Thus, both intensive and extended follow-up beyond 5 years appear to be mandatory.
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December 2015

Oesophageal cancer: exploring controversies overview of experts' opinions of Austria, Germany, France, Netherlands and Switzerland.

Radiat Oncol 2015 May 21;10:116. Epub 2015 May 21.

Department of Haematology and Oncology, Swiss Group for Clinical Cancer Research (SAKK), Kantonsspital St. Gallen, St. Gallen, Switzerland.

Background: Oesophageal carcinoma is a rare disease with often dismal prognosis. Despite multiple trials addressing specific issues, currently, many questions in management remain unanswered. This work aimed to specifically address areas in the management of oesophageal cancer where high level evidence is not available, performing trials is very demanding and for many questions high-level evidence will not be available in the forseeable future.

Methods: Two experts of each national, oesophageal cancer research group from Austria, France, Germany, the Netherlands and Switzerland were asked to provide statements to controversial issues. After an initial survey, further questions were formulated and answered by all experts. The answers were then discussed and qualitatively analysed for consensus and controversy.

Results: Topics such as indications for PET-CT, reasons for induction chemotherapy, radiotherapy dose, the choice of definitive chemo-radiotherapy versus surgery in squamous cell cancer, the role of radiotherapy in adenocarcinoma and selected surgical issues were identified as topics of interest and discussed.

Conclusion: Areas of significant controversy exist in the management of oesophageal cancer, mostly due to high-level evidence. This is not expected to change in the upcoming years.
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May 2015

Preoperative treatment with capecitabine, cetuximab and radiotherapy for primary locally advanced rectal cancer--a phase II clinical trial.

Anticancer Res 2014 Nov;34(11):6767-73

Department of Internal Medicine IV, Hospital Wels-Grieskirchen, Wels, Austria.

Background/aim: To investigate the feasibility and safety of preoperative capecitabine, cetuximab and radiation in patients with MRI-defined locally advanced rectal cancer (LARC, cT3/T4).

Patients And Methods: 31 patients with LARC were treated with cetuximab and capecitabine concomitantly with 45 Gy radiotherapy and resected by total mesorectal excision. Histopathological response and association with KRAS status was evaluated.

Results: R0-resection was possible in 27 of 31 (86%) patients. No complete pathological remission was observed. Radiochemotherapy with capecitabine and cetuximab was safe to administer and diarrhea was the main toxicity. KRAS-status did not correlate to down-staging or pathological response concerning T- or N-stage.

Conclusion: Neoadjuvant therapy with capecitabine and cetuximab in combination with radiotherapy did not lead to complete pathological remission. Treatment tolerability was excellent and toxicity remained low. KRAS status did not influence treatment outcomes. Capecitabine in combination with radiotherapy remains a standard therapy for locally advanced rectal cancer.
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November 2014

Gastrointestinal stromal tumors: diagnosis, therapy and follow-up care in Austria.

Wien Med Wochenschr 2013 Mar 19;163(5-6):137-52. Epub 2013 Mar 19.

Department of Surgery, General Hospital, Wiener Neustadt, Vienna, Austria.

Optimal treatment for patients suffering from gastrointestinal stromal tumors (GIST) is based on an interdisciplinary treatment approach. Austrian representatives of Medical and Surgical Oncology, Pathology, Radiology, Nuclear Medicine, Gastroenterology, and Laboratory Medicine issued this manuscript on a consensual base within the context of currently available and published literature. This paper contains guidelines and recommendations for diagnosis, therapy, and follow-up of GIST patients in Austria.
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March 2013

Pegfilgrastim prophylaxis in patients at different levels of risk for chemotherapy-associated febrile neutropenia: an observational study.

Curr Med Res Opin 2013 May 19;29(5):505-15. Epub 2013 Mar 19.

University Hospital, Medical University of Innsbruck, Innsbruck, Austria.

Background: Guidelines for using granulocyte colony-stimulating factor (G-CSF) in patients receiving chemotherapies with 10-20% (intermediate) risk for febrile neutropenia (FN) recommend additional assessment of patient-related FN risk factors.

Objective: The current study evaluated adherence to guideline recommendations and analysed modalities of pegfilgrastim use.

Methods: Adult cancer patients scheduled to receive a chemotherapy regimen assessed by the investigators as intermediate FN risk and who received pegfilgrastim were prospectively enrolled in this observational study from 2007-2010. Risk factors at study entry, treatment modalities and FN assessment were documented by investigators, whereas guideline adherence was centrally checked in a post-hoc analysis, according to guideline categorizations.

Results: Thirty-seven centres enrolled 335 evaluable patients with solid and hematologic neoplasias. Although physicians initially rated the FN risk of all chemotherapies as intermediate, after central re-assessment this applied only to 63.9% of regimens; 21.2% were reassessed as low risk and 14.9% as high risk. Pegfilgrastim was used as primary prophylaxis in 80.3% of all patients. The most frequent FN risk factors considered by physicians when deciding to use pegfilgrastim were female gender, advanced disease, age ≥ 65 years, and anaemia. FN incidence was higher in patients with ≥ 4 FN risk factors than those with <4 risk factors (10% vs. 4.3%; p = 0.055) and in patients with severe comorbidity than those without (13.6% vs. 4.5%; p = 0.014). Overall FN rate was 5.7%.

Limitations: Due to the observational design of the study, findings are descriptive in nature. Post-hoc assessment of chemotherapy FN risk was determined by author's opinion in some cases.

Conclusions: Overall, there was good adherence of Austrian physicians to guideline recommendations; however, there are chemotherapy regimens and clinical settings in which FN risk assignment is unclear in the literature. FN incidence with pegfilgrastim prophylaxis was similar to that reported in other observational and randomized studies.
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May 2013

Hemoglobin level at initiation of darbepoetin alfa: impact on need for transfusion and associated costs in chemotherapy-induced anemia treatment in Europe.

Support Care Cancer 2013 Feb 24;21(2):485-93. Epub 2012 Jul 24.

Welsh School of Pharmacy, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff, CF10 3NB, UK.

Purpose: Erythropoiesis-stimulating agents can reduce red blood cell transfusion rates in patients developing anemia while receiving chemotherapy. We investigated potential cost savings from reduced transfusion rates in patients starting darbepoetin alfa (DA) at higher versus lower hemoglobin (Hb) levels.

Methods: Two systematic literature reviews were performed: transfusion outcomes in patients receiving DA stratified by baseline Hb level and costs of transfusion in Europe. Potential cost savings were calculated by multiplying the difference in transfusion rates between Hb levels by the midpoint of transfusion costs.

Results: Despite differences in baseline characteristics, treatment duration and analysis technique, the clinical studies (n = 8) showed that fewer transfusions were required when DA was initiated at higher versus lower Hb levels. The economic studies (n = 9) showed that 1 unit of transfusion ranged from 130 to 537 (2010-adjusted values). Cost savings from initiating DA at higher versus lower Hb levels were 503-2,226 (2 units transfused) and 880-3,895 (3.5 units) per ten patients.

Conclusions: Transfusion incidence increases with DA initiation at lower Hb levels. Potential cost savings depend on the number of units transfused and cost items included. DA initiation according to guidelines can reduce transfusions and potentially reduce transfusion-associated costs.
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February 2013

First experience with proteasome inhibitor treatment of radioiodine nonavid thyroid cancer using bortezomib.

Clin Nucl Med 2012 Jun;37(6):539-44

Department of Nuclear Medicine, Innsbruck Medical University, Austria.

Purpose: Radioiodine nonavid thyroid cancer (TC) is a rare disease entity with a poor prognosis. Despite a multimodal therapeutic approach including surgery, chemotherapy, and external beam radiation, radioiodine nonavid TC accounts for a high number of TC-associated deaths. The aim of this investigation was to evaluate the response rate of progressive TC patients to treatment with the proteasome inhibitor bortezomib.

Materials And Methods: Seven patients with inoperable, metastasized progressive TC proven to be radioiodine nonavid were included into this pilot study. Patients received bortezomib intravenously with a standardized dose of 1.3 mg/m on days 1, 4, 8, and 11. All patients underwent 3 therapeutic cycles with an interval of 10 days. [F]2-deoxy-2-fluoro-D-glucose positron emission tomography (F-FDG PET) and measurements of thyroglobulin levels were performed before, during, and after therapy, with a 6-week interval to post-therapeutic follow-up.

Results: Stable disease was seen after proteasome inhibitor therapy in 4 of the 7 patients. Two of the 7 patients showed decrease of maximum standardized uptake value in both post-therapeutic follow-up investigations, and one of these cases also had decreasing thyroglobulin levels. Two patients experienced stable disease during the posttherapeutic follow-up. Two patients showing a mixed response had an improvement in their clinical situation. One patient had rapidly progressive disease, and died 3 months after the last therapeutic cycle. Adverse events included mild polyneuropathy in 2 patients and alterations of the blood count up to WHO (World Health Organization) grade 2 in 5 patients.

Conclusion: Proteasome inhibitor treatment with bortezomib is a promising therapeutic approach in TC patients without an established treatment alternative. The development of a specific therapeutic regimen for the treatment of radioiodine nonavid TC is warranted.
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June 2012

Oxaliplatin, irinotecan and cetuximab in advanced gastric cancer. A multicenter phase II trial (Gastric-2) of the Arbeitsgemeinschaft Medikamentose Tumortherapie (AGMT).

Anticancer Res 2011 Dec;31(12):4439-43

St.Vinzenz Krankenhaus Betriebs GmbH, Sanatoriumstr. 43, A-6511 Zams, Austria.

Background: Patients suffering from advanced gastric cancer still have a poor prognosis and treatment options are limited. In our previous phase II trial (AGMT-Gastric-1), we showed that the combination of oxaliplatin and irinotecan was well tolerated and effective. The same chemotherapy regimen was now tested in combination with cetuximab in a multicenter phase II trial.

Patients And Methods: Oxaliplatin at 85 mg/m(2) biweekly and irinotecan at 125 mg/m(2) biweekly were combined with cetuximab at 400 mg/m(2) loading dose and subsequent weekly infusions of 250 mg/m(2). Fifty-one patients with histologically proven unresectable and/or metastatic gastric adenocarcinoma were treated in the first line setting. The median age was 62 years. A single metastatic site was found in 24 patients, 27 patients had multiple metastatic sites.

Results: Frequently reported adverse events (in more than 20% of patients) were predominantly grade 1 or 2 and included neutropenia (35%), thrombocytopenia (33%), anemia (73%), nausea (45%), diarrhea (57%), alopecia (22%), and fatigue (37%). Grade 3/4 toxicities included neutropenia in 9/1 patients., thrombocytopenia in 1/0 patients, anemia in 3/1 patients, nausea in 2/0 patients, and diarrhea in 7/2 patients. Sensory neuropathy occurred mostly as grade 1 and 2 in 37% of patients, grade 3 neurotoxicity was observed in 7 patients. Acne-like rash grades 1/2/3/4 were reported in 31%/20%/6%/2% of patients respectively. Thirteen patients discontinued the study due to neutropenia (n=5), nausea/vomiting (n=1), diarrhea (n=1), toxic colon (n=2), and allergic reaction to cetuximab at first (n=2), second (n=1) or third infusion (n=1). Thirty-five patients were assessable for response, with 1 patient (3%) showing a complete response, 21 patients (60%) a partial response, 7 patients (20%) a stable disease, and 6 patients (17%) a progressive disease respectively. The median time to progression was 24.8 weeks, median overall survival was 38.1 weeks. All patients tested had a wild type KRAS status.

Conclusion: The combination of oxaliplatin and irinotecan with cetuximab is safe and its action established in advanced gastric cancer.
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December 2011

Triple induction chemotherapy and chemoradiotherapy for locally advanced esophageal cancer. A phase II study.

Anticancer Res 2011 Dec;31(12):4407-12

Innsbruck Medical University, Department of Internal Medicine I, Anichstrasse 35, 6020 Innsbruck, Austria.

Background: This phase II trial assessed the feasibility and safety of induction chemotherapy with cisplatin (25 mg/m(2) d1-5, d29-34)/docetaxel (75 mg/m(2) d1, d29)/5-fluorouracil (5-FU, 750 mg/m(2) d1-5, d 29-34) followed by external beam radiotherapy concurrent with docetaxel (15 mg/m(2) d1,8,15,22) and 5-FU (300 mg/m(2) continuous infusion on the days of radiotherapy).

Patients And Methods: Twenty-four patients with locally advanced carcinoma of the esophagus were included. Following chemotherapy and chemoradiation eligible patients underwent esophagectomy. If surgery could not be performed patients received definitive radiation.

Results: Sixteen patients underwent resection. Pathologic complete remission was achieved in 5 of those 16 patients, 13 patients had downstaging of disease. R0 resection was feasible in all 16 patients. Main grade 3 and 4 toxicities were neutropenia in 10 patients, diarrhea in 4 and postoperative morbidity in 9 patients. At a median follow-up of 16.5 months 15 patients are alive; median survival has not yet been reached.

Conclusion: Neoadjuvant treatment with cisplatin/docetaxel/5-fluorouracil followed by chemoradiation with docetaxel/5-fluorouracil is safe, feasible, and effective.
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December 2011

[Consensus diagnosis and therapy of soft tissue sarcoma].

Wien Klin Wochenschr 2012 Feb 28;124(3-4):85-99. Epub 2011 Oct 28.

Klinische Abteilung für Onkologie, Universitätsklinik für Innere Medizin, Wien, Austria.

Soft tissue sarcomas are heterogeneous tumours and relatively uncommon. There have been advances over the past years concerning pathology, clinical behaviour, diagnosis strategies and the treatment. To summarize these advances as well as making it public is one of the goals of the following consensus guidelines. But why do we need special guidelines for Austria? There are international guidelines published by the European Society of Medical Oncology (ESMO) and the National Comprehensive Cancer Network (NCCN). The cause is that we need an explanation of the matrix the ESMO and the NCCN gave according to our clinical practice, the local requirements and facilities in Austria. The following recommendations were drawn up following a consensus meeting of sarcoma specialists from the three high volume centres located at the medical universities in Austria. All fields of involved physicians from diagnosis to therapy worked together to know that soft tissue sarcomas are an interdisciplinary challenge and multimodal treatment is essential. For this reason, these guidelines not only explain but also give the state of the art and clear recommendations. One of the most important guidelines is that any patient with a suspected soft tissue sarcoma should be referred to one of the three university centres and managed by a specialist sarcoma multidisciplinary team. We hope that the consensus is helpful for the clinical practice and improves the quality of care for patients with soft tissue sarcomas in Austria.
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February 2012

[99mTc]demotensin VI: biodistribution and initial clinical results in tumor patients of a pilot/phase I study.

Cancer Biother Radiopharm 2011 Oct 1;26(5):557-63. Epub 2011 Sep 1.

Department of Nuclear Medicine and Endocrinology, General Hospital of Linz, Linz, Austria.

Purpose: Neurotensin subtype 1 receptor overexpression is found in a variety of human tumors. The aim of this pilot/phase I study was to assess the safety profile, pharmacokinetics, and imaging characteristics of (99m)Tc-Demotensin VI in tumor patients.

Methods: Scintigraphy with (99m)Tc-Demotensin VI was performed in 14 patients (2 female and 12 male) with advanced tumor stages. The diagnoses were pancreatic adenocarcinoma (n=4), small cell lung cancer (SCLC) (n=4), non-small cell lung cancer (NSCLC) (n=4), and colon carcinoma (n=2). Patients were injected with 500-550 MBq (99m)Tc-Demotensin VI. Blood samples were taken at various time points and urine was also collected up to 24 hours post-injection (p.i.) Planar images were acquired at 15-30 minutes, 1-2 hours, 4 hours, and 24 hours p.i. with additional SPECT imaging at 4 hours.

Results: Radiochemical purity always exceeded 95% up to 4 hours. Urinary and blood excretion was rapid with 5.05% ID (mean: n=5) in plasma after 4 hours. No side effects were observed after injection of (99m)Tc-Demotensin VI. Focal tracer accumulation was observed in 3 patients with brain metastases due to NSCLC, although specificity of this uptake could not be proven. Further, no tumor-related findings were observed. Although stability tests in human plasma revealed that (99m)Tc-Demotensin VI remained intact up to 2 hours incubation, ex vivo urine analysis indicated rapid metabolism.

Conclusion: (99m)Tc-Demotensin VI was well tolerated by patients and showed favorable pharmacokinetics; however, tumor targeting was limited to brain metastases. Further studies on stability issues and receptor characterization in tumors are warranted to introduce neurotensin receptors (NTSR) imaging into the clinic.
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October 2011

Preoperative treatment with capecitabine, bevacizumab and radiotherapy for primary locally advanced rectal cancer--a two stage phase II clinical trial.

Radiother Oncol 2012 Jan 7;102(1):10-3. Epub 2011 Jul 7.

Department of Internal Medicine IV, Klinikum Wels-Grieskirchen, Austria.

Background And Purpose: The aim of this single-arm multicenter phase II clinical trial was to assess the feasibility and tolerability of preoperative radiotherapy and simultaneous capecitabine and bevacizumab. Secondary endpoints were downstaging-rate and induction of complete pathological response.

Material And Methods: Patients with cT3 rectal cancer were eligible. Capecitabine (825 mg/sqm twice daily on radiotherapy-days weeks 1-4) and bevacizumab (5 mg/kg on days 1, 15 and 29) were administered concurrently to pelvic radiotherapy (1.8 Gy daily up to 45 Gy in 5 weeks). Surgery followed 6-8 weeks later. A two-stage trial was designed with early termination at eight patients if more than three patients had experienced a common toxicity criteria ≥grade 3 according to the NCI CTC guidelines.

Results: In the first stage eight patients were enrolled. Median age was 70 years (range 55-76) and ECOG PS 0/1 (%) was 87.5/12.5. Major side effects were mostly intestinal bleeding (grade 3, 25%), diarrhea (grade 3, 25%), perianal and abdominal pain (grades 3 and 4, 25%) followed by anemia (grade 3, 12.5%). Tumor downstaging was observed in 37.5% of patients with complete pathological response in two patients (25%).

Conclusions: After interim analysis of feasibility and tolerability, accrual was terminated according to protocol due to ≥grade 3 toxicities in 50% of patients. Complete pathological response was seen in 25% of patients but was accompanied by considerable toxicity. Further clinical trials are needed to clarify the role of bevacizumab in this setting.
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January 2012

Preoperative oxaliplatin, capecitabine, and external beam radiotherapy in patients with newly diagnosed, primary operable, cT₃NxM0, low rectal cancer: a phase II study.

Strahlenther Onkol 2011 Feb 21;187(2):100-7. Epub 2011 Jan 21.

Department of Surgery, Paracelsus Private Medical University, Salzburg, Austria.

Purpose: In patients with locally advanced rectal cancer (LARC), preoperative chemoradiation is known to improve local control, and down-staging of the tumor serves as a surrogate for survival. Intensification of the systemic therapy may lead to higher downstaging rates and, thus, enhance survival. This phase II study investigated the efficacy and safety of preoperative capecitabine and oxaliplatin in combination with radiotherapy.

Patients And Methods: Patients with LARC of the mid and lower rectum, T₃NxM0 staged by MRI received radiotherapy (total dose 45 Gy) in combination with oral capecitabine (825 mg/m² twice a day on radiotherapy days; weeks 1-4) and oxaliplatin 50 mg/m² intravenously (days 1, 8, 15, and 22). Efficacy was evaluated as rate of tumor down-categorization at the T level.

Results: A total of 59 patients were enrolled (19 women, 40 men; median age of 61 years) and all were evaluable for efficacy and toxicity. Down-categorization at the T level was observed in 53% with pathological complete response in 6 patients (10%). Actual total radiotherapy, oxaliplatin and capecitabine doses received were 97%, 90%, and 93% of the protocol-specified preplanned doses, respectively. Grade 3/4 toxicity was observed in 15 patients (25%). The most frequent was diarrhea (12%).

Conclusions: Preoperative chemoradiation with capecitabine and oxaliplatin is feasible in patients with MRI-proven cT₃ LARC. The only clinically relevant toxicity was diarrhea. Overall, efficacy of the multimodality treatment was good, but not markedly exceeding that of 5-FU- or capecitabine-based chemoradiation approaches.
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February 2011

First annual report of the Austrian CML registry.

Wien Klin Wochenschr 2010 Oct 11;122(19-20):558-66. Epub 2010 Oct 11.

Department of Internal Medicine V, Haematology & Oncology, Innsbruck Medical University, Innsbruck, Austria.

The Austrian chronic myeloid leukemia (CML) registry monitors individual disease courses, treatments applied, clinical outcome, and side effects of CML patients on a nationwide basis to provide data on the "real-life" situation and to complement the information and interpretation gained from the selected patient population observed in clinical trials. This report summarizes the Austrian CML registry data as of March 2009. A total of 179 patients have been registered with a median number of 1012 follow-up visits and median observation duration of 20 months. At diagnosis most patients (n = 163) were in chronic phase (early, late, and secondary), whereas only 4 were in advanced phase. A total of 137 patients were treated with tyrosine kinase inhibitors (TKIs), of which 14 received first and second generation TKIs sequentially. Other treatment modalities included chemotherapy or interferon and stem cell transplantation (SCT). Cumulative incidence rates for complete hematological responses (CHR) were 91.6% and 94.4% at 12 and 24 months, respectively, compared to cumulative incidence rates of complete cytogenetical response rates of 64% and 80% at these timepoints. A total of 5 patients progressed from chronic phase to accelerated (n = 3) and blastic phase (n = 2) while receiving imatinib standard dose. Estimated overall survival (OS) rate at 60 months was 90% and progression free survival (PFS) according to European Leukemia Net (ELN) failure definition was 58%.
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October 2010