Helmut Oettle

Publications (51)131.89 Total impact

• Article: K-ras mutations in the plasma correspond to computed tomographic findings in patients with pancreatic cancer.

  Jan Däbritz, Roman Preston, Joachim Hänfler, Helmut Oettle
  Pancreas 10/2011; 41(2):323-5. · 2.39 Impact Factor
• Article: Transforming growth factor beta in pancreatic cancer.

  Andreas Hilbig, Helmut Oettle
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  ABSTRACT: Pancreatic cancer has high incidence and mortality rates, and effective treatment remains a clinical challenge. As deregulation of the cytokine transforming growth factor beta (TGF-β) contributes to the progression of pancreatic carcinoma, the TGF-β pathway has been targeted using various strategies, including small molecule inhibitors of TGF-βRI, TGF-β-specific neutralizing antibodies and antisense compounds. As increased TGF-β2 levels in serum or tumor tissue of patients with pancreatic cancer correlated with poor prognosis, inhibition of TGF-β2 synthesis via the antisense oligonucleotide trabedersen (AP 12009) is a promising approach.
  Current pharmaceutical biotechnology 05/2011; 12(12):2158-64. · 3.40 Impact Factor
• Article: Best supportive care (BSC) versus oxaliplatin, folinic acid and 5-fluorouracil (OFF) plus BSC in patients for second-line advanced pancreatic cancer: a phase III-study from the German CONKO-study group.

  Uwe Pelzer, Ingo Schwaner, Jens Stieler, Mathias Adler, Jörg Seraphin, Bernd Dörken, Hanno Riess, Helmut Oettle
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  ABSTRACT: Gemcitabine usually given until progressive disease (PD) is the main first-line treatment option for patients with inoperable advanced pancreatic cancer (APC). Currently there is no accepted active regimen for second-line chemotherapy. Previous phase II studies suggest clinical relevant activity of oxaliplatin, folinic acid and 5-FU (OFF). We initiated a phase III multicentre study comparing OFF versus best supportive care (BSC) in patients with APC progressing while on gemcitabine therapy. In this open randomized study, patients with CT and/or MRI confirmed progressive disease while on gemcitabine therapy were randomized 1:1 to OFF or BSC. Stratification included duration of first-line therapy (<3, 3 to 6 and >6 months), performance status (KPS 70-80%; 90-100%) and tumour stage (M1/M0). OFF consisted of folinic acid 200mg/m(2) followed by 5-fluorouracil 2g/m(2) (24h) on d1, d8, d15, d22 and oxaliplatin 85 mg/m(2) on days 8 and 22. After a rest of 3 weeks the next cycle was started on d43. A total of 165 patients were calculated to demonstrate a doubling of survival time after progression on first-line therapy. After inclusion of forty six patients the trial was terminated according to predefined protocol regulations due to insufficient accrual (lack of acceptance of BSC by patients and physicians. Patient characteristics were well balanced between both study arms. The OFF regimen was well tolerated with more patients with grade I/II paraesthesia and grade II/III nausea/emesis and diarrhoea. Median second-line survival was 4.82 [95% Confidence Interval; 4.29-5.35] months for OFF treatment and 2.30 [95% CI; 1.76-2.83] months with BSC alone (0.45 [95% CI: 0.24-0.83], p = 0.008). Median overall survival for the sequence GEM-OFF was 9.09 [95% CI: 6.97-11.21] and 7.90 [95% CI: 4.95-10.84] months for GEM-BSC (0.50 [95% CI: 0.27-0.95], p = 0.031) respectively. Although stopped prematurely, this randomized trial provides at first time evidence for the benefit of second-line chemotherapy as compared to BSC alone for patients with APC. OFF significantly prolonged survival time compared to BSC alone after failure of first-line therapy with gemcitabine.
  European journal of cancer (Oxford, England: 1990) 05/2011; 47(11):1676-81. · 4.12 Impact Factor
• Article: First-line treatment of pancreatic cancer patients with the combination of 5-fluorouracil/folinic acid plus gemcitabine: a multicenter phase II trial by the CONKO-study group.

  Uwe Pelzer, Dirk Arnold, Peter Reitzig, Julia Herrenberger, Friedrich Wilhelm Korsten, Manfred Kindler, Jens Stieler, Bernd Dörken, Hanno Riess, Helmut Oettle
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  ABSTRACT: This open-label, multi-center phase II study investigated the efficacy and safety of the combination of 5-fluorouracil (5-FU)/folinic acid (FA) plus gemcitabine (GFF) in patients with advanced pancreatic cancer. The study is based on our completed dose finding phase I trial. A total of 90 patients (pts) were recruited between 02/2000 and 04/2002 to receive 5-FU 750 mg/m(2) (24 h, i.v.), FA 500 mg/m(2) (2 h, i.v.) and gemcitabine 1,000 mg/m(2) (30 min, i.v.) on days 1, 8, 15, and 22. Treatment was repeated on day 43 until disease progression. The primary objective was the 1-year survival rate. The trial was conducted in compliance with the Declaration of Helsinki. The 1-year survival rate was 25% [95% CI: 16-34], median overall survival was 6.8 months [95% CI: 5.13-8.45], 9 patients showed partial responses (PR) so that the overall response rate was 10.3%. Overall control rate (PR + stable disease for at least 6 months) was 56%. Median time to progression was 4.6 months [95% CI: 3.68-5.52]. In 402 GFF cycles, we observed adverse events grade 3 in up to 10% of patients and grade 4 below 5% of patients. The GFF combination appears to be effective and well tolerated. This intravenous regimen represents an intensified therapy with low frequency of toxicities and seems to be convenient for patients who are unable to get oral anti-neoplastic medication. After these encouraging results, the German CONKO-002 trial investigated the GFF regimen versus single-agent gemcitabine.
  Cancer Chemotherapy and Pharmacology 03/2011; 68(5):1173-8. · 2.83 Impact Factor
• Article: [Gastrointestinal tumors--interdisciplinary discussion over new data].

  Dirk Arnold, Rainer Fietkau, Susanna Hegewisch-Becker, Thomas Höhler, Wolfram Trudo Knoefel, Stefan Kubicka, Hauke Lang, Torsten Liersch, Markus Luster, Helmut Oettle, Anke Reinacher-Schick, Karsten Ridwelski, Hanno Riess, Claus Rödel, Josef Rüschoff, Wolff Schmiegel, Hans-Joachim Schmoll, Udo Vanhoefer
  Onkologie 01/2011; 34 Suppl 3:1-31. · 0.87 Impact Factor
• Article: Adjuvant therapy of pancreatic cancer.

  Andreas Hilbig, Helmut Oettle
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  ABSTRACT: Pancreatic adenocarcinoma is one of the most aggressive tumors, with a high potential for early dissemination and a relatively poor sensitivity to radiation therapy and cytotoxic agents. Complete resection of the tumor is currently the only curative option but only 10-15% of patients present with localized, potentially resectable disease at the time of diagnosis. Median overall survival for all resected patients (R0 and R1) averages between 11 and 23 months, 5-year overall survival ranges from 10 to 25% (R0) and 0 to 5% (R1), leading to a case-fatality index of 95%. Despite the latest trend toward adjuvant chemotherapy with gemcitabine due to the results from the Charité Onkologie-001 trial, there is no broad consensus regarding the adjuvant regimen that should be applied. Early data from the European Study Group for Pancreatic Cancer-3(v2) trial revealed no difference in terms of overall survival between 5-fluorouracil/folinic acid and gemcitabine after resection of pancreatic cancer.
  Expert Review of Anti-infective Therapy 04/2010; 10(4):485-91. · 2.65 Impact Factor
• Article: Mutational analysis of K-ras codon 12 in blood samples of patients with acute myeloid leukemia.

  Roman Preston, Jan Däbritz, Joachim Hänfler, Helmut Oettle
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  ABSTRACT: Mutations in K-ras are frequent in acute myeloid leukemia (AML). The association of these mutations to clinical features and their prognostic value are unclear. We used quantitative PCR with peptide nucleic acid mediated PCR clamping to specifically analyze 257 blood samples of 31 AML patients for K-ras codon 12 alterations. A total of 20 samples of nine patients harbored a K-ras mutation. The most frequent mutation was the GTT variant which causes an amino acid exchange from glycine to valine. Correlation with clinical data suggests K-ras mutations to be associated with higher age and a better response to anti-leukemic chemotherapy.
  Leukemia research 03/2010; 34(7):883-91. · 2.36 Impact Factor
• Source

  Available from: Mehmet Gövercin

  Article: Parenteral nutrition support for patients with pancreatic cancer. Results of a phase II study.

  Uwe Pelzer, Dirk Arnold, Mehmet Gövercin, Jens Stieler, Bernd Doerken, Hanno Riess, Helmut Oettle
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  ABSTRACT: Cachexia is a common problem in patients (pts) suffering from upper gastrointestinal cancer. In addition, most of these patients suffer from malabsorption and stenosis of the gastrointestinal tract due to their illness. Various methods of supplementary nutrition (enteral, parenteral) are practised. In patients with advanced pancreatic cancer (APC), phase angle, determined by bio-electrical impedance analysis (BIA), seems to be a survival predictor. The positive influence of BIA determinate predictors by additional nutrition is currently under discussion. To examine the impact of additional parenteral nutrition (APN) we assessed outpatients suffering from APC and progressive cachexia. The assessment based on the BIA method. Assessment parameters were phase angle, ECM/BCM index (ratio of extracellular mass to body cell mass), and BMI (body mass index). Patients suffering from progressive weight loss in spite of additional enteral nutritional support were eligible for the study. Median treatment duration in 32 pts was 18 [8-35] weeks. Response evaluation showed a benefit in 27 pts (84%) in at least one parameter. 14 pts (43.7%) improved or stabilised in all three parameters. The median ECM/BCM index was 1.7 [1.11-3.14] at start of APN and improved down to 1.5 [1.12-3.36] during therapy. The median BMI increased from 19.7 [14.4-25.9] to 20.5 [15.4-25.0]. The median phase angle improved by 10% from 3.6 [2.3-5.1] to 3.9 [2.2-5.1]. We demonstrated the positive impact of APN on the assessed parameters, first of all the phase angle, and we observed at least a temporary benefit or stabilisation of the nutritional status in the majority of the investigated patients. Based on these findings we are currently investigating the impact of APN on survival in a larger patient cohort. ClinicalTrials.gov Identifier: NCT00919659.
  BMC Cancer 03/2010; 10:86. · 3.01 Impact Factor
• Article: [New data on pancreatic cancer].

  Rainer Fietkau, Volker Heinemann, Helmut Oettle, Wolfram Trudo Knoefel, Andrea Tannapfel
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  ABSTRACT: In pancreatic cancer there is a marked discrepancy between the recorded R0 resection rates and the long-term clinical outcome. Therefore, it seems to be necessary to find additional parameters that will be of more prognostic value here. Differences in how the R classification is applied within the studies are conspicuous. It would seem important to examine standards in histopathological preparation and to return to the 'classical' R classification and, if appropriate, in line with experiences in rectum cancer, to introduce a 'circumferential resection margin'. To obtain optimum long-term survival, a distance of >1.0 mm or even >1.5 mm between tumor and resection margin is required. In too few patients with vascular invasion is the tumor properly removed surgically, even though infiltration of the portal vein or the superior mesenteric vein is not an exclusion criterion according to the S3 guideline. An improvement in the quality of treatment might be achieved by establishing 'high-volume' pancreas centers. The value of perioperative radiochemotherapy (RCT) is currently being examined in several large studies. Adjuvant chemotherapy is standard and is well established in routine clinical practice.
  Onkologie 01/2010; 33 Suppl 4:31-5. · 0.87 Impact Factor
• Article: Second-line therapy in refractory pancreatic cancer. results of a phase II study.

  Uwe Pelzer, Jens Stieler, Lars Roll, Andreas Hilbig, Bernd Dörken, Hanno Riess, Helmut Oettle
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  ABSTRACT: This phase II trial investigated the efficacy and safety of oxaliplatin (O), 5-fluorouracil (5-FU), and folinic acid (FA) (OFF) as second-line treatment for patients with metastatic pancreatic adenocarcinoma after failure of first-line gemcitabine treatment. 37 patients with confirmed progressive disease on gemcitabine therapy were treated with OFF (O 85 mg/m(2) days 8, 22; FA 500 mg/m(2), followed by 5-FU 2,600 mg/m(2) days 1, 8, 15, 22) every 6 weeks. Patients were treated on an outpatient basis and remained on treatment until disease progression. All patients were assessable for toxicity and effectiveness. We observed moderate hematotoxicity, the most common non-hematologic toxicity was neurotoxicity. A total of 12 patients had grade 3 nonhematologic toxicities: nausea and vomiting (4 patients), reversible neurotoxicity (5 patients), and diarrhea (3 patients). No grade 4 toxicities were observed. Median time to progression was 12 (1-125) weeks. Survival in second line was 22 (4-326+) weeks. Overall disease control rate was 49% (complete remission = 3%; partial remission = 3%; stable disease > 12 weeks = 43%). This regimen is feasible and active with an acceptable toxicity profile; it can be safely administered in an outpatient setting. There is an urgent need for further investigation in phase III trials.
  Onkologie 03/2009; 32(3):99-102. · 0.87 Impact Factor
• Article: Follow-up study of K-ras mutations in the plasma of patients with pancreatic cancer: correlation with clinical features and carbohydrate antigen 19-9.

  Jan Däbritz, Roman Preston, Joachim Hänfler, Helmut Oettle
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  ABSTRACT: We followed up the presence of Kirsten rat sarcoma (K-ras) mutations in plasma DNA and assessed its clinical value in patients with pancreatic cancer. Plasma samples (N = 430) of 56 patients with pancreatic cancer and 13 patients with pancreatitis were analyzed by real-time polymerase chain reaction using peptide nucleic acid-mediated polymerase chain reaction clamping. K-ras mutations could be detected in the plasma DNA of 20 patients with cancer (36%). No K-ras mutation was found in the plasma of patients with pancreatitis. In 7 (35%) of 20 patients with lowly or moderately elevated carbohydrate antigen 19.9 (CA 19-9) levels lower than 100 U/mL, the result of the assay was positive for K-ras mutation. The combination of K-ras and CA 19-9 level determination gave a sensitivity for the diagnosis of pancreatic cancer of 91% (40/44) of the patients. Thirteen of 35 patients with pancreatic cancer (102 plasma samples) with elevated CA 19-9 levels (>35 U/mL) and altered K-ras gene showed significant correlation with elevated CA 19-9 levels (P=0.048). The summary of our approach of noninvasive, convenient, extremely high-sensitive K-ras mutation analysis in plasma might provide diagnostic and prognostic information to clinicians but will not be sufficient in a standardized early diagnosis of pancreatic carcinoma. The combination with CA 19-9 assay is useful for detection and prognostic evaluation of pancreatic carcinoma.
  Pancreas 03/2009; 38(5):534-41. · 2.39 Impact Factor
• Article: [Diagnosis and treatment of liver metastases from primary colorectal tumour].

  Dirk Arnold, Ernst J Rummeny, Thomas Kirchner, Karsten Ridwelski, Helmut Oettle, Jörg Thomas Hartmann, Markus Moehler, Arnulf Hölscher, Hauke Lang, Hans J Schlitt, Peter Neuhaus
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  ABSTRACT: Contrast-enhanced multislice computer tomography (MSCT) has established itself as the standard tomographic imaging method both for diagnosis and for treatment monitoring of hepatic lesions. To clarify local conditions before partial liver resection, diffusion-weighted magnetic resonance tomography (DWI-MRT) can also provide important additional information. In order to meet the criteria for a R0 resection, a margin of 0.5 mm seems to be sufficient. Neoadjuvant chemotherapy aiming to reduce tumour size can be given in parallel with portal artery embolisation without adversely affecting perioperative morbidity and mortality. As far as the management of primary resectable liver metastases is concerned, there is an urgent need for more studies. Despite the relatively limited evidence, adjuvant chemotherapy is currently more widely favoured in Germany than perioperative chemotherapy. There is also considerable need for studies concerning preoperative therapy in patients with liver metastases that are not (yet) resectable. In KRAS wild-type tumours, high response rates (in terms of a reduction in the size of metastases) are achieved with a cetuximab/chemotherapy combination. Bevacizumab/chemotherapy combinations lead to high rates of pathohistological complete and partial remissions. What the best parameter for judging the success of preoperative therapy is remains unknown, and so comparison studies using survival as a 'hard' endpoint must be carried out.
  Onkologie 02/2009; 32 Suppl 2:7-12. · 0.87 Impact Factor
• Source

  Available from: Uwe Pelzer

  Article: Rationale and design of PROSPECT-CONKO 004: a prospective, randomized trial of simultaneous pancreatic cancer treatment with enoxaparin and chemotherapy).

  Hanno Riess, Uwe Pelzer, Andreas Hilbig, Jens Stieler, Bernhard Opitz, Theo Scholten, Dörte Kauschat-Brüning, Peter Bramlage, Bernd Dörken, Helmut Oettle
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  ABSTRACT: Advanced pancreatic cancer, in addition to its high mortality, is characterized by one of the highest rates of venous thromboembolic events (VTE) as compared to other types of cancer. Enoxaparin, a low molecular weight heparin (LMWH), has proven to be effective for the prevention and treatment of VTE in surgical and general medical patients. Results of some small studies suggest that this benefit might extend to patients with cancer, however, enoxaparin is not currently indicated for this use. This phase IIb study was designed to analyze the efficacy of enoxaparin in patients with locally advanced or metastatic pancreatic cancer undergoing systemic chemotherapy. The aim of this prospective multicenter trial is to compare concomitant treatment with enoxaparin to no anticoagulation in 540 patients. Primary endpoint is the incidence of clinically relevant VTE (symptomatic deep venous thrombosis (DVT) of the leg and/or pelvic and/or pulmonary embolism (PE)) within the first 3 months. Secondary endpoints include the incidence of symptomatic and asymptomatic VTE after 6, 9 and 12 months as well as remission at 3, 6, 9 and 12 months, overall survival and bleeding. Trial registration: isrctn.org identifier CCT-NAPN-16752, controlled-trials.com identifier: ISRCTN02140505. An interim analysis for safety performed after inclusion of 152 patients revealed no increased risk of bleeding (5 pts vs. 6 pts, Chi2: 0.763). PROSPECT is a pivotal study in elucidating the role of low molecular weight heparins in advanced pancreatic cancer. Its results will lead to a new understanding of the role of heparins in the prevention of venous thromboembolism and of their effect on survival, remission rates and toxicity of chemotherapeutic regimens.
  BMC Cancer 01/2009; 8:361. · 3.01 Impact Factor
• Article: Gemcitabine in the treatment of metastatic pancreatic cancer.

  Andreas Hilbig, Helmut Oettle
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  ABSTRACT: Gemcitabine (2 ,2 -difluorodeoxycytidine) is a deoxycytidine-analog antimetabolite with broad activity against a variety of solid tumors and lymphoid malignancies. It was approved as standard of care in patients with pancreatic cancer one decade ago, based primarily on improvement in clinical benefit response such as pain reduction, improvement in Karnofsky performance status and increase in body weight. This article gives an overview of the pharmacodynamics and pharmacokinetics of gemcitabine, highlights the clinical activity of gemcitabine and summarizes the treatment options in metastatic pancreatic cancer with focus on gemcitabine-based chemotherapy. The emerging role of combinations of gemcitabine with novel targeted agents, including small-molecule inhibitors and other investigational drugs, is also discussed.
  Expert Review of Anti-infective Therapy 05/2008; 8(4):511-23. · 2.65 Impact Factor
• Article: Does the addition of erlotinib to gemcitabine improve outcome in patients with advanced pancreatic cancer?

  Helmut Oettle, Andreas Hilbig
  Nature Clinical Practice Oncology 01/2008; 4(12):686-7. · 8.00 Impact Factor
• Article: [Treatment of advanced pancreatic carcinoma].

  Thomas Höhler, Ludger Staib, Helmut Oettle
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  ABSTRACT: Gemcitabine monotherapy extends survival times in locally advanced or metastatic pancreatic carcinoma compared with supportive treatment alone. Among patients who develop skin lesions of grade 2 or more, giving erlotinib in addition doubles survival times - from 5.9 to 10.5 months. Attempting therapy with gemcitabine plus erlotinib is therefore sensible. In patients with a good performance status, survival times can be extended using the combinations gemcitabine plus capecitabine or gemcitabine plus platinum. Radiochemotherapy is not sensible. For second-line treatment, oxaliplatin, 5-FU, and folic acid can be used.
  Onkologie 01/2008; 31 Suppl 5:29-31. · 0.87 Impact Factor
• Chapter: Immunotherapeutic Approaches in Pancreatic Cancer

  Jens Stieler, Hanno Riess, Andrea Goerke, Helmut Oettle
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  ABSTRACT: With growing understanding of the regulation of immune responses, multiple new immunotherapeutic targets have evolved. This article gives a survey over the current approaches in pancreatic cancer therapy including peptide vaccinations, unspecific immunotherapy, allogene modified tumor cell vaccines, and vector-based vaccines. Although several trials have shown detectable immune responses, such as delayed-type hypersensitivity reactions and cytokine release in enzyme- linked immunosorbent spot (ELISPOTS) assays, and some have reported prolonged survival for immune responders, immunotherapy remains experimental. However, some approaches have made it into a phase III setting. In addition, the emerging concept of tumor stem cells may lead to a new focus on immunotherapy, since these often highly chemotherapy-resistant cells are thought to be the source of recurrences.
  12/2007: pages 165-177;
• Chapter: Detection of Disease Recurrence and Monitoring of Therapy

  Juri Ruf, Holger Amthauer, Hanno Riess, Andrea Goerke, Helmut Oettle
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  ABSTRACT: The detection of disease recurrence and treatment monitoring pose high demands on diagnostic modalities. Whereas serum marker levels in most cases allow an assessment of tumor load and a respective response to therapy, they do not confer information on the localization of disease. Although this diagnostic gap is filled by imaging modalities, most techniques based on morphology will come to a limit when fibrotic tissue alterations have to be differentiated from viable tumor tissue in case of suspected recurrence or when residual masses after chemotherapy have to be assessed. The metabolic information on tumor cells gained by fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging appears not only to be more sensitive and reliable in this respect, but also appears to allow assumptions on response to therapy, and ultimately on patient prognosis.
  12/2007: pages 105-110;
• Chapter: Neoadjuvant and Adjuvant Strategies for Chemoradiation

  Andreas Kaiser, Volker Budach, Hanno Riess, Andrea Goerke, Helmut Oettle
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  ABSTRACT: There is an increasing body of evidence showing that patients with resectable pancreatic cancer might benefit from adjuvant therapy. Based on phase III trials, potential options for adjuvant treatment are chemotherapy alone or a multimodal approach involving radiotherapy. Available data are heterogeneous and have been discussed controversially. Hitherto, a worldwide standard of care has not yet been established. Adequate patient selection might be the key element for a tailored adjuvant treatment. Clinical research currently focusses on gemcitabine alone or in combination, and some molecular biologic approaches with epidermal growth factor receptor monoclonal antibodies (EGFR-MoABs) and anti-angiogenic drugs. Recent advances in radiooncology offer better dose conformality and reduced morbidities. Currently, the co-operative Radiotherapy and Gastrointestinal Groups have launched a multicentric European Organization for Research and Treatment of Cancer (EORTC) trial investigating the impact of radiotherapy in combination with gemcitabine in R0-resected pancreatic head cancer.
  12/2007: pages 65-77;
• Chapter: Nuclear Medical Methods for the Diagnosis of Pancreatic Cancer: Positron Emission Tomography

  Holger Amthauer, Juri Ruf, Hanno Riess, Andrea Goerke, Helmut Oettle
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  ABSTRACT: The functional imaging approach of nuclear medicine offers important information for the characterization of a tumor‘s pathobiology. In oncology, positron emission tomography (PET) especially has had great impact on the staging of tumor patients and the assessment of therapy. Both the development of new, tumor-specific, tracers and the introduction of by software- and hardware-driven image fusion emphasize the potential of this modality for an all-embracing diagnostic modality.
  12/2007: pages 15-26;