Wimberger P.,University of Duisburg - Essen |
Gilet H.,Mapi Consultancy |
Gonschior A-K.,Fresenius Biotech GmbH |
Heiss M.M.,Cologne Merheim Medical Center |
And 7 more authors.
Annals of Oncology | Year: 2012
Background: Malignant ascites (MA) is associated with poor prognosis and limited palliative therapeutic options. Therefore, quality of life (QoL) assessment is of particular importance to demonstrate new treatment value. Following the demonstration of the superiority of catumaxomab and paracentesis over paracentesis on puncture-free survival, this analysis aimed at comparing deterioration in QoL between both the treatment options. Patients and methods: In a randomised, multicentre, phase II/III study of patients with MA due to epithelial cell adhesion molecule (EpCAM) positive cancer, the QoL was evaluated using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 items (EORTC QLQ-C30) questionnaire at screening, 1, 3 and 7 months after treatment and in the case of re-puncture on the day of paracentesis. Time to first deterioration in QoL was defined as a decrease in the QoL score of at least five points and compared between the catumaxomab (n = 160) and control (n = 85) groups using the log-rank test and Cox proportional hazards models adjusted for baseline score, country and primary tumour type. Results: Deterioration in QoL scores appeared more rapidly in the control than in the catumaxomab group (median 19-26 days versus 47-49 days). The difference in time to deterioration in QoL between the groups was statistically significant for all scores (P < 0.01). The hazard ratios ranged from 0.08 to 0.24 (P < 0.01). Conclusions: Treatment with catumaxomab delayed deterioration in QoL in patients with MA. Compared with paracentesis alone, catumaxomab enabled patients to benefit from better QoL for a prolonged survival period. © The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: An open-label, multicentre, randomised, phase 3 non-inferiority trial
Rummel M.J.,Justus Liebig University |
Niederle N.,Klinikum Leverkusen |
Maschmeyer G.,Ernst von Bergmann Klinikum |
Banat G.A.,Justus Liebig University |
And 16 more authors.
The Lancet | Year: 2013
Background: Rituximab plus chemotherapy, most often CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), is the first-line standard of care for patients with advanced indolent lymphoma, and for elderly patients with mantle-cell lymphoma. Bendamustine plus rituximab is effective for relapsed or refractory disease. We compared bendamustine plus rituximab with CHOP plus rituximab (R-CHOP) as first-line treatment for patients with indolent and mantle-cell lymphomas. Methods: We did a prospective, multicentre, randomised, open-label, non-inferiority trial at 81 centres in Germany between Sept 1, 2003, and Aug 31, 2008. Patients aged 18 years or older with a WHO performance status of 2 or less were eligible if they had newly diagnosed stage III or IV indolent or mantle-cell lymphoma. Patients were stratified by histological lymphoma subtype, then randomly assigned according to a prespecified randomisation list to receive either intravenous bendamustine (90 mg/m2 on days 1 and 2 of a 4-week cycle) or CHOP (cycles every 3 weeks of cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and vincristine 1·4 mg/m2 on day 1, and prednisone 100 mg/day for 5 days) for a maximum of six cycles. Patients in both groups received rituximab 375 mg/m2 on day 1 of each cycle. Patients and treating physicians were not masked to treatment allocation. The primary endpoint was progression-free survival, with a non-inferiority margin of 10%. Analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00991211, and the Federal Institute for Drugs and Medical Devices of Germany, BfArM 4021335. Findings: 274 patients were assigned to bendamustine plus rituximab (261 assessed) and 275 to R-CHOP (253 assessed). At median follow-up of 45 months (IQR 25-57), median progression-free survival was significantly longer in the bendamustine plus rituximab group than in the R-CHOP group (69·5 months [26·1 to not yet reached] vs 31·2 months [15·2-65·7]; hazard ratio 0·58, 95% CI 0·44-0·74; p<0·0001). Bendamustine plus rituximab was better tolerated than R-CHOP, with lower rates of alopecia (0 patients vs 245 (100%) of 245 patients who recieved ≥3 cycles; p<0·0001), haematological toxicity (77 [30%] vs 173 [68%]; p<0·0001), infections (96 [37%] vs 127 [50%]); p=0·0025), peripheral neuropathy (18 [7%] vs 73 [29%]; p<0·0001), and stomatitis (16 [6%] vs 47 [19%]; p<0·0001). Erythematous skin reactions were more common in patients in the bendamustine plus rituximab group than in those in the R-CHOP group (42 [16%] vs 23 [9%]; p=0·024). Interpretation: In patients with previously untreated indolent lymphoma, bendamustine plus rituximab can be considered as a preferred first-line treatment approach to R-CHOP because of increased progression-free survival and fewer toxic effects. Funding: Roche Pharma AG, Ribosepharm/Mundipharma GmbH.
Effects of zoledronic acid versus placebo on bone mineral density and bone texture analysis assessed by the trabecular bone score in premenopausal women with breast cancer treatment-induced bone loss: results of the ProBONE II substudy
Kalder M.,University of Marburg |
Kyvernitakis I.,University of Marburg |
Albert U.S.,Krankenhaus Nordwest |
Baier-Ebert M.,Novartis |
Hadji P.,Endocrinology and Reproductive Medicine
Osteoporosis International | Year: 2014
Summary: Changes in bone mineral density (BMD) and trabecular bone score (TBS) were assessed in 70 patients who received either zoledronate (ZOL) (n = 34) or placebo (n = 36) for 2 years. In premenopausal women with breast cancer treatment-induced bone loss, 24 months of intravenous ZOL treatment significantly increased the lumbar spine BMD and the TBS.Introduction: The aim of this study was to compare the effects of 4 mg intravenous zoledronate (ZOL) versus placebo (PLB), every 3 months, on the lumbar spine (LS) bone mineral density (BMD) and the trabecular bone score (TBS) in premenopausal women with breast cancer (BC) treatment-induced bone loss. The TBS is a gray-level texture measurement which is related to the bone microarchitecture and considered to be independent of the BMD.Methods: Changes in BMD and TBS were assessed in 70 patients who were recruited in the double-blind, placebo-controlled ProBONE-II trial and randomized to receive either ZOL (n = 34) or PLB (n = 36) for 2 years. The changes were assessed at baseline and at 12 and 24 months after treatment initiation.Conclusions: In premenopausal women with BC, 24 months of intravenous ZOL treatment significantly increased the LS BMD as well as the TBS.Results: Patients receiving ZOL showed a mean increase in LS BMD from the baseline to 12 (2.17 %) and 24 months (3.14 %) of treatment and a mean increase in the TBS of 2.41 and 0.75 %, respectively. Conversely, patients receiving PLB showed a mean decrease in the LS BMD from the baseline to 12 (−5.02 %) and 24 (−6.43 %) months and a mean decrease of −0.52 and −2.16 % in the TBS, respectively. Changes in the BMD and the TBS from the baseline to 12 and 24 months were all significantly different for ZOL compared to PLB (p < 0.005). Furthermore, BMD and TBS showed a moderate correlation ranging from 0.28 (p = 0.087) to 0.47 (p = 0.003). © 2014, International Osteoporosis Foundation and National Osteoporosis Foundation.
Jacke C.O.,University of Heidelberg |
Albert U.S.,Krankenhaus Nordwest |
Reinhard I.,University of Heidelberg |
Kalder M.,University of Marburg
Journal of Cancer Research and Clinical Oncology | Year: 2015
Purpose: To benchmark outcomes of a German breast cancer network with the Surveillance Epidemiology and End Results programme (SEER) of the USA from a longitudinal point of view.Methods: All women receiving primary breast cancer therapy of three hospitals in a rural district of Marburg-Biedenkopf (Germany) of time intervals 1996–1997 and 2003–2004 were used to define local benchmark objects. Data from SEER-programme contributed longitudinal benchmark objects from national level (1988–2004). All benchmark objects were compared with the time-fixed benchmark reference of SEER (2004). Stage distributions and 5-year relative survival ratios were combined to estimate standardized screening-, case-mix-, work-up-, treatment- and relative overall performance index.Results: From the entry cohort of 877 German women, 97.7 % of the patients accounted for the institutional sample (N = 857) and 65.8 % accounted for the regional sample (N = 577). Stage distributions, relative survival ratios and indices of the German breast cancer network improved over time. Developed indices converged with SEER (2004).Conclusions: Effectiveness gap between one exemplary German breast cancer network and international benchmark defined by SEER has been closed. Reasons are manifold, and further research is recommended. © 2014, Springer-Verlag Berlin Heidelberg.
Hofheinz R.-D.,University of Heidelberg |
Al-Batran S.-E.,Krankenhaus Nordwest |
Hochhaus A.,University of Heidelberg |
Hochhaus A.,Universitatsklinikum Jena |
And 5 more authors.
Clinical Cancer Research | Year: 2010
Purpose: This phase I, open-label, dose-escalation study investigated the maximum tolerated dose (MTD) of BI 2536, a small-molecule polo-like kinase (Plk)-1 inhibitor, in two treatment schedules in patients with advanced solid tumors. Secondary objectives included evaluation of safety, efficacy, and pharmacokinetics. Experimental Design: Patients received a single i.v. dose of BI 2536 as a 1-hour infusion on days 1 and 8 or a single 24-hour infusion on day 1 of each 21-day treatment course. MTD determination was based on dose-limiting toxicities. Results: Forty-four and 26 patients received each treatment schedule, respectively. The MTD of BI 2536 in the day 1 and 8 schedule was 100 mg per administration (200 mg per course). The MTD for the second dosing schedule was not determined; a 225-mg dose was well tolerated. The most frequently reported treatment-related nonhematologic adverse events were gastrointestinal events and fatigue. Hematotoxicity as the most relevant side effect was similar in both schedules; neutropenia grades 3 and 4 were observed in 16 patients (36.4%) of the day 1 and 8 schedule and 13 patients (50%) of the 24-hour infusion. Fourteen patients (32%) treated in the day 1 and 8 dosing schedule had a best overall response of stable disease. Plasma concentrations of BI 2536 increased dose proportionally, with no relevant accumulation of exposure in the day 1 and 8 dosing schedule. The average terminal half-life was 50 hours. Conclusions: BI 2536 administered in either treatment schedule has adequate safety in patients with advanced solid tumors, warranting further clinical investigation of polo-like kinase-1 inhibitors. ©2010 AACR.
Janjigian Y.Y.,Sloan Kettering Cancer Center |
Werner D.,University Cancer Center |
Pauligk C.,University Cancer Center |
Steinmetz K.,University Cancer Center |
And 8 more authors.
Annals of Oncology | Year: 2012
Background: To determine whether human epidermal growth factor receptor 2 (HER2) status is an independent prognostic factor in metastatic gastric and gastroesophageal junction (GEJ) adenocarcinoma. Patients and methods: Formalin-fixed paraffin-embedded tumor samples from 381 metastatic gastric/GEJ cancer patients enrolled at Krankenhaus Nordwest and Memorial Sloan-Kettering Cancer Centers on six first-line trials of chemotherapy without trastuzumab were examined for HER2 by immunohistochemistry (IHC) and in situ hybridization (ISH). IHC 3+ or ISH-positive tumors were considered HER2 positive. Results: Seventy-eight of 381 patients (20%) had HER2-positive disease. In the multivariate logistic model, there were significantly higher rates of HER2 positivity in patients with liver metastasis (liver metastasis 31%; no liver metastasis 11%; P = 0.025) and intestinal histology (intestinal 33%; diffuse/mixed 8%; P = 0.001). No significant differences in HER2 positivity were found between resections and biopsies or primaries and metastases. Patients with HER2-positive gastric cancer had longer median overall survival compared with HER2-negative gastric cancer patients (13.9 versus 11.4 months, P = 0.047), but multivariate analysis indicated that HER2 status was not an independent prognostic factor (hazard ratio 0.79; 0.44-1.14; P = 0.194). Conclusions: Approximately 20% of Western patients with metastatic gastric cancer are HER2 positive. Unlike breast cancer, HER2 positivity is not independently prognostic of patient outcome in metastatic gastric or GEJ. © The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
Al-Batran S.-E.,Krankenhaus Nordwest |
Ducreux M.,Institute Gustave Roussy |
Ohtsu A.,National Cancer Center Hospital East
International Journal of Cancer | Year: 2012
The poor long-term outcomes associated with current chemotherapy treatment of patients with advanced gastric cancer suggest a need for novel targeted agents that may confer a better survival benefit. Evidence of mammalian target of rapamycin (mTOR) activation has been demonstrated in patient-derived gastric cancer cells and tumors. This review explores the relevance of the mTOR pathway to gastric cancer pathogenesis and its potential as a therapeutic target in patients with gastric cancer as well as presenting the first available clinical data on mTOR inhibitors in this disease setting. Preclinical data suggest that suppression of the mTOR pathway inhibited the proliferation of gastric cancer cells and delayed tumor progression in in vitro and animal models. In the clinical setting, the mTOR inhibitor everolimus has been active and well tolerated in phase I/II studies of patients with chemotherapy-refractory metastatic gastric cancer. Based on these promising results, everolimus currently is being investigated as a monotherapy or in combination with chemotherapeutic agents in ongoing phase II/III clinical studies. Copyright © 2011 UICC.
Bjerklund Johansen T.E.,Aarhus University Hospital |
Witzsch U.,Krankenhaus Nordwest |
Greene D.,University of Sunderland
Expert Review of Anticancer Therapy | Year: 2013
Radiotherapy is the main salvage option after primary radical prostatectomy. Radical prostatectomy, cryosurgical ablation and high-intensity focused ultrasound are the main salvage options after primary radiotherapy. After primary radiotherapy, long-term oncological outcome of salvage radical prostatectomy and salvage cryosurgical ablation is fairly comparable with the results of primary radical prostatectomy and primary cryosurgical ablation. Side effects of salvage radical prostatectomy in elite centers are acceptable and side effects of salvage cryosurgical ablation in tertiary centers are almost the same as after primary cryosurgical ablation. Good long-term data after salvage high-intensity focused ultrasound are lacking and the risk of side effects is considerable. After primary radical prostatectomy, there is a high level of evidence for oncological benefit of salvage radiotherapy. Careful patient selection is important for all salvage modalities. © 2013 2013 Expert Reviews Ltd.
Meyding-Lamade U.,Krankenhaus Nordwest |
Strank C.,Krankenhaus Nordwest
Therapeutic Advances in Neurological Disorders | Year: 2012
Human herpesviruses may cause infections of the central nervous system during primary infection or following reactivation from a latent state. Especially in immunosuppressed patients the infection can take a life-threatening course, and therefore early diagnosis of herpesvirus-associated neurological diseases should have high priority. Clinical presentation in these patients is usually without typical features, making diagnosis even more challenging. Therefore general broad testing for different herpesviruses in cerebrospinal fluid samples is highly recommended. In addition, determination of the virus DNA level in the cerebrospinal fluid by quantitative assays seems to be of high importance to determine prognosis. Moreover, it might help to differentiate between specific virus-associated disease and unspecific presence of virus in the cerebrospinal fluid, especially in immunocompromised patients. Polymerase chain reaction analysis of cerebrospinal fluid has revolutionized the diagnosis of nervous system viral infections, particularly those caused by human herpesviruses. This review summarizes the role human herpesviruses play in central nervous system infections in immunocompromised patients, with a focus on the clinical manifestation of encephalitis. © 2012 The Author(s).
Schmidt K.,Goethe University Frankfurt |
Vogt L.,Goethe University Frankfurt |
Thiel C.,Goethe University Frankfurt |
Jager E.,Krankenhaus Nordwest |
Banzer W.,Goethe University Frankfurt
International Journal of Sports Medicine | Year: 2013
The present study evaluated the validity of the six-minute walk test (6MWT) in cancer patients. 50 subjects (36 f, 14 m; 57.4±10.2 years; during (56%) or off (44%) cancer treatment) performed a 6MWT and a spiroergometry on a cycle ergometer (0+25 W, 3 min) to evaluate maximum exercise capacity (VO 2peak). A subsample (n=30) completed a retest of the 6MWT within 2-7 days. Patients covered a distance of 594±81 m during 6MWT at an average intensity of 86.3±9.6% of HRmax and achieved a VO 2peak of 21.2±4.86 ml · kg-1 · min-1 during cycle ergometry. The distance walked correlated significantly (p<0.001) with VO2peak (r=0.67) and perceived physical function (EORTC QLQ-C30 physical function subscale) (r=0.55). Concerning reliability the intraclass correlation coefficient was r=0.93 (95%CI: +0.86;+0.97; p<0.001) and the coefficient of variation 3%. During retest participants walked 3.1% (95%CI: +1.1; +5.2) farther and achieved a higher RPE (+1.0; 95%CI: +0.3;+1.8). Limits of agreement were between - 43.1 and 76.4 m. In cancer patients the 6MWT seems to be as valid and reliable as in healthy elderly, cardiac and pulmonary patients. Thus, it can be recommended for use in cancer patients. © Georg Thieme Verlag KG Stuttgart • New York.