Clinical studies have been situated very well in Germany during the last 10 years; oncologists in practices and clinics are highly motivated. However, the financing of clinical trials is desolate so that disillusionment...Clinical studies have been situated very well in Germany during the last 10 years; oncologists in practices and clinics are highly motivated. However, the financing of clinical trials is desolate so that disillusionment spreads in many centers. This paper would like to give some impetus to the discussion on better and more adequate financing. Facts and backgrounds concerning unsatisfactory financing of clinical trials are demonstrated; costs are analyzed in a detailed way. It seems to be very important to establish tools for a better calculation of costs. First approaches have been defined.
Academic non-commercial trials are of substantial relevance for both patient care and progress in clinical research. Since the 12th amendment of the German drug law, applications for the initiation of clinical trials at...Academic non-commercial trials are of substantial relevance for both patient care and progress in clinical research. Since the 12th amendment of the German drug law, applications for the initiation of clinical trials at the ethical review boards are much more cost- and time-intensive, particularly for multicenter therapy optimization trials (TOS). To activate a trial, for, e.g., 51 ethical review boards, current curricula vitae (CVs) and certificates on good clinical practice (GCP) and regulations have to be provided for all investigators. After the new amendment of the German drug law in 2012, the process remains complex while the responsibility of the team eligibility has now been transferred to the main investigator at the study site. Therefore, the online database 'QualiPRO' was developed, free of charge and widely accessible for the investigators, their clinical trial units and the coordinating centers of the TOS. Its features ease the process to generate and provide data on the clinical trial activities of any investigator and team member. The database content and architecture follows ethical review board recommendations and the Good Clinical Practice (GCP) of the International Conference on Harmonisation (ICH). After registration of the unit and membership of the team, study staff' members are able to enter and edit data and to print a 'trial' CV. CVs, GCP certificates, licences to practice medicine and more can be uploaded, and, after consent of the investigators, are available to the coordinating centers of TOS. In addition, QualiPRO is an instrument for directors of hospital departments or group leaders to efficiently collect and locally display data on their study activities and on the training status of their staff.
Before the start of a clinical trial, approval by the responsible institutional ethical review board (IRB) is required. In Germany, nearly 50 independent IRBs may be responsible for the different participating sites of a...Before the start of a clinical trial, approval by the responsible institutional ethical review board (IRB) is required. In Germany, nearly 50 independent IRBs may be responsible for the different participating sites of a multicenter study. In trials for rare diseases, the participation of many centers is required. Therefore, the application procedure for academic multicenter trials in malignant hematologic diseases is often a bureaucratic nightmare. Different aspects of IRB application and possible approaches for improvement are presented.
BACKGROUND: The purpose of this study was to evaluate the effect of legal regulations for clinical trials on study centers participating in investigator-initiated trials (IITs) in the field of hematology/oncology. METHOD...BACKGROUND: The purpose of this study was to evaluate the effect of legal regulations for clinical trials on study centers participating in investigator-initiated trials (IITs) in the field of hematology/oncology. METHOD: Questionnaires were sent out to the heads of hematology-oncology study centers. RESULTS: Medical units participating in IITs have a good infrastructure and extensive experience in clinical trials. Depending on indication, a high proportion of patients have been treated in studies with the purpose to improve outcome. However, 35% of the responders will reduce their participation in IITs in the future due to a lack of financial support for staff involved in the extensive organizational tasks. CONCLUSIONS: The widely recognized research field in therapy optimization trials in hematology and oncology in Germany is at risk. This will have negative effects on the patients as highly sophisticated protocols will no longer be initiated in several study centers, resulting in the loss of valuable data for the improvement of patient therapy and outcome. To stop this development, legislators as well as regulatory authorities and health insurances need to make the necessary changes in the legal framework.
The market authorisation or extension of indication for all oncology drugs in Europe is now based on Regulation (EC) No. 726/2004, a centralised procedure of the European Medicines Agency (EMA). Studies in recent years h...The market authorisation or extension of indication for all oncology drugs in Europe is now based on Regulation (EC) No. 726/2004, a centralised procedure of the European Medicines Agency (EMA). Studies in recent years have highlighted deficiencies in pivotal studies. For example, the requirements of the EMA are not always consistently followed and studies are stopped prematurely after only interim analysis that at this time point shows improved efficacy with regard to the comparator arm. Our current analysis of the European Assessment Reports (reporting period: 01/01/2009 to 08/13/2012) on 29 drugs for 39 oncology indications shows that the quality of the trials for market authorisation has improved in several respects. Primary endpoints recommended by the EMA and the Food and Drug Administration (FDA) such as overall survival and progression-free survival are used, and only one study was conducted as a phase II trial with no comparator arm. In contrast, oncology drugs that are approved for the treatment of rare diseases (orphan drugs) are based on small studies which are often carried out without blinding, are not randomised and investigate surrogate endpoints. To answer patient-relevant issues following market authorisation, it is necessary to conduct independent clinical studies. Increased public funding needs to be provided and bureaucratic hurdles have to be reduced. Only this will permit a more efficient use of limited health care resources and allow to improve the quality of care for cancer patients.
The results of clinical, preferably randomized controlled trials (RCTs) form the backbone of drug approval decisions and benefit assessments of medical interventions. Whereas drug approval studies often answer at least s...The results of clinical, preferably randomized controlled trials (RCTs) form the backbone of drug approval decisions and benefit assessments of medical interventions. Whereas drug approval studies often answer at least some of the relevant questions posed in a benefit assessment, the situation is totally different for non-drug treatments and diagnostic tests, as the requirements for market entry are not as high in these fields. Overall it must be concluded that in the past and up to the present time there have been insufficient (financial) incentives for manufacturers or providers of medical interventions to conduct clinical trials concerning patient-relevant benefits both in the field of drugs and particularly in non-drug interventions. This has led to a lack of studies that, in an appropriate comparison with sufficient certainty of results, provide data on the patient-relevant benefits or added benefits of a medical intervention. In this context, it is secondary whether these are 'independent' studies, the more so as 'dependencies' can never be excluded and can become especially problematic in cases where they are not easily recognized by declaration of sponsorship. The Institute of Quality and Efficiency in Health Care (IQWiG) is willing to promote the creation of appropriate funding opportunities for important study projects of clinical research groups fulfilling the criteria for a high-quality patient-oriented clinical trial on a relevant research question, and is currently doing so together with interested parties.
Clinical trials connect basic science with patient care. They form the backbone of evidence-based medicine and clinical guidelines. The unprecedented implementation of new methods in oncology over the past 40 years has o...Clinical trials connect basic science with patient care. They form the backbone of evidence-based medicine and clinical guidelines. The unprecedented implementation of new methods in oncology over the past 40 years has only been possible on the basis of multiple well-organized clinical study groups. The continued existence of these study groups in their current multitude is in danger. Far-reaching changes in the legal framework, underfunding, new definitions of patient-related outcome and shifts in the organization of cancer patient care ask for critical reappraisal and new concepts.
Esophageal cancer ranks 8th among the most frequently occurring cancers of the world. The exact cause of esophageal squamous cell carcinoma (ESCC) is unknown; however, some factors like smoking, alcohol intake, consumpti...Esophageal cancer ranks 8th among the most frequently occurring cancers of the world. The exact cause of esophageal squamous cell carcinoma (ESCC) is unknown; however, some factors like smoking, alcohol intake, consumption of fungal-contaminated, spicy, or nitrosamine-containing foodstuffs and hot beverages, together with various genetic factors, have been found associated with the occurrence of this disease in various parts of the world. Much work has been carried out to elucidate the role of various gene mutations and polymorphisms in esophageal mucosal cancer. Previous studies have suggested that esophageal cancer-related gene 1 (ECRG1), as a novel candidate of the tumor suppressor gene family, is expressed in normal esophagus, liver, colon and lung tissues, but the expression is seen to be down-regulated in tumors, especially in ESCC, and in adjacent tissues. The Arg290Gln polymorphism in exon 8 of the ECRG1 gene has been studied in particular in a number of cases and has been observed to play an active role in the development of ESCC. This suggests that substitution of the arginine in the conserved catalytic domain of the ECRG1 protein might reduce its catalytic capacity by impacting its 3-dimensional conformation, thereby causing the genetic susceptibility to ESCC.
BACKGROUND: A Japanese postmarketing survey of panitumumab revealed that panitumumab-associated interstitial lung disease (ILD) occurred in approximately 1% (19/1767) of patients, causing death in 36.8% of these cases. C...BACKGROUND: A Japanese postmarketing survey of panitumumab revealed that panitumumab-associated interstitial lung disease (ILD) occurred in approximately 1% (19/1767) of patients, causing death in 36.8% of these cases. CASE REPORT: We report the case of a 60-year-old Japanese man who developed ILD associated with panitumumab therapy (third-line therapy) for metastatic sigmoid colon cancer involving the liver, lymph nodes, and lungs. 2 months after the initiation of panitumumab therapy, he developed a progressive nonproductive cough, dyspnea, and a fever, and was diagnosed with ILD. Intravenous pulse methylprednisolone treatment led to quick recovery. The patient had some risk factors for ILD associated with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors. CONCLUSION: Further studies are required to elucidate the association between anti-EGFR antibodies and ILD.
BACKGROUND: Many patients with primary myelofibrosis (PMF), a myeloproliferative neoplasm, become transfusion dependent due to anemia. In these patients, transfusion dependency is associated with shortened survival. CASE...BACKGROUND: Many patients with primary myelofibrosis (PMF), a myeloproliferative neoplasm, become transfusion dependent due to anemia. In these patients, transfusion dependency is associated with shortened survival. CASE REPORT: We report on a 67-year-old woman who was diagnosed with PMF. Cytogenetic testing revealed a karyotype 46,XX, del(20)(q11.2), consistent with a myeloproliferative disorder. Although offered to her because of severe anemia and leukocytosis, the patient did not consent to allogeneic hematopoietic stem cell transplantation. After having received a cumulative number of more than 70 packed red blood cell transfusions, iron chelation therapy with deferiprone was initiated to treat iron overload and switched to deferasirox after 3 months. Within 2 months of deferasirox treatment, serum ferritin concentrations were significantly reduced, the patient lost transfusion dependency for 17 months, and normal hemoglobin concentrations were recovered. CONCLUSION: Iron chelation treatment with deferasirox resulted in an improvement of hematologic parameters and loss of transfusion dependency.
INTRODUCTION: Positron emission tomography/computed tomographies (PET/CTs) may result in incidental findings of fluorodeoxyglucose (FDG)-avid lesions in the colon. The aim of this study was to assess the relevance of a c...INTRODUCTION: Positron emission tomography/computed tomographies (PET/CTs) may result in incidental findings of fluorodeoxyglucose (FDG)-avid lesions in the colon. The aim of this study was to assess the relevance of a colonoscopic workup of such lesions. PATIENTS AND METHODS: We retrospectively analysed all PET/CT reports (n = 4,973) generated in our nuclear medicine department between May 2006 and May 2011; in 69 cases a colonoscopic evaluation was recommended for incidental FDG-avid lesions. RESULTS: Of these 69 cases, 51 underwent colonoscopy because of the potential need for further treatment. The maximum standardized uptake values (SUVmax) ranged from 5.0 to 42.0 with an average of 10.9. In 44 of the 51 patients, a histopathological abnormality was found on colonoscopy, 44 in the location described by PET/CT. A further 38 lesions were identified that were not visible on PET/CT. The histopathological evaluation in the 51 patients revealed 14 hyperplastic polyps, 27 adenomas with low-grade and 4 with high-grade dysplasia, 3 adenocarcinomas and 1 neuro-endocrine tumour. CONCLUSION: Incidental findings of focal colorectal FDG uptake should lead to further workup with colonoscopy. The SUVmax was not predictive for higher grade histologies. With an SUV of 5 the yield was high for colonic premalignant and malignant lesions. However, malignancy cannot be ruled out in focal lesions with an SUV of less than 5, and for individual patients a colonoscopy should not be ruled out.
BACKGROUND: MicroRNAs have been reported to play roles as oncogenes or tumor suppressor genes in human cancers. However, the expression levels of miR-145 in oral squamous cell carcinoma (OSCC) are unclear. The purpose of...BACKGROUND: MicroRNAs have been reported to play roles as oncogenes or tumor suppressor genes in human cancers. However, the expression levels of miR-145 in oral squamous cell carcinoma (OSCC) are unclear. The purpose of this study was to investigate the status of miR-145 expression in OSCC and determine its clinical significance. PATIENTS AND METHODS: We examined miR-145 levels in 62 OSCC tissue samples and cell lines by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The relationship between miR-145 expression and clinicopathologic factors of OSCC patients was analyzed. RESULTS: The proportion of miR-145 low expression was 82.26% (51/62) among the 62 OSCC patients, and expression levels of miR-145 in OSCC tissue samples and cell lines were significantly lower than in non-tumor controls. miR-145 expression levels were not significantly associated with age (p = 0.607), sex (p = 0.213), location (p = 0.952), histology (p = 0.603), pT stage (p = 0.305), pTNM stage (p = 0.471), and lymphatic metastasis (p = 1.000). CONCLUSION: miR-145 may be involved in the early tumorigenesis of oral squamous cells, and might be a potential biomarker in the early diagnosis of OSCC.
BACKGROUND: Exposure to radiation resulting from diagnostic imaging procedures probably increases late cancer risk. Patterns of care regarding the application of computed tomography (CT) imaging in testicular cancer pati...BACKGROUND: Exposure to radiation resulting from diagnostic imaging procedures probably increases late cancer risk. Patterns of care regarding the application of computed tomography (CT) imaging in testicular cancer patients were investigated. METHODS: The database of a large German health insurance company comprising 850,000 insured men was searched for cases of testicular cancer arising in the years 2005 and 2006. The number of CT scans applied during a 3-year period of follow-up was noted for each individual patient and the resulting cumulative radiation dose was estimated. The number of CT scans actually observed was compared to guideline recommendations. RESULTS: 177 patients were identified. Within the 3-year observation period, patients received a mean of 4.4 CT scans (standard error: 0.4) whereas a number of 6.2 would have been expected according to contemporary guidelines. Patients were exposed to an estimated total median diagnostic radiation dose of 30 millisieverts (mSv) (interquartile range: 10-54 mSv). CONCLUSION: There is a considerable gap between recommendation and actual performance regarding the number of CT scans applied to testicular cancer patients. Unfamiliarity of clinicians with guidelines as well as poor acceptance of high numbers of CT scans scheduled may have contributed to create this particular pattern of care.
BACKGROUND: Prostaglandin endoperoxide synthase 2 (PTGS2) is involved in prostate cancer (PCa) by stimulating cell proliferation, promoting angiogenesis, inhibiting apoptosis, and mediating immune suppression. 8473T>C, l...BACKGROUND: Prostaglandin endoperoxide synthase 2 (PTGS2) is involved in prostate cancer (PCa) by stimulating cell proliferation, promoting angiogenesis, inhibiting apoptosis, and mediating immune suppression. 8473T>C, located in the 3' UTR of the PTGS2 gene, has been considered to influence PCa risk. METHODS: We searched Medline, PubMed, Elsevier, and Web of Science (updated to February 5, 2012) using the following search terms: '8473T>C' or 'rs5275', 'genetic variant' or 'polymorphism', 'prostate cancer', 'cancer', 'PTGS2' or 'COX-2'. Odds ratios with 95% confidence intervals were assessed by using fixed or random effect models. Both funnel plot and Egger's test were used to assess the publication bias. RESULTS: Finally, 5 case control studies were included. Overall, no evidence was observed of a relationship between the 8473T>C and PCa risk in any genetic model. No significant association was found in the studies whose controls conform to the Hardy-Weinberg equilibrium. In the stratified analysis, significant association was detected in other populations (except for Caucasians), which were based on hospitals. CONCLUSION: The 8473T>C polymorphism may have little association with PCa risk among Caucasians, but might be involved in PCa risk in other ethnicities. Nevertheless, more well-designed studies with a larger sample size including different ethnicities should be conducted.
AIM: The aim of the current study was to evaluate whether early detection of brain metastases (BMs) could improve survival outcomes in human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients. MATE...AIM: The aim of the current study was to evaluate whether early detection of brain metastases (BMs) could improve survival outcomes in human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients. MATERIAL AND METHODS: HER2-positive breast cancer patients without BMs who had no neurological symptoms within 12 months from diagnosis or relapse time of the disease were included in the study. The patients were distributed into 2 groups: Group 1 comprised patients without metastases; group 2 comprised patients with metastases. The symptomatic historic control group with BMs was defined retrospectively for survival comparisons. RESULTS: 55 (57.3%) and 41 (42.7%) patients were in groups 1 and 2, respectively. 11 of the 96 patients (11.5%) had occult BMs, and 9 of them were in group 2 whereas only 2 patients were in group 1 (22% vs. 3.6%, respectively; p = 0.008). While the median survival times from the first metastasis (28.7 vs. 22.5 months, respectively; p = 0.561) and BM (6.8 vs. 6.1 months, respectively; p = 0.511) were similar, cerebral death was numerically different (16.7% vs. 46.3%; p = 0.221) between asymptomatic (n = 9) and symptomatic patients (n = 53). CONCLUSIONS: BMs were detected very rarely in asymptomatic, non-metastatic HER2-positive breast cancer patients compared with asymptomatic, metastatic patients. Furthermore, although early detection of BMs decreases the cerebral death rate, it does not prolong the survival rate in metastatic patients.