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Buxtehude, Germany

Trefzer U.,Dermatologikum Berlin | Gutzmer R.,Klinik fur Dermatologie | Wilhelm T.,Charite - Medical University of Berlin | Schenck F.,Hautarzte Zentrum Hanover | And 5 more authors.
Journal for ImmunoTherapy of Cancer

Background: Aviscumine, a recombinant plant protein, is an immune modulator that induces ribotoxic stress at the 28S ribosomal RNA subunit. In this way cytokine release and T-cell responses are enhanced. This phase II trial was conducted to test the efficacy and safety of aviscumine in patients with systemically pre-treated metastatic melanoma stage IV.Methods: A total of 32 patients with progressive stage IV melanoma after failure of standard therapy were enrolled onto a single-arm, multi-centre, open-label, phase II trial. All patients had an ECOG performance status of 0 or 1. Patients received 350 ng aviscumine twice weekly by subcutaneous injection until progression. The primary end points were progression-free survival (PFS) and overall survival (OS). Safety was assessed as adverse events (AEs). Tumor response was assessed every eight weeks and survival of patients was followed up to one year after the end of therapy. Thirty one patients (intent-to-treat population (ITT)) were assessed for efficacy; safety was assessed in the whole population.Results: One patient achieved a partial response (PR) and 10 patients showed stable disease/no change (SD). The median progression-free survival (mPFS) was 63 days (95% CI 57-85) and median overall survival (mOS) was 335 days (95% CI 210-604). In total 210 treatment-emergent adverse events were recorded. Grade 1 or 2 AEs occurred in 72% of patients and were mostly application-site effects such as pruritus Grade 3-4 treatment-emergent drug-related adverse events occurred in 9% of patients.Conclusion: These results suggest that aviscumine may have a clinical impact in patients with previously treated metastatic melanoma and provide rationale for further clinical evaluation of this agent. In the light of effective new immune checkpoint blockers it might be a candidate for combinations with these agents.Trial registration: ClinicalTrials.gov: NCT00658437. © 2014 Lentzen et al.; licensee BioMed Central. Source

Malvehy J.,University of Barcelona | Hauschild A.,University of Kiel | Curiel-Lewandrowski C.,Arizona Cancer Center | Mohr P.,Elbe Klinikum Buxtehude | And 17 more authors.
British Journal of Dermatology

Summary Background Even though progress has been made, the detection of melanoma still poses a challenge. In light of this situation, the Nevisense electrical impedance spectroscopy (EIS) system (SciBase AB, Stockholm, Sweden) was designed and shown to have the potential to be used as an adjunct diagnostic tool for melanoma detection.Objectives To assess the effectiveness and safety of the Nevisense system in the distinction of benign lesions of the skin from melanoma with electrical impedance spectroscopy.Methods This multicentre, prospective, and blinded clinical study was conducted at five American and 17 European investigational sites. All eligible skin lesions in the study were examined with the EIS-based Nevisense system, photographed, removed by excisional biopsy and subjected to histopathological evaluation. A postprocedure clinical follow-up was conducted at 7 ± 3 days from the initial measurement. A total of 1951 patients with 2416 lesions were enrolled into the study; 1943 lesions were eligible and evaluable for the primary efficacy end point, including 265 melanomas - 112 in situ and 153 invasive melanomas with a median Breslow thickness of 0·57 mm [48 basal cell carcinomas (BCCs) and seven squamous cell carcinomas (SCCs)].Results The observed sensitivity of Nevisense was 96·6% (256 of 265 melanomas) with an exact one-sided 95% lower confidence bound estimated at 94·2% and an observed specificity of 34·4%, and an exact two-sided 95% confidence bound estimated at 32·0-36·9%. The positive and negative predictive values of Nevisense were 21·1% and 98·2%, respectively. The observed sensitivity for nonmelanoma skin cancer was 100% (55 of 48 BCCs and seven SCCs) with an exact two-sided 95% confidence bound estimated at 93·5-100·0%.Conclusions Nevisense is an accurate and safe device to support clinicians in the detection of cutaneous melanoma. What's already known about this topic? Although progress has been made in the detection of melanoma it still poses a challenge. Electrical impedance spectroscopy (EIS) may potentially be used as a diagnostic aid for the detection of melanoma. What does this study add? In the largest international prospective study of its kind in melanoma detection, the EIS system Nevisense was shown to be both accurate and safe in the lesion cohort studied. In the absence of a perfect gold standard, the accuracy of a device should be compared with the consensus diagnosis from multiple experts. © 2014 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists. © 2014 British Association of Dermatologists. Source

Hofmann M.A.,Charite - Medical University of Berlin | Hauschild A.,University of Kiel | Mohr P.,Elbe Klinikum Buxtehude | Garbe C.,University of Tubingen | And 7 more authors.
Melanoma Research

This prospective, nonrandomized multicentre, phase III study compared best supportive care (BSC) alone with cisplatin, vindesine and dacabazine-based (CVD) chemotherapy and BSC in patients with advanced melanoma. A total of 117 pretreated patients with metastatic melanoma were evaluated, 34 patients in arm A (BSC) and 83 in arm B (BSC and CVD). Primary endpoint was overall survival and secondary endpoints were disease control rate and quality of life (European Organisation for Research and Treatment of Cancer QLQ-C30). Owing to sparse recruitment of patients for randomization, the protocol has been changed based on patients' choice. Baseline characteristics were imbalanced with respect to the Karnofsky Performance Index (P=0.001), the existence of brain metastases (P=0.035) and earlier application of chemoimmunotherapy (P=0.038). Disease control was observed in 8.8% of patients in arm A and in 28.9% of patients in arm B (P=0.028). Median overall survival time was 137 days in arm A and 229 days in arm B (P=0.014). Multivariate analyses could not ascribe this prognostic benefit to CVD treatment. No significant difference in the quality of life could be found. This study could not detect clear survival benefits for polychemotherapy with CVD compared with BSC alone in patients with advanced metastatic melanoma. Interestingly, having the choice of chemotherapy or BSC alone in a second-line situation, more than 70% of patients chose polychemotherapy. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source

Nashan D.,Albert Ludwigs University of Freiburg | Reuter K.,Albert Ludwigs University of Freiburg | Mohr P.,Elbe Klinikum Buxtehude | Agarwala S.S.,Temple University
Melanoma Research

Fatigue is the most common toxicity associated with adjuvant interferon-α treatment of melanoma, with an incidence ranging from 80 to 90%. It may be dose-limiting and may lead to treatment discontinuation in a large proportion of patients. Fatigue is commonly diagnosed by self-report, does not have a precise definition, and has a high degree of overlap with symptoms of depression. Specific fatigue scales have been developed over the past few years, assessing fatigue either one-dimensionally or multi-dimensionally. However, the characteristics that define an accurate and efficient fatigue scale have not been established. Despite the debilitating effects of fatigue resulting from interferon treatment, a large proportion of patients place a higher value on the relapse-free survival benefits of treatment compared with quality-of-life deterioration. Pharmacologic interventions to treat and manage fatigue are not well established, although psychostimulants are sometimes used. We recommend incorporating structure and routine into day-to-day activities to cope with fatigue. In our experience, participating in moderate physical activities and drinking sufficient fluids are key factors to ensuring efficient fatigue management. A multidisciplinary team is necessary to translate the fatigue management recommendations into practice. Clinical trials using appropriate fatigue assessment tools to investigate interventional therapies are warranted. We recommend the use of the cross-culturally European Organisation for Research and Treatment of Cancer quality-of-life questionnaire Fatigue Module FA13 for clinical trials as well as in day-to-day clinical trials. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source

Aberg P.,Karolinska Institutet | Birgersson U.,Karolinska Institutet | Birgersson U.,SciBase AB | Elsner P.,Friedrich - Schiller University of Jena | And 2 more authors.
Experimental Dermatology

Background: The accuracy of diagnosis of skin cancer and especially of early malignant melanoma is most important to reduce its morbidity and mortality. Previous pilot studies using electrical impedance measurements indicate statistically significant accuracies for the detection of skin cancer. Objectives: The aim of this study is to investigate the accuracy of electrical impedance spectra to distinguish between malignant melanoma and benign skin lesions using an automated classification algorithm. Patients/Methods: Electrical impedance spectra were measured in a multi-centre study at 12 clinics around Europe. Data from 285 histologically analysed lesions were used to train an algorithm to sort out lesions for automatic detection of melanoma. Another data cohort of 210 blinded lesions (148 various benign lesions and 62 malignant melanomas where 38 being from Breslow thickness ≤1mm) from 183 patients was thereafter used to estimate the accuracy of the technique. Results: Observed sensitivity to malignant melanoma is 95% (59/62) and observed specificity 49% (72/148). Conclusions: The results suggest that electrical impedance spectra can distinguish between malignant melanoma and benign skin lesions. Although it is indicated that the accuracy of the device is clinically promising, the overall performance, and the sensitivity to thin malignant melanomas, must be improved and thoroughly validated before the instrument can be used as a routine stand-alone diagnostic decision support tool. The technique is under revision to further improve the reproducibility, specificity and sensitivity. © 2011 John Wiley & Sons A/S. Source

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