Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 103
Filter
1.
Endocr Relat Cancer ; 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38913539

ABSTRACT

Prospective data are lacking on early somatostatin analog (SSA) therapy in bronchopulmonary neuroendocrine tumors (BP-NETs; typical and atypical carcinoids [TCs and ACs]). SPINET (EudraCT: 2015-004992-62; NCT02683941) was a phase III, double-blind study of lanreotide autogel/depot (LAN; 120 mg every 28 days) plus best supportive care (BSC) versus placebo plus BSC, with an optional open label treatment phase (LAN plus BSC). Patients had metastatic/unresectable, somatostatin receptor (SSTR)-positive TCs or ACs. Recruitment was stopped early owing to slow accrual; eligible patients from the double-blind phase transitioned to open-label LAN. The adapted primary endpoint was progression free survival (PFS) during either phase for patients receiving LAN. Seventy-seven patients were randomized (LAN, n=51 [TCs, n=29; ACs, n=22]; placebo, n=26 [TCs, n=16; ACs, n=10). Median (95% confidence interval [CI]) PFS during double-blind and OL phases in patients receiving LAN was 16.6 (11.3; 21.9) months overall (primary endpoint), 21.9 (12.8, not calculable [NC]) months in TCs and 13.8 (5.4; 16.6) months in ACs. During double-blind treatment, median (95% CI) PFS was 16.6 (11.3; 21.9) months for LAN versus 13.6 (8.3; NC) months for placebo (not significant); corresponding values were 21.9 (13.8; NC) and 13.9 (13.4; NC) months, respectively, in TCs and 13.8 (5.4; 16.6) and 11.0 (2.8; 16.9) months, respectively, in ACs. Patients' quality of life did not deteriorate and LAN was well tolerated. Although recruitment stopped early and the predefined sample size was not met, SPINET is the largest prospective study to date of SSA therapy in SSTR positive TCs and ACs and suggests clinical benefit in TCs.

2.
ESMO Open ; 9(2): 102237, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38350336

ABSTRACT

BACKGROUND: In 2019, we reported the first efficacy and safety analysis of EUCROSS, a phase II trial investigating crizotinib in ROS1 fusion-positive lung cancer. At that time, overall survival (OS) was immature and the effect of crizotinib on intracranial disease control remained unclear. Here, we present the final analysis of OS, systemic and intracranial activity, and the impact of co-occurring aberrations. MATERIALS AND METHODS: EUCROSS was a prospective, single-arm, phase II trial. The primary endpoint was best overall response rate (ORR) using RECIST 1.1. Secondary and exploratory endpoints were progression-free survival (PFS), OS, and efficacy in pre-defined subgroups. RESULTS: Median OS of the intention-to-treat population (N = 34) was 54.8 months [95% confidence interval (CI) 20.3 months-not reached (NR); median follow-up 81.4 months] and median all-cause PFS of the response-evaluable population (N = 30) was 19.4 months (95% CI 10.1-32.2 months). Time on treatment was significantly correlated with OS (R = 0.82; P < 0.0001). Patients with co-occurring TP53 aberrations (28%) had a significantly shorter OS [hazard ratio (HR) 11; 95% CI 2.0-56.0; P = 0.006] and all-cause PFS (HR 4.2; 95% CI 1.2-15; P = 0.025). Patients with central nervous system (CNS) involvement at baseline (N = 6; 20%) had a numerically shorter median OS and all-cause PFS. Median intracranial PFS was 32.2 months (95% CI 23.7 months-NR) and the rate of isolated CNS progression was 24%. CONCLUSIONS: Our final analysis proves the efficacy of crizotinib in ROS1-positive lung cancer, but also highlights the devastating impact of TP53 mutations on survival and treatment efficacy. Additionally, our data show that CNS disease control is durable and the risk of CNS progression while on crizotinib treatment is low.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Crizotinib/pharmacology , Crizotinib/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Protein-Tyrosine Kinases/genetics , Prospective Studies , Proto-Oncogene Proteins/genetics , Central Nervous System
3.
Naturwissenschaften ; 110(5): 42, 2023 Aug 16.
Article in English | MEDLINE | ID: mdl-37584870

ABSTRACT

We describe two large predators from the hominoid-bearing Khorat sand pits, Nakhon Ratchasima Province, northeastern Thailand: a new genus of pantherine, Pachypanthera n. gen., represented by partial mandible and maxilla and an indeterminate sabre-toothed cat, represented by a fragment of upper canine. The morphological characters of Pachypanthera n. gen., notably the large and powerful canine, the great robustness of the mandibular body, the very deep fossa for the m. masseter, the zigzag HSB enamel pattern, indicate bone-cracking capacities. The genus is unique among Felidae as it has one of the most powerful and robust mandibles ever found. Moreover, it may be the oldest known pantherine, as other Asian pantherines are dated back to the early Pliocene. The taxa we report here are the only carnivorans known from the late Miocene of Thailand. Although the material is rather scarce, it brings new insights to the evolutionary history of Neogene mammals of Southeast Asia, in a geographic place which is partly "terra incognita."


Subject(s)
Carnivora , Felidae , Hominidae , Animals , Felidae/anatomy & histology , Fossils , Muscimol , Sand , Thailand
4.
ESMO Open ; 7(5): 100572, 2022 10.
Article in English | MEDLINE | ID: mdl-36108559

ABSTRACT

BACKGROUND: Rates of disease recurrence and death following surgery remain high in early-stage non-small-cell lung cancer (NSCLC), despite adjuvant treatment and curative intent. Recently, osimertinib showed overwhelming evidence for disease-free survival (DFS), as demonstrated by an overall reduction in the risk of disease recurrence or death in the adjuvant setting of 80% versus control in the ADAURA study (stage IB-IIIA; hazard ratio 0.20; 99.12% confidence interval 0.14-0.30; P < 0.001). However, due to the early unblinding of ADAURA and lack of mature overall survival data, there is a need to qualitatively confirm consensus on the clinical and patient relevance of DFS. MATERIALS AND METHODS: We conducted a modified Delphi panel study consisting of two rounds of surveys, followed by a consensus meeting. An international panel of experts in the field of NSCLC and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) (n = 13) was asked to rate agreement and comment on a list of pre-defined statements covering key consensus gaps. Statements were eliminated or updated between surveys, depending on the level of agreement. A final list of agreed-upon statements was drafted in the consensus meeting. RESULTS: Consensus was reached on 32 qualitative statements, with topics including unmet needs in early-stage NSCLC, the value of DFS, and the value of osimertinib. Crucially, DFS was agreed to be a clinically and patient-relevant endpoint in adjuvant NSCLC. The relevance of DFS was found to relate to the ability of an adjuvant therapy, such as osimertinib, to keep patients in the clinically valuable curative intent setting, while preventing the burden associated with distant and locoregional recurrence, and progressive disease. CONCLUSIONS: Addressing the need for measures that reflect clinical benefit is essential to continue improving outcomes for NSCLC patients. To that end, this work provides a qualitative framework for clinicians to consider the clinical and patient relevance of DFS in adjuvant NSCLC and the benefit demonstrated in ADAURA thus far.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Disease-Free Survival , ErbB Receptors , Lung Neoplasms/drug therapy , Consensus , Delphi Technique , Chemotherapy, Adjuvant , Mutation , Neoplasm Recurrence, Local/chemically induced , Neoplasm Recurrence, Local/drug therapy , Protein Kinase Inhibitors/therapeutic use
5.
Clin Oncol (R Coll Radiol) ; 34(7): 459-468, 2022 07.
Article in English | MEDLINE | ID: mdl-35012901

ABSTRACT

AIMS: To evaluate the efficacy and safety of nintedanib plus docetaxel in patients with advanced adenocarcinoma non-small cell lung cancer (NSCLC) who progressed after chemotherapy and immune checkpoint inhibitor (ICI) therapy. MATERIALS AND METHODS: VARGADO (NCT02392455) is an ongoing, prospective, non-interventional, real-world study of nintedanib plus docetaxel after first-line chemotherapy in the routine clinical treatment of patients with locally advanced, metastatic or locally recurrent adenocarcinoma NSCLC. Data were collected during routine visits. We report the results from cohort B (n = 80), who received third-line nintedanib plus docetaxel after first-line chemotherapy and second-line ICI therapy. RESULTS: The median duration of follow-up was 12.4 months. Median progression-free survival from initiation of third-line nintedanib plus docetaxel was 6.4 months (95% confidence interval 4.8, 7.3); median overall survival was 12.1 months (95% confidence interval 9.4, 13.5). The 1-year overall survival rate after initiation of third-line nintedanib plus docetaxel treatment (primary end point) was 52% (95% confidence interval 38.0%, 64.4%). Among 64 patients with a documented response, the objective response rate was 50% (n = 32; one complete response and 31 partial responses) and the disease control rate was 86% (n = 55). There were no new safety signals or unexpected toxicities. Among all treated patients, 74% (n = 59) experienced drug-related adverse events, most commonly (nintedanib-related/docetaxel-related) diarrhoea (34%/24%), a decreased white blood cell count (11%/19%) and nausea (13%/16%). CONCLUSIONS: Nintedanib plus docetaxel demonstrated a high response rate and disease stabilisation in the third-line setting after failure of prior chemotherapy and ICI treatment, with a manageable safety profile. These results suggest that nintedanib plus docetaxel represents an efficient treatment option after failure of prior ICIs. The ongoing VARGADO study provides valuable real-world data to inform clinical decision-making regarding treatment sequencing after chemotherapy and ICI failure in patients with adenocarcinoma NSCLC.


Subject(s)
Adenocarcinoma , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Adenocarcinoma/pathology , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Non-Small-Cell Lung/pathology , Docetaxel , Humans , Immune Checkpoint Inhibitors , Indoles , Lung Neoplasms/pathology , Neoplasm Recurrence, Local/drug therapy , Prospective Studies , Treatment Outcome
7.
Ann Oncol ; 33(1): 57-66, 2022 01.
Article in English | MEDLINE | ID: mdl-34624497

ABSTRACT

BACKGROUND: Several strategies have been investigated to improve the 4% survival advantage of adjuvant chemotherapy in early-stage non-small-cell lung cancer (NSCLC). In this investigator-initiated study we aimed to evaluate the predictive utility of the messenger RNA (mRNA) expression levels of excision repair cross complementation group 1 (ERCC1) and thymidylate synthase (TS) as assessed in resected tumor. PATIENTS AND METHODS: Seven hundred and seventy-three completely resected stage II-III NSCLC patients were enrolled and randomly assigned in each of the four genomic subgroups to investigator's choice of platinum-based chemotherapy (C, n = 389) or tailored chemotherapy (T, n = 384). All anticancer drugs were administered according to standard doses and schedules. Stratification factors included stage and smoking status. The primary endpoint of the study was overall survival (OS). RESULTS: Six hundred and ninety patients were included in the primary analysis. At a median follow-up of 45.9 months, 85 (24.6%) and 70 (20.3%) patients died in arms C and T, respectively. Five-year survival for patients in arms C and T was of 65.4% (95% CI (confidence interval): 58.5% to 71.4%) and 72.9% (95% CI: 66.5% to 78.3%), respectively. The estimated hazard ratio (HR) was 0.77 (95% CI: 0.56-1.06, P value: 0.109) for arm T versus arm C. HR for recurrence-free survival was 0.89 (95% CI: 0.69-1.14, P value: 0.341) for arm T versus arm C. Grade 3-5 toxicities were more frequently reported in arm C than in arm T. CONCLUSION: In completely resected stage II-III NSCLC tailoring adjuvant chemotherapy conferred a non-statistically significant trend for OS favoring the T arm. In terms of safety, the T arm was associated with better efficacy/toxicity ratio related to the different therapeutic choices in the experimental arm.


Subject(s)
Antineoplastic Agents , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/surgery , Chemotherapy, Adjuvant , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/surgery , Neoplasm Staging , Pharmacogenetics
8.
Pneumologie ; 75(4): 276-283, 2021 Apr.
Article in German | MEDLINE | ID: mdl-33461225

ABSTRACT

AIM: Retrospective analysis of data from PneuNET registry to evaluate clinical follow up of patients with typical and atypical bronchopulmonary carcinoid (bpNET). METHOD: Three lung cancer centres in Berlin included patients in the registry between 2007 and 2016. Inclusion criteria were: diagnosis of typical or atypical carcinoid, age > 18 years, follow-up for not less than 2 years. Frequency, gender, functional status, smoking status, localisation of the tumour, biomarker, diagnostic and therapeutic procedures and follow-up were evaluated. RESULTS: Since 01. 01. 2007, 187 patients with bronchopulmonary carcinoid had been included in the registry. The ratio between TC and AC was 8:2. The median age was 65.4 years and 64 % of patients were women. 10.7 % of patients had pulmonary symptoms, 2 patients a carcinoid syndrome, no patient was detected with MEN-1-syndrome. 87.7 % of patients had undergone surgery, 69.5 % as lobectomy with systematic lymphadenectomy. Only 10 % of patients were diagnosed with Stage IV disease, with atypical carcinoid predominating Systemic therapies included chemotherapy, everolimus and somatostatin analogues. CONCLUSION: Bronchopulmonary carcinoids are well differentiated tumours of the lung. The early stage diagnosis offers the possibility of local therapy with excellent prognosis. We have improved systemic treatment options with mTOR-inhibitor everolimus and somatostatin analogues also in advanced stage of the disease. Because of the rareness of this heterogenous group of tumours, it is meaningful to collect data systematically in order to have a standardised algorithm of diagnostic procedures and therapy assessment.


Subject(s)
Carcinoid Tumor , Lung Neoplasms , Adult , Aged , Berlin , Carcinoid Tumor/diagnosis , Carcinoid Tumor/therapy , Female , Humans , Lung Neoplasms/diagnosis , Lung Neoplasms/epidemiology , Lung Neoplasms/therapy , Middle Aged , Prognosis , Retrospective Studies
9.
Pneumologie ; 74(6): 358-365, 2020 Jun.
Article in German | MEDLINE | ID: mdl-32294763

ABSTRACT

The enormous increase in patients with severe respiratory distress due to the COVID-19 pandemic outbreak requires a systematic approach to optimize ventilated patient at risk flow. A standardised algorithm called "SAVE" was developed to distribute patients with COVID-19 respiratory distress syndrome requiring invasive ventilation. This program is established by now in Berlin. An instrumental bottleneck of this approach is the vacant slot assignment in the intensive care unit to guarantee constant patient flow. The transfer of the patients after acute care treatment is needed urgently to facilitate the weaning process. In a next step we developed a triage algorithm to identify patients at SAVE intensive care units with potential to wean and transfer to weaning institutions - we called POST SAVE. This manuscript highlights the algorithms including the use of a standardised digital evaluation tool, the use of trained navigators to facilitate the communication between SAVE intensive care units and weaning institutions and the establishment of a prospective data registry for patient assignment and reevaluation of the weaning potential in the future.


Subject(s)
Intensive Care Units/organization & administration , Practice Guidelines as Topic , Ventilator Weaning , Berlin , Betacoronavirus , COVID-19 , Coronavirus , Coronavirus Infections/epidemiology , Coronavirus Infections/therapy , Disease Outbreaks/prevention & control , Humans , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/therapy , Prospective Studies , SARS-CoV-2
10.
Pneumologie ; 74(1): 24-34, 2020 Jan.
Article in German | MEDLINE | ID: mdl-31863422

ABSTRACT

Sarcoidosis is a multisystemic granulomatous disorder which affects the respiratory system in the majority of the cases. Symptomatic cardiac manifestations are found in less than 10 % of the affected cohorts and show a large heterogeneity based on the ethnic background. Cardiac sarcoidosis is not only found in patients with rhythmogenic heart disease, such as atrial and ventricular fibrillation but also in all phenotypes of cardiomyopathy. The overall morbidity and mortality caused by cardiac sarcoidosis in Germany remains unclear and large prospective international observational studies.underline the importance of this disease entity. This consensus paper on diagnostic and therapeutic algorithms for cardiac sarcoidosis is based on a current literature search and forms an expert opinion statement under the auspices of the German Respiratory Society and the German Cardiac Society. The rationale of this statement is to provide algorithms to facilitate clinical decision-making based on the individual case situation.


Subject(s)
Cardiology/standards , Practice Guidelines as Topic , Sarcoidosis, Pulmonary/diagnosis , Sarcoidosis, Pulmonary/therapy , Cardiomyopathies , Consensus , Germany/epidemiology , Humans , Interdisciplinary Communication , Pulmonary Medicine/standards , Societies, Medical
11.
Pneumologie ; 73(4): 225-232, 2019 Apr.
Article in German | MEDLINE | ID: mdl-30895591

ABSTRACT

There is a paucity of data about the at home monitoring and the outpatient setting and care of patients with non-invasive ventilation. We here show, in a prospective study, that both standardized outpatient care visits as well as quality of life monitoring at home are safe and feasible. Monitoring and managing the quality of care at home did not lead to an increase of non-elective hospitalisations or deterioration of respiratory disease burden.


Subject(s)
Ambulatory Care , Home Care Services , Noninvasive Ventilation/statistics & numerical data , Respiration, Artificial , Respiratory Insufficiency/therapy , Humans , Prospective Studies , Quality of Health Care , Quality of Life
12.
Ann Oncol ; 29(10): 2068-2075, 2018 10 01.
Article in English | MEDLINE | ID: mdl-30165392

ABSTRACT

Background: We analyzed whether co-occurring mutations influence the outcome of systemic therapy in ALK-rearranged non-small-cell lung cancer (NSCLC). Patients and methods: ALK-rearranged stage IIIB/IV NSCLC patients were analyzed with next-generation sequencing and fluorescence in situ hybridization analyses on a centralized diagnostic platform. Median progression-free survival (PFS) and overall survival (OS) were determined in the total cohort and in treatment-related sub-cohorts. Cox regression analyses were carried out to exclude confounders. Results: Among 216 patients with ALK-rearranged NSCLC, the frequency of pathogenic TP53 mutations was 23.8%, while other co-occurring mutations were rare events. In ALK/TP53 co-mutated patients, median PFS and OS were significantly lower compared with TP53 wildtype patients [PFS 3.9 months (95% CI: 2.4-5.6) versus 10.3 months (95% CI: 8.6-12.0), P < 0.001; OS 15.0 months (95% CI: 5.0-24.9) versus 50.0 months (95% CI: 22.9-77.1), P = 0.002]. This difference was confirmed in all treatment-related subgroups including chemotherapy only [PFS first-line chemotherapy 2.6 months (95% CI: 1.3-4.1) versus 6.2 months (95% CI: 1.8-10.5), P = 0.021; OS 2.0 months (95% CI: 0.0-4.6) versus 9.0 months (95% CI: 6.1-11.9), P = 0.035], crizotinib plus chemotherapy [PFS crizotinib 5.0 months (95% CI: 2.9-7.2) versus 14.0 months (95% CI: 8.0-20.1), P < 0.001; OS 17.0 months (95% CI: 6.7-27.3) versus not reached, P = 0.049] and crizotinib followed by next-generation ALK-inhibitor [PFS next-generation inhibitor 5.4 months (95% CI: 0.1-10.7) versus 9.9 months (95% CI: 6.4-13.5), P = 0.039; OS 7.0 months versus 50.0 months (95% CI: not reached), P = 0.001). Conclusions: In ALK-rearranged NSCLC co-occurring TP53 mutations predict an unfavorable outcome of systemic therapy. Our observations encourage future research to understand the underlying molecular mechanisms and to improve treatment outcome of the ALK/TP53 co-mutated subgroup.


Subject(s)
Anaplastic Lymphoma Kinase/genetics , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/mortality , Gene Rearrangement , Lung Neoplasms/mortality , Mutation , Tumor Suppressor Protein p53/genetics , Adenocarcinoma/drug therapy , Adenocarcinoma/genetics , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Carcinoma, Adenosquamous/drug therapy , Carcinoma, Adenosquamous/genetics , Carcinoma, Adenosquamous/mortality , Carcinoma, Adenosquamous/pathology , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Cohort Studies , Female , Follow-Up Studies , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Male , Middle Aged , Prognosis , Survival Rate , Young Adult
13.
Pneumologie ; 72(8): 590-597, 2018 Aug.
Article in German | MEDLINE | ID: mdl-30089330

ABSTRACT

BACKGROUND: Augmentation with human alpha-1 proteinase inhibitor is the only specific treatment for Alpha-1-Antitrypsin Deficiency (AATD), a rare genetic disease with symptoms of progressive COPD. OBJECTIVES: A prospective long-term exploration of outcomes during the "Alpha-1-Mobile" home care AAT augmentation program in seven advanced-stage patients. METHODS: Patients received weekly i. v. AAT augmentation and COPD therapy. Symptoms, lung function, health status, quality-of-life aspects, and safety were documented continuously. Outcomes during six years of home care augmentation therapy were observed and evaluated on an inter- and intraindividual basis. FEV1 profiles were compared to pre-program data. RESULTS: The seven patients had a mean age of 56.7 (40-68) years and had previously received augmentation for 8.8 (1-19) years. Compared to the three-year preprogram period, functional decline of FEV1 (ΔFEV1 0.47 L vs 0.17 L) slowed. Mean QoL scores showed seasonal fluctuations in the first three years of observation, and then stabilized. All blood samples tested exceeded the protective threshold of 50 mg/dL with a dose of 60 mg AAT/kg/week. Less than one exacerbation-related hospitalization occurred per patient-year. No adverse events of related to augmentation therapy were observed. CONCLUSIONS: Home care with i. v. augmentation therapy by medical professionals contributes to optimum care through consistent treatment and close health-status monitoring in our collective. Exacerbation-related hospitalizations were largely avoided. "Alpha-1-Mobile" was well accepted, practical, and safe.


Subject(s)
Home Care Services , Lung/physiopathology , Pulmonary Emphysema/drug therapy , alpha 1-Antitrypsin Deficiency/drug therapy , alpha 1-Antitrypsin/administration & dosage , Aged , Health Status , Humans , Middle Aged , Program Evaluation , Prospective Studies , Pulmonary Emphysema/genetics , Pulmonary Emphysema/psychology , Quality of Life , alpha 1-Antitrypsin Deficiency/genetics , alpha 1-Antitrypsin Deficiency/psychology
14.
Ann Oncol ; 28(8): 1898-1902, 2017 Aug 01.
Article in English | MEDLINE | ID: mdl-28535181

ABSTRACT

BACKGROUND: Large-cell neuroendocrine carcinoma of the lung (LCNEC) is a rare disease with poor prognosis and limited treatment options. Neuroendocrine tumors frequently show overactivation of the mTOR pathway. Based on the good activity of the mTOR inhibitor everolimus in different types of neuroendocrine tumors and the results of a previous phase I trial, we evaluated the efficacy and safety of everolimus in combination with carboplatin and paclitaxel as upfront treatment for patients with advanced LCNEC. PATIENTS AND METHODS: In this prospective, multicenter phase II trial chemotherapy-naive patients with stage IV LCNEC received 5 mg everolimus daily combined with paclitaxel 175 mg/m2 and carboplatin AUC 5 every 3 weeks for a maximum of four cycles followed by maintenance everolimus 5 mg daily until progression. Efficacy parameters were determined based on central radiologic assessment. RESULTS: Forty-nine patients with a mean age of 62 ±9 years and a predominance of male (71%) smokers (98%) were enrolled in 10 German centers. The overall response rate was 45% (95% confidence interval [CI] 31%-60%), the disease control rate 74% (CI 59%-85%), the median progression-free survival 4.4 (CI 3.2-6) months and the median overall survival 9.9 (CI 6.9-11.7) months. The progression-free survival rate at 3 months (primary end point) was 76% (CI 64%-88%) according to Kaplan-Meier. Grade-3/4 toxicities occurred in 51% of patients and mainly consisted of general physical health deterioration (8%), cytopenias (24%), infections (10%) and gastrointestinal problems (8%). Typical everolimus-related adverse events, like stomatitis, rash and ocular problems occurred only in a minority of patients (<15%) and were exclusively of grade 1-2. CONCLUSION: Everolimus in combination with carboplatin and paclitaxel is an effective and well-tolerated first-line treatment for patients with metastatic LCNEC. REGISTERED CLINICAL TRIAL NUMBERS: EudraCT number 2010-022273-34, NCT01317615.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Large Cell/drug therapy , Carcinoma, Neuroendocrine/drug therapy , Lung Neoplasms/drug therapy , Adult , Aged , Carboplatin/administration & dosage , Carcinoma, Large Cell/pathology , Carcinoma, Neuroendocrine/pathology , Everolimus/administration & dosage , Female , Humans , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Metastasis , Paclitaxel/administration & dosage , Prospective Studies
16.
Pneumologie ; 71(2): 86-95, 2017 Feb.
Article in German | MEDLINE | ID: mdl-27585353

ABSTRACT

Lymphangioleiomyomatosis (LAM) is a rare multi-system disorder affecting predominantly women of childbearing age. The disease entity is divided in sporadic LAM (sLAM) and LAM associated with tuberous sclerosis complex (TSC). In up to 50 % of female TSC-patients pulmonary involvement (TSC-LAM) can be found, with first clinical symptoms usually starting between 25 and 30 years of age. Progressive deterioration of lung function of 3 - 11 % of diffusion capacity per year has been described, that's why all female TSC patients should be screened for LAM (pulmonary function testing, 6-minute walk test, high-resolution chest CT scan). MTOR inhibitors such as Everolimus or Sirolimus are implemented in the treatment of TSC/LAM and found to control disease burden. Screening for all organ manifestations in TSC is recommended and allows to improve prognosis and to prevent complications in TSC.


Subject(s)
Lung Neoplasms/diagnosis , Lymphangioleiomyomatosis/diagnosis , Respiration Disorders/diagnostic imaging , Respiratory Function Tests/methods , Tomography, X-Ray Computed/methods , Tuberous Sclerosis/diagnosis , Diagnosis, Differential , Humans , Syndrome
17.
Dtsch Med Wochenschr ; 141(S 01): S62-S69, 2016 Oct.
Article in German | MEDLINE | ID: mdl-27760452

ABSTRACT

The 2015 European Guidelines on Pulmonary Hypertension did not cover only pulmonary arterial hypertension (PAH), but also other significant subgroups of pulmonary hypertension (PH). In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany to discuss open and controversial issues surrounding the practical implementation of the European Guidelines. Several working groups were initiated, one of which was dedicated to the diagnosis and treatment of chronic thromboembolic pulmonary hypertension (CTEPH). In every patient with PH of unknown cause CTEPH should be excluded. The primary treatment option is surgical pulmonary endarterectomy (PEA) in a specialized multidisciplinary CTEPH center. Inoperable patients or patients with persistent or recurrent CTEPH after PEA are candidates for targeted drug therapy. For balloon pulmonary angioplasty (BPA), there is currently only limited experience. This option - as PEA - is reserved to specialized centers with expertise for this treatment method. In addition, a brief overview is given on pulmonary artery sarcoma, since its surgical treatment is often analogous to PEA. The recommendations of this working group are summarized in the present paper.


Subject(s)
Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/therapy , Practice Guidelines as Topic , Pulmonary Embolism/diagnosis , Pulmonary Embolism/therapy , Pulmonary Medicine/standards , Antihypertensive Agents/administration & dosage , Cardiology/standards , Drug Therapy, Combination/standards , Fibrinolytic Agents/administration & dosage , Humans , Hypertension, Pulmonary/etiology , Molecular Targeted Therapy/standards , Pulmonary Embolism/complications
18.
Lung Cancer ; 99: 117-9, 2016 09.
Article in English | MEDLINE | ID: mdl-27565924

ABSTRACT

Immunotherapy such as nivolumab is a new promising therapeutic option for advanced stage non small cell lung cancer (NSCLC). Due to the interference with the immune system previously unknown side effects are observed both in clinical studies and experience. Autoimmune phenomena effecting skin, gastrointestinal tract, endocrine glands, kidney and lung have been described. Up to now there is only limited information regarding potential cardiac side effects. We present a case of symptomatic drug induced myocarditis after nine cycles of nivolumab in a patient with efficient anticancer response.


Subject(s)
Antibodies, Monoclonal/adverse effects , Antineoplastic Agents, Immunological/adverse effects , Carcinoma, Squamous Cell/complications , Lung Neoplasms/complications , Myocarditis/diagnosis , Myocarditis/etiology , Aged , Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents, Immunological/therapeutic use , B7-H1 Antigen/metabolism , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/drug therapy , Humans , Lung Neoplasms/diagnosis , Lung Neoplasms/drug therapy , Magnetic Resonance Imaging , Male , Myocarditis/drug therapy , Neoplasm Staging , Nivolumab , Tomography, X-Ray Computed/methods
20.
Adv Exp Med Biol ; 910: 23-30, 2016.
Article in English | MEDLINE | ID: mdl-26820732

ABSTRACT

Sarcoidosis is a systemic granulomatous disease. Atherosclerosis is a chronic inflammatory vessel disease. The aim of our present study was to investigate whether sarcoidosis could be associated with increased risk of atherosclerotic vessel changes. Angiological analysis and blood tests were performed in 71 sarcoidosis patients and 12 matched controls in this prospective cross-sectional study. Specifically, angiological measurements comprised ankle brachial index (ABI), central pulse wave velocity (cPWV), pulse wave index (PWI), and duplex sonography of central and peripheral arteries. Sarcoidosis activity markers (angiotensin converting enzyme, soluble interleukin-2 receptor) and cardiovascular risk parameters such as cholesterol, lipoprotein(a), C-reactive protein, interleukin 6, fibrinogen, d-dimer, and blood count were analyzed in blood. We found no relevant differences in ABI, cPWV, and plaque burden between the sarcoidosis and control groups (1.10 ± 0.02 vs. 1.10 ± 0.02, 6.7 ± 0.5 vs. 6.1 ± 1.2, 53.7 % vs. 54.5 %, respectively). However, PWI was significantly higher in sarcoidosis patients (146.2 ± 6.8) compared with controls (104.9 ± 8.8), irrespectively of the activity of sarcoidosis and immunosuppressive medication. Except for increased lipoprotein(a) and d-dimer in sarcoidosis, the remaining cardiovascular markers were similar in both groups. We conclude that sarcoidosis is associated with increased pulse wave index, which may indicate an early stage of atherosclerosis.


Subject(s)
Atherosclerosis/physiopathology , Plaque, Atherosclerotic/physiopathology , Sarcoidosis/metabolism , Ankle Brachial Index , Atherosclerosis/diagnostic imaging , Atherosclerosis/epidemiology , Atherosclerosis/metabolism , Biomarkers/metabolism , Blood Flow Velocity , C-Reactive Protein/metabolism , Cardiovascular Diseases/diagnostic imaging , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/metabolism , Case-Control Studies , Cholesterol/metabolism , Cholesterol, HDL/metabolism , Cholesterol, LDL/metabolism , Cross-Sectional Studies , Female , Fibrin Fibrinogen Degradation Products/metabolism , Fibrinogen/metabolism , Humans , Interleukin-6/metabolism , Lipoprotein(a)/metabolism , Male , Middle Aged , Peptidyl-Dipeptidase A/metabolism , Plaque, Atherosclerotic/diagnostic imaging , Plaque, Atherosclerotic/epidemiology , Plaque, Atherosclerotic/metabolism , Prospective Studies , Pulse Wave Analysis , Receptors, Interleukin-2/metabolism , Risk Factors , Sarcoidosis/epidemiology , Ultrasonography
SELECTION OF CITATIONS
SEARCH DETAIL
...