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1.
Pneumologie ; 75(10): 776-794, 2021 Oct.
Article in German | MEDLINE | ID: mdl-33946118

ABSTRACT

Asbestos-related mesotheliomas belong to the group of the most frequent occupational diseases in Germany, reaching about 1,000 new cases per year. The disease has a dismal prognosis because most tumors remain asymptomatic for a long time and therefore are diagnosed as incidental findings at later stages.During the last decade the German Social Accident Insurance (DGUV) has made considerable efforts to prepone the diagnosis in order to detect the disease at earliest possible stages. These efforts resulted in new findings showing that, in a high-risk group, a combination of the biomarkers calretinin and mesothelin was able to advance the diagnosis up to 12 months.Ideally, the diagnosis of a mesothelioma at an early stage has to be accompanied by the best possible individualized therapy. Standard therapeutic strategies are surgery and chemotherapy, added by radiotherapy and psycho-oncology. In recent years, several new therapeutic avenues are being explored. This review comprehensively presents both old and new therapeutic options in mesothelioma, based on international Leitlinien and new studies.


Subject(s)
Asbestos , Lung Neoplasms , Mesothelioma, Malignant , Mesothelioma , Occupational Exposure , Pleural Neoplasms , Asbestos/adverse effects , Consensus , Humans , Lung Neoplasms/diagnosis , Lung Neoplasms/therapy , Mesothelioma/diagnosis , Mesothelioma/therapy , Pleural Neoplasms/diagnosis , Pleural Neoplasms/therapy
3.
Ann Oncol ; 28(12): 3028-3036, 2017 Dec 01.
Article in English | MEDLINE | ID: mdl-29045535

ABSTRACT

BACKGROUND: Combination of selumetinib plus docetaxel provided clinical benefit in a previous phase II trial for patients with KRAS-mutant advanced non-small-cell lung cancer (NSCLC). The phase II SELECT-2 trial investigated safety and efficacy of selumetinib plus docetaxel for patients with advanced or metastatic NSCLC. PATIENTS AND METHODS: Patients who had disease progression after first-line anti-cancer therapy were randomized (2 : 2 : 1) to selumetinib 75 mg b.i.d. plus docetaxel 60 or 75 mg/m2 (SEL + DOC 60; SEL + DOC 75), or placebo plus docetaxel 75 mg/m2 (PBO + DOC 75). Patients were initially enrolled independently of KRAS mutation status, but the protocol was amended to include only patients with centrally confirmed KRAS wild-type NSCLC. Primary end point was progression-free survival (PFS; RECIST 1.1); statistical analyses compared each selumetinib group with PBO + DOC 75 for KRAS wild-type and overall (KRAS mutant or wild-type) populations. RESULTS: A total of 212 patients were randomized; 69% were KRAS wild-type. There were no statistically significant improvements in PFS or overall survival for overall or KRAS wild-type populations in either selumetinib group compared with PBO + DOC 75. Overall population median PFS for SEL + DOC 60, SEL + DOC 75 compared with PBO + DOC 75 was 3.0, 4.2, and 4.3 months, HRs: 1.12 (90% CI: 0.8, 1.61) and 0.92 (90% CI: 0.65, 1.31), respectively. In the overall population, a higher objective response rate (ORR; investigator assessed) was observed for SEL + DOC 75 (33%) compared with PBO + DOC 75 (14%); odds ratio: 3.26 (90% CI: 1.47, 7.95). Overall the tolerability profile of SEL + DOC was consistent with historical data, without new or unexpected safety concerns identified. CONCLUSION: The primary end point (PFS) was not met. The higher ORR with SEL + DOC 75 did not translate into prolonged PFS for the overall or KRAS wild-type patient populations. No clinical benefit was observed with SEL + DOC in KRAS wild-type patients compared with docetaxel alone. No unexpected safety concerns were reported. TRIAL IDENTIFIER: Clinicaltrials.gov NCT01750281.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Benzimidazoles/administration & dosage , Benzimidazoles/adverse effects , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Disease-Free Survival , Docetaxel , Double-Blind Method , Female , Humans , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Metastasis , Proto-Oncogene Proteins p21(ras)/genetics , Taxoids/administration & dosage , Taxoids/adverse effects
4.
Pneumologie ; 70(9): 579-88, 2016 Sep.
Article in German | MEDLINE | ID: mdl-27603946

ABSTRACT

PURPOSE: Assessment of several clinical factors on progression-free (PFS) and overall survival (OS) in NSCLC patients (pts.) (stage IV) with mutated epidermal growth factor receptor (EGFRm+) treated with gefitinib (gef) or with chemotherapy (CT) under real-world conditions. METHODS: 285 EGFRm+ pts. of the non-interventional REASON study treated with gef (n = 206) or CT (n = 79) as first-line therapy or with gef (n = 213) or CT (n = 61) in any line throughout the course of therapy were analyzed according to age, gender, smoking history and histology. RESULTS: Compared with CT, patients treated with gef showed prolongation of PFS and OS in all subgroups. PFS was significantly increased in women and non-smokers. OS was significantly increased in women, non-smokers, (ex)-smokers, patients with adenocarcinoma and elderly patients when treated with gef compared to CT. Female gender turned out to be an independent positive predictive factor for OS in patients treated with gef (HRmale: 1.74, p = 0.0009). CONCLUSION: A clinical benefit of gef was shown for all analyzed clinical subgroups of EGFRm+ pts. This was confirmed for the female gender in a multivariate analysis.


Subject(s)
Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/mortality , Lung Neoplasms/drug therapy , Lung Neoplasms/mortality , Quinazolines/administration & dosage , Smoking/epidemiology , Adult , Age Distribution , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/diagnosis , Disease-Free Survival , ErbB Receptors/genetics , Female , Gefitinib , Germany/epidemiology , Humans , Lung Neoplasms/genetics , Male , Middle Aged , Prevalence , Risk Factors , Sex Distribution , Survival Analysis , Treatment Outcome
5.
Br J Cancer ; 113(1): 12-9, 2015 Jun 30.
Article in English | MEDLINE | ID: mdl-26086878

ABSTRACT

BACKGROUND: We report final results with extended follow-up from a global, expanded-access trial that pre-regulatory approval provided sunitinib to metastatic renal cell carcinoma (mRCC) patients, ineligible for registration-directed trials. METHODS: Patients ⩾18 years received oral sunitinib 50 mg per day on a 4-weeks-on-2-weeks-off schedule. Safety was assessed regularly. Tumour measurements were scheduled per local practice. RESULTS: A total of 4543 patients received sunitinib. Median treatment duration and follow-up were 7.5 and 13.6 months. Objective response rate was 16% (95% confidence interval (CI): 15-17). Median progression-free survival (PFS) and overall survival (OS) were 9.4 months (95% CI: 8.8-10.0) and 18.7 months (95% CI: 17.5-19.5). Median PFS in subgroups of interest: aged ⩾65 years (33%), 10.1 months; Eastern Cooperative Oncology Group performance status ⩾2 (14%), 3.5 months; non-clear cell histology (12%), 6.0 months; and brain metastases (7%), 5.3 months. OS was strongly associated with the International Metastatic Renal-Cell Carcinoma Database Consortium prognostic model (n=4065). The most common grade 3/4 treatment-related adverse events were thrombocytopenia (10%), fatigue (9%), and asthenia, neutropenia, and hand-foot syndrome (each 7%). CONCLUSION: Final analysis of the sunitinib expanded-access trial provided a good opportunity to evaluate the long-term side effects of a tyrosine kinase inhibitor used worldwide in mRCC. Efficacy and safety findings were consistent with previous results.


Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Renal Cell/drug therapy , Indoles/therapeutic use , Kidney Neoplasms/drug therapy , Neoplasm Metastasis , Pyrroles/therapeutic use , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/adverse effects , Carcinoma, Renal Cell/pathology , Female , Humans , Indoles/adverse effects , Kidney Neoplasms/pathology , Male , Middle Aged , Pyrroles/adverse effects , Sunitinib , Young Adult
6.
Ann Oncol ; 26(8): 1573-88, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25897013

ABSTRACT

To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines of treatment in advanced disease, early-stage disease and locally advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on locally advanced disease.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/therapy , Lung Neoplasms/therapy , Lung , Bronchoscopy , Carboplatin/administration & dosage , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/pathology , Chemotherapy, Adjuvant , Cisplatin/administration & dosage , Disease Management , Endoscopic Ultrasound-Guided Fine Needle Aspiration , Etoposide/administration & dosage , Europe , Humans , Lung/diagnostic imaging , Lung/pathology , Lung Neoplasms/diagnosis , Lung Neoplasms/pathology , Lymph Nodes/pathology , Mediastinum , Multimodal Imaging , Pneumonectomy , Positron-Emission Tomography , Radiotherapy, Adjuvant , Societies, Medical , Tomography, X-Ray Computed , Vinblastine/administration & dosage , Vinblastine/analogs & derivatives , Vinorelbine
8.
Br J Cancer ; 107(5): 823-30, 2012 Aug 21.
Article in English | MEDLINE | ID: mdl-22836512

ABSTRACT

BACKGROUND: Tubulin-binding agents (TBAs) are effective in non-small cell lung cancer (NSCLC) treatment. Both ßIII- and ßV-tubulins are expressed by cancer cells and may lead to resistance against TBAs. METHODS: Pre-treatment samples from 65 locally advanced or oligometastatic NSCLC patients, who underwent uniform induction chemotherapy with paclitaxel and platinum followed by radiochemotherapy with vinorelbine and platinum were retrospectively analysed by immunohistochemistry. Protein expression of ßIII- and ßV-tubulin was morphometrically quantified. RESULTS: Median pre-treatment H-score for ßIII-tubulin was 110 (range: 0-290), and 160 for ßV-tubulin (range: 0-290). Low ßIII-tubulin expression was associated with improved overall survival (OS) (P=0.0127, hazard ratio (HR): 0.328). An association between high ßV-tubulin expression and prolonged progression-free survival (PFS, median 19.2 vs 9.4 months in high vs low expressors; P=0.0315, HR: 1.899) was found. Further, high ßV-tubulin expression was associated with objective response (median H-score 172.5 for CR+PR vs 120 for SD+PD patients, P=0.0104) or disease control following induction chemotherapy (170 for CR+PR+SD vs 100 for PD patients, P=0.0081), but not radiochemotherapy. CONCLUSION: Expression of ßV-tubulin was associated with treatment response and PFS following paclitaxel-based chemotherapy of locally advanced and oligometastatic NSCLC patients. Prolonged OS was associated with low levels of ßIII-tubulin. Prospective evaluation of ßIII/ßV-tubulin expression in NSCLC is warranted.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/metabolism , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , Tubulin/biosynthesis , Adult , Aged , Bridged-Ring Compounds/administration & dosage , Carcinoma, Non-Small-Cell Lung/pathology , Cohort Studies , Disease-Free Survival , Female , Humans , Immunohistochemistry , Lung Neoplasms/pathology , Male , Middle Aged , Retrospective Studies , Taxoids/administration & dosage , Transfection , Treatment Outcome , Tubulin/genetics
9.
Lung Cancer ; 77(2): 376-82, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22498112

ABSTRACT

The FLEX study demonstrated that the addition of cetuximab to chemotherapy significantly improved overall survival in the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC). In the FLEX intention to treat (ITT) population, we investigated the prognostic significance of particular baseline characteristics. Individual patient data from the treatment arms of the ITT population of the FLEX study were combined. Univariable and multivariable Cox regression models were used to investigate variables with potential prognostic value. The ITT population comprised 1125 patients. In the univariable analysis, longer median survival times were apparent for females compared with males (12.7 vs 9.3 months); patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 compared with 1 compared with 2 (13.5 vs 10.6 vs 5.9 months); never smokers compared with former smokers compared with current smokers (14.6 vs 11.1 vs 9.0); Asians compared with Caucasians (19.5 vs 9.6 months); patients with adenocarcinoma compared with squamous cell carcinoma (12.4 vs 9.3 months) and those with metastases to one site compared with two sites compared with three or more sites (12.4 months vs 9.8 months vs 6.4 months). Age (<65 vs ≥65 years), tumor stage (IIIB with pleural effusion vs IV) and percentage of tumor cells expressing EGFR (<40% vs ≥40%) were not identified as possible prognostic factors in relation to survival time. In multivariable analysis, a stepwise selection procedure identified age (<65 vs ≥65 years), gender, ECOG PS, smoking status, region, tumor histology, and number of organs involved as independent factors of prognostic value. In summary, in patients with advanced NSCLC enrolled in the FLEX study, and consistent with previous analyses, particular patient and disease characteristics at baseline were shown to be independent factors of prognostic value. The FLEX study is registered with ClinicalTrials.gov, number NCT00148798.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Aged , Aged, 80 and over , Antibodies, Monoclonal , Antibodies, Monoclonal, Humanized , Carcinoma, Non-Small-Cell Lung/mortality , Cetuximab , Female , Humans , Lung Neoplasms/mortality , Male , Middle Aged , Neoplasm Staging , Prognosis , Risk Factors , Treatment Outcome
10.
Ann Oncol ; 23(3): 678-687, 2012 Mar.
Article in English | MEDLINE | ID: mdl-21617019

ABSTRACT

BACKGROUND: The objective of this multicenter, prospective uncontrolled phase II trial was to determine efficacy, safety and tolerability of vatalanib, an oral angiogenesis inhibitor targeting all known vascular endothelial growth factor receptors, in the second-line treatment of non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with stage IIIB/IV NSCLC-proven tumor progression during or after one platinum-based chemotherapy regimen received a fixed dose of 1250 mg vatalanib either once-daily dosing (QD) or two divided daily dosing (TDD: 500 mg a.m. + 750 mg p.m.) until disease progression or unacceptable toxicity. Primary end point was the disease control rate (DCR) at 12 weeks. RESULTS: Fifty-four and 58 patients were enrolled to the QD and TDD arms. DCR at 12 weeks was 35% in the QD and 37% in the TDD arm. The best overall response included one (2%) patient with confirmed partial response with QD and three (5%) with TDD. Median progression-free survival and overall survival were 2.1/7.3 months in the QD arm and 2.8/9.0 months with TDD arm. This therapy showed a moderate toxicity profile for the majority of patients. CONCLUSIONS: In the chosen patient population, vatalanib QD and TDD dosing demonstrated potential benefits in tumor size reduction, DCR, and survival.


Subject(s)
Angiogenesis Inhibitors/administration & dosage , Antineoplastic Agents/administration & dosage , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Phthalazines/administration & dosage , Pyridines/administration & dosage , Angiogenesis Inhibitors/adverse effects , Antineoplastic Agents/adverse effects , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Disease-Free Survival , Dose-Response Relationship, Drug , Female , Humans , Kaplan-Meier Estimate , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Neoplasm Staging , Phthalazines/adverse effects , Pyridines/adverse effects , Recurrence , Salvage Therapy/methods
11.
Ann Oncol ; 22(8): 1798-804, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21266516

ABSTRACT

BACKGROUND: This trial was designed to prove superiority of irinotecan over etoposide combined with carboplatin in extensive-disease small-cell lung cancer. PATIENTS AND METHODS: Patients were randomly assigned to receive carboplatin area under the curve 5 mg x min/ml either in combination with irinotecan 50 mg/m2 on days 1, 8, and 15 (IP) or etoposide 140 mg/m2 on days 1-3 (EP). Primary end point was progression-free survival (PFS) at 6 months. Secondary end points were overall survival (OS), response rate, and toxicity. RESULTS: Of 226 patients, 216 were eligible. Median PFS was 6.0 months [95% confidence interval (CI) 5.0-7.0] in the IP arm and 6.0 months (95% CI 5.2-6.8) in EP arm (P = 0.07). Median survival was 10.0 months (95% CI 8.4-11.6) and 9.0 months (95% CI 7.6-10.4) in the IP and EP arm (P = 0.06), respectively. Hazard ratios for disease progression and OS were 1.29 (95% CI 0.96-1.73, P = 0.095) and 1.34 (95% CI 0.97-1.85, P = 0.072), respectively. No difference in response rates was observed. Grade 3 and 4 hematologic toxicity favored the IP arm, whereas diarrhea was significantly more frequent in the IP arm. CONCLUSION: This trial failed to show superiority of irinotecan over etoposide in combination with carboplatin.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Camptothecin/analogs & derivatives , Carboplatin/therapeutic use , Etoposide/therapeutic use , Lung Neoplasms/drug therapy , Small Cell Lung Carcinoma/drug therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Camptothecin/administration & dosage , Camptothecin/therapeutic use , Carboplatin/administration & dosage , Disease-Free Survival , Etoposide/administration & dosage , Female , Germany , Humans , Irinotecan , Lung Neoplasms/pathology , Male , Middle Aged , Small Cell Lung Carcinoma/pathology
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