Multicenter phase II study evaluating docetaxel and cisplatin as neoadjuvant induction regimen prior to surgery or radiochemotherapy with docetaxel, followed by adjuvant docetaxel therapy in chemonaive patients with NSCLC stage II, IIIA and IIIB (TAX-AT 1.203 Trial)
Kocher F.,Innsbruck Medical University |
Pircher A.,Innsbruck Medical University |
Mohn-Staudner A.,SMZ Otto Wagner Hospital |
Romeder F.,Paracelsus Medical University |
And 7 more authors.
Lung Cancer | Year: 2014
Objectives: Neoadjuvant therapy with a platinum based doublet is an option in NSCLC patients with upfront resectable disease. However, the role of neoadjuvant induction in stages IIIA and IIIB and in initially not resectable patients is unclear. Patients and methods: In this phase II trial, 78 patients with locally advanced NSCLC, of whom 56 were considered not resectable at initial diagnosis, were treated with three neoadjuvant cycles of docetaxel and cisplatin and subjected to radical surgery if resectable. Definitive radiochemotherapy (RCT) using weekly docetaxel was the prespecified alternative if patients were not resectable at restaging. The primary objective was response to neoadjuvant induction. Results: After induction, 36 (46%) were radically operated and 24 (31%) were treated with RCT. Overall, 32 patients (41%) completed the entire study plan. Partial response to induction therapy was observed in 43 patients (55%); furthermore, 19 of 56 initially not resectable cases (34%) became resectable upon induction. Median progression-free (PFS) and overall survival (OS) were 8.5 and 16.4 months for the whole cohort. Encouragingly, conversion to resectability was predictive for favorable outcome. On the other hand, patients who were not resectable at restaging and received RCT were characterized by a rather unfavorable prognosis (5-year and 10-year OS, whole cohort: 20% and 12%; RCT: 8% and 0%; surgery: 37% and 24%, respectively). Conclusion: Neoadjuvant induction with the doublet docetaxel/cisplatin and subsequent radical resection resulted in favorable survival. Of note, conversion to resectability was mandatory for the chance of cure in patients considered initially not resectable. © 2014 Elsevier Ireland Ltd.
Lanowska M.,Charite - Medical University of Berlin |
Kohler C.,Charite - Medical University of Berlin |
Oppelt P.,General Hospital of Linz |
Schmittel A.,Charite - Medical University of Berlin |
And 4 more authors.
Journal of Perinatal Medicine | Year: 2011
Introduction: Cervical cancer in second trimester of pregnancy is an oncologic challenge. Cisplatin is recommended to prevent cancer progression. This is a series correlating in vivo cisplatin concentration in the fetomaternal compartment and in breast milk with child development. Methods: Eight consecutive patients with cervical cancer diagnosed during the second trimester underwent conization/biopsy and/or pelvic laparoscopic lymphadenectomy (LAE). Delay of pregnancy in combination with neoadjuvant monochemotherapy was performed. After 2-4 cycles of cisplatin monochemotherapy cesarean section followed by radical hysterectomy was performed above 31 weeks of gestation. Synchronous samples from maternal blood, umbilical cord blood, and amniotic fluid were taken and analyzed. A probe of breast milk was taken from three patients. Pediatric aftercare was done every three months postpartum. Results: Laparoscopic LAE was uncomplicated in all patients. In seven out of eight patients lymph nodes were tumor free. Nine healthy babies were delivered. Pediatric follow-up showed normal development. Cisplatin concentrations in the umbilical cord and amniotic fluid were 31-65% and 13-42% of the amount in maternal blood, respectively. In breast milk, cisplatin was detectable in 1-10% of maternal blood concentration. Conclusion: Knowledge of significant lower cisplatin concentrations in fetal compartment and normal child growth provides additional security to apply cisplatin in pregnancy. Breastfeeding cannot be recommended. Copyright © by Walter de Gruyter - Berlin - New York.
Rudas M.,Medical University of Vienna |
Dietze O.,University of Salzburg |
Luisser I.,Hospital Guessing |
Klug E.,Hospital of Oberwart |
And 8 more authors.
Annals of Oncology | Year: 2013
Background: In early estrogen receptor (ER)-positive/HER2-negative breast cancer, the decision to administer chemotherapy is largely based on prognostic criteria. The combined molecular/clinical EndoPredict test (EPclin) has been validated to accurately assess prognosis in this population. In this study, the clinical relevance of EPclin in relation to well-established clinical guidelines is assessed. Patients and methods: We assigned risk groups to 1702 ER-positive/HER2-negative postmenopausal women from two large phase III trials treated only with endocrine therapy. Prognosis was assigned according to National Comprehensive Cancer Center Network-, German S3-, St Gallen guidelines and the EPclin. Prognostic groups were compared using the Kaplan-Meier survival analysis. Results: After 10 years, absolute risk reductions (ARR) between the high- and low-risk groups ranged from 6.9% to 11.2% if assigned according to guidelines. It was at 18.7% for EPclin. EPclin reassigned 58%-61% of women classified as high-/intermediate-risk (according to clinical guidelines) to low risk. Women reclassified to low risk showed a 5% rate of distant metastasis at 10 years. Conclusion: The EPclin score is able to predict favorable prognosis in a majority of patients that clinical guidelines would assign to intermediate or high risk. EPclin may reduce the indications for chemotherapy in ER-positive postmenopausal women with a limited number of clinical risk factors. © The Author 2012.
Cetin H.,Medical University of Vienna |
Rath J.,Medical University of Vienna |
Fuzi J.,Unit for Health Care Economics |
Reichardt B.,Unit for Health Care Economics |
And 10 more authors.
Neuroepidemiology | Year: 2015
Objectives: To assess the epidemiology of ALS in Austria and to evaluate the long-term effect of riluzole treatment on survival. Methods: Hospital discharge and riluzole prescription databases were used to identify ALS cases from January 2008 to June 2012. Using the capture-recapture method we evaluated the incidence and prevalence of ALS and patients' survival in dependence of age, gender and riluzole treatment. Results: The corrected incidence and prevalence of ALS were 3.13/100,000 person-years (95% CI, 2.77 to 3.50) and 9.14/100,000 persons (95% CI, 8.53 to 9.79), respectively. Median survival from diagnosis was 676 days (95% CI, 591 to 761). A younger age at diagnosis was associated with a longer survival. Gender did not appear to affect survival time. Riluzole therapy was associated with a survival advantage only for the initial treatment period. The adjusted hazard ratio of mortality for using riluzole increased continually over time resulting in an apparent reversal of its beneficial effect after 6 months of therapy. Conclusions: We report incidence and prevalence estimates that are on the upper end of the wide range discussed in literature. Riluzole seems to exert a beneficial effect only in the first 6 months of therapy. © 2015 S. Karger AG, Basel.
Dubsky P.,Medical University of Vienna |
Brase J.C.,Sividon Diagnostics |
Jakesz R.,Medical University of Vienna |
Rudas M.,Medical University of Vienna |
And 16 more authors.
British Journal of Cancer | Year: 2013
Background:ER+/HER2-breast cancers have a proclivity for late recurrence. A personalised estimate of relapse risk after 5 years of endocrine treatment can improve patient selection for extended hormonal therapy.Methods:A total of 1702 postmenopausal ER+/HER2-breast cancer patients from two adjuvant phase III trials (ABCSG6, ABCSG8) treated with 5 years of endocrine therapy participated in this study. The multigene test EndoPredict (EP) and the EPclin score (which combines EP with tumour size and nodal status) were predefined in independent training cohorts. All patients were retrospectively assigned to risk categories based on gene expression and on clinical parameters. The primary end point was distant metastasis (DM). Kaplan-Meier method and Cox regression analysis were used in an early (0-5 years) and late time interval (>5 years post diagnosis).Results:EP is a significant, independent, prognostic parameter in the early and late time interval. The expression levels of proliferative and ER signalling genes contribute differentially to the underlying biology of early and late DM. The EPclin stratified 64% of patients at risk after 5 years into a low-risk subgroup with an absolute 1.8% of late DM at 10 years of follow-up.Conclusion:The EP test provides additional prognostic information for the identification of early and late DM beyond what can be achieved by combining the commonly used clinical parameters. The EPclin reliably identified a subgroup of patients who have an excellent long-term prognosis after 5 years of endocrine therapy. The side effects of extended therapy should be weighed against this projected outcome. © 2013 Cancer Research UK.