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Kellokumpu-Lehtinen P.-L.,University of Tampere | Hjalm-Eriksson M.,Karolinska University Hospital | Thellenberg-Karlsson C.,Umea University | Astrom L.,Uppsala University Hospital | And 5 more authors.
Prostate Cancer and Prostatic Diseases | Year: 2012

Background: Radical radiotherapy (RT) combined with androgen deprivation therapy is currently the standard treatment for elderly patients with localized intermediate- or high-risk prostate cancer (PC). To increase the recurrence-free and overall survival, we conducted an adjuvant, randomized trial using docetaxel (T) in PC patients (Scandinavian Prostate Cancer Group trial 13). Methods: The inclusion criteria are the following: Men >18 and ≤75 years of age, WHO/ECOG performance status 0-1, histologically proven PC within 12 months before randomization and one of the following: T2, Gleason 7 (4+3), PSA > 10; T2, Gleason 8-10, any PSA; or any T3 tumors. Neoadjuvant/adjuvant hormone therapy is mandatory for all patients. The patients were randomized to receive six cycles of T (75 mg m-2 d 1. cycle 21 d) or no docetaxel after radical RT (with a minimum tumor dose of 74 Gy). This study identifier number is NTC 006653848 (http://www.clinicaltrials.org). Results: In this preplanned safety analysis of 100 patients, T treatment induced grade (G) 3 adverse events (AEs) in 15 patients (30%) and G4 AEs in 30 patients (60%), mainly due to bone marrow toxicity. Neutropenia G3-4 was observed in 72% of the patients, febrile neutropenia was found in 24% of patients, neutropenic infection in 10% of patients and G3 infection without neutropenia in 4% of patients. Nonhematological G3 AEs were rare: Anorexia, diarrhea, mucositis, nausea, pain (1 patient each) and fatigue (5). Other severe serious AEs related to T were pulmonary embolism and renal failure. However, only three patients discontinued T before completing the planned six cycles. No deaths had occurred. No patients in the control arm experienced G3-4 toxicities at 12 weeks after the randomization. Conclusions: Adjuvant docetaxel chemotherapy after radiotherapy has a higher frequency of neutropenia than previous studies on patients with metastatic disease. Otherwise, the treatment was quite well tolerated. © 2012 Macmillan Publishers Limited All rights reserved.

Joensuu H.,University of Helsinki | Sperinde J.,Monogram Biosciences | Leinonen M.,4Pharma | Huang W.,Monogram Biosciences | And 11 more authors.
Annals of Oncology | Year: 2011

Background: It is unknown how a very high tumor total HER2 (human epidermal growth factor receptor-2) content (H2T) influences outcome in early breast cancer treated with adjuvant trastuzumab plus chemotherapy. Patients and methods: H2T was measured using a novel quantitative assay (HERmark®) from formalin-fixed tumor tissue of 899 women who participated in the FinHer trial (ISRCTN76560285). In a chromogenic in situ hybridization (CISH) test, 197 (21.9%) patients had HER2-positive cancer and were randomly assigned to receive trastuzumab or control. Results: Cancer H2T levels varied 1808-fold. High H2T levels were correlated with a positive HER2 status by CISH (P < 0.0001). A nonlinear association was present between H2T and the hazard of distant recurrence in a subpopulation treatment effect pattern plot analysis in CISH-positive disease. Patients with very high H2T (defined by ≥ 22-fold the median of HER2-negative cancers; 13% of CISH-positive cancers) did not benefit from adjuvant trastuzumab [hazard ratio (HR) 1.23; 95% confidence interval (CI) 0.33-4.62; P = 0.75], whereas the rest of the patients with HER2-positive disease by CISH (87%) did benefit (HR 0.52; 95% CI 0.28-1.00; P = 0.050). Conclusion: Patients with HER2-positive breast cancer with very high tumor HER2 content may benefit less from adjuvant trastuzumab compared with those whose cancer has more moderate HER2 content. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Eggert K.,University of Marburg | Skogar O.,Lanssjukhuset Ryhov | Amar K.,Royal Bournemouth Hospital | Luotonen L.,Orion Pharma | And 5 more authors.
Journal of Neural Transmission | Year: 2010

The study objective was to assess the efficacy, safety and feasibility of switching from levodopa/benserazide (LB) or levodopa/carbidopa (LC) to levodopa/carbidopa/entacapone (LCE) in Parkinson's disease (PD) patients with wearing-off. This was a multicenter, openlabel, 6-week study; the primary outcome was success rate based on the patient-assessed Clinical Global Impression of Change (P-CGI-C). Secondary outcomes included investigator- assessed CGI-C (I-CGI-C), change from baseline in Unified Parkinson's Disease Rating Scale (UPDRS), motor/non-motor wearing-off symptoms and quality of life-visual analog scale (QoL-VAS). After switching to LCE, 77% of patients reported an 'improvement' (p < 0.0001 vs. patients reporting 'no change or worsening'). Significant improvements were seen in I-CGI-C, UPDRS and QoLVAS, regardless of prior therapy. Oral levodopa dosing was increased in 28% of patients; the primary outcome remained significant when these patients were excluded. The data suggest that switching from LB/LC to LCE provided a significant benefit in PD patients with wearing-off. © Springer-Verlag 2010.

Melamies M.,University of Helsinki | Vainio O.,University of Helsinki | Spillmann T.,University of Helsinki | Junnila J.,4Pharma | Rajamaki M.M.,University of Helsinki
Veterinary Journal | Year: 2012

Orally administered corticosteroids are commonly used to treat chronic respiratory disease, but adverse effects suggest that the inhalation route may be safer. To compare the systemic effects of inhaled and oral corticosteroids, a prospective, randomised, placebo-controlled cross-over study was conducted. Six healthy neutered female Beagle dogs were randomly allocated to four treatment groups: (1) budesonide inhalation (200. μg twice daily); (2) fluticasone inhalation (250. μg twice daily); (3) oral prednisolone (1. mg/kg once daily); and (4) placebo inhalation (room air twice daily). Each treatment and wash-out period lasted 4. weeks. The endocrine status of each dog was assessed on days 0, 28 and 35 using the adrenocorticotropic hormone (ACTH) stimulation test. The effects of treatments were assessed using a linear mixed effects model.After the 4. week treatment period, a significant decrease was observed in the basal serum cortisol level of the prednisolone group (P< 0.03), and a decrease was also seen in the ACTH-stimulated peak cortisol levels of both the prednisolone and fluticasone groups (P< 0.001), compared with the budesonide group in which no suppression was detected. The results showed that cortisol production in dogs was strongly suppressed by oral prednisolone and by inhaled fluticasone. © 2012 Elsevier Ltd.

Rudolph G.,Ludwig Maximilians University of Munich | Dimitriadis K.,Ludwig Maximilians University of Munich | Buchner B.,Ludwig Maximilians University of Munich | Heck S.,Ludwig Maximilians University of Munich | And 6 more authors.
Journal of Neuro-Ophthalmology | Year: 2013

Background: The authors investigated the correlation of protan and tritan color vision with disease characteristics in Leber hereditary optic neuropathy (LHON). The authors also characterized the therapeutic potential of idebenone in protecting patients from developing dyschromatopsia in LHON. Methods: Color contrast data of 39 LHON patients participating in a randomized, double-blind placebo-controlled intervention study were evaluated. Patients reported disease onset <5 years before enrolment and were genetically confirmed. Protan and tritan color contrast sensitivity was measured using a computer graphics method in patients receiving idebenone (Catena; 900 mg/d; N = 28) or placebo (N = 11) for 6 months. Results: Mean age of patients was 28.1 years, 87.2% were men, 76.9% carried the m11778G>A mutation, and mean duration since onset was 2 years. Assessing protan and tritan color vision at baseline revealed a high degree of color confusion even in young patients (<25 years) and with a short history of disease (<1 year). Treatment with idebenone improved tritan color vision compared with placebo (P = 0.008 at week 24); a similar trend was seen for protan. The effect of idebenone was most prominent in patients with discordant visual acuity (interocular difference of logMAR >0.2). In this subgroup, the treatment effect at week 24 was 20.4% (P = 0.005) in favor of idebenone for the tritan color domain and 13.5% (P = 0.067) for the protan domain. Conclusion: This study confirms that protan and tritan color confusion is an early symptom in LHON. Treatment with idebenone can protect from loss of color vision, particularly in patients who are at imminent risk of further vision loss. © 2012 by North American Neuro-Ophthalmology Society.

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