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Golnik, Slovenia

Knez L.,University Hospital Golnik | Kosnik M.,University Hospital Golnik | Ovcaricek T.,University of Maribor | Sadikov A.,University of Ljubljana | And 3 more authors.
Journal of Cancer Research and Clinical Oncology | Year: 2012

Purpose: Multiple drug resistance limits the efficacy of numerous cytotoxic drugs used in the treatment of small cell lung cancer (SCLC). The drug efflux protein ATP-binding cassette transporter B1 (ABCB1) has an important role in this process, and its gene variability may affect chemotherapy outcomes. Patients and methods: This study aimed to evaluate the associations between ABCB1 polymorphisms G2677T/A, C3435T, and their haplotype with progression-free survival (PFS) and overall survival (OS) in 177 SCLC patients treated with cisplatin-etoposide or cyclophosphamide-epirubicin-vincristine chemotherapy. To determine the ABCB1 genotype, allelic speciWc TaqMan® probes were used in a RT-PCR. Results: Patients carrying the G2677T/A TT + TA + AA genotypes (24 %) or the C3435T CT + TT genotypes (72 %) or the 2677T/A-3435T haplotype (40 %) had a longer PFS (Cox regression, P = 0.052, 0.037 and 0.037, respectively); these associations persisted also in multivariate analyses (Cox regression, P = 0.028, 0.037 and 0.030, respectively). Moreover, patients with the C3435T CT + TT genotypes had a longer OS both in univariate and multivariate analysis (Cox regression, P = 0.022 and 0.028, respectively). A trend toward longer OS was noted for the 2677T/A-3435T haplotype (Cox regression, P = 0.051), but its independent value was not confirmed (Cox regression, P = 0.071). Conclusions: Our study reported a possible predictive value of ABCB1 polymorphisms G2677T/A, C3435T, and their haplotype for longer PFS and OS in Caucasian SCLC patients treated with chemotherapy. However, to be implemented into routine clinical practice, ABCB1 polymorphisms require further validation. © Springer-Verlag 2012.

Gelbrich G.,University of Leipzig | Edelmann F.,University of Gottingen | Inkrot S.,Charite - Medical University of Berlin | Lainscak M.,Charite - Medical University of Berlin | And 9 more authors.
International Journal of Cardiology | Year: 2012

Background: Guideline-recommended beta-blocker (BB) target doses for patients with chronic heart failure can often not be reached. This secondary analysis of the CIBIS-ELD trial was carried out to better understand reasons for not achieving target doses. Methods: Changes in heart rate (HR) and other parameters during a 12-week up-titration period in 302 BB naïve patients were evaluated in the subgroups achieving 12.5, 25, 50, and 100% of the target dose (groups 1, 2, 3, and 4, respectively). Results: Achieved doses predominantly depended on baseline HR (means 68, 74, 76, and 84 bpm in groups 1-4, respectively, Pb0.001). HR was consistently reduced with each dose level to 65, 63, and 62 bpm in groups 1-3 and to 71 bpm in group 4 (Pb0.001). When adjusted for baseline, HR reduction achieved in group 3 was better than in group 4 (difference -5.4 bpm, Pb0.05). More patients in groups 3/4 than in groups 1/2 improved in NYHA class (P=0.01). NTproBNP increased by 38% in group 4 (Pb0.01) but not in the others (Pb0.05 between groups). Changes in blood pressure, six-minute walk distance and self-rated health were comparable in all groups. Conclusions: The desired effect of HR reduction appears to be a predominant limitation for BB up-titration. Vice versa, achieving the target dose may be a sign of insufficient response rather than successful treatment. In view of these results and the well-known importance of HR for survival, not target doses, but HR control should be given priority in BB treatment for heart failure. © 2010 Elsevier Ireland Ltd. All rights reserved.

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