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Schultheis B.,University of Bochum Marienhospital Herne | Schultheis B.,Ruhr University Bochum | Strumberg D.,University of Bochum Marienhospital Herne | Bergmann L.,Goethe University Frankfurt | And 7 more authors.
Investigational New Drugs | Year: 2012

Purpose S-1, an oral fluoropyrimidine derivative, has previously demonstrated anticancer efficacy in pancreatic cancer (PC), predominantly in Asian populations. This study evaluated the antitumor effect and safety of S-1 in Caucasian patients with metastatic PC. Methods Chemotherapy-naïve patients received S-1 orally at 30 mg/m2 twice daily (BID) for 2 weeks, repeated every 3 weeks. Primary endpoint was ORR. Secondary endpoints included PFS, OS and safety assessment. The trial had a Simon's twostage design with 22 patients evaluable for efficacy in stage 1 and an additional 18 patients in stage 2, if =3/22 patients had a confirmed response at the first stage. Results Three out of 27 patients showed PR, however, detection of asymptomatic brain metastases in one of them prevented this study from proceeding to stage 2. The median PFS and OS for all patients was 3.5 and 9.1 months, respectively. The median duration of disease control for patients with SD or PR (n=17) was 4.3 months. S-1 was well tolerated; fatigue was the most frequent grade 3/4 adverse event. Conclusions Efficacy data of PFS and OS are at least comparable to gemcitabine, the current standard of care. S-1 is active in Caucasian patients with metastatic PC. © 2012 Springer Science+Business Media, LLC. Source

Schultheis B.,University of Bochum Marienhospital Herne | Kummer G.,University of Bochum Marienhospital Herne | Zeth M.,University of Bochum Marienhospital Herne | Brendel E.,Bayer AG | And 3 more authors.
Cancer Chemotherapy and Pharmacology | Year: 2012

Purpose: Sorafenib (BAY 43-9006), a multikinase inhibitor, has been shown to inhibit tumor growth and tumor angiogenesis by targeting Raf kinase, vascular endothelial growth factor receptor, and platelet-derived growth factor receptor. This study investigated the safety, pharmacokinetics, and preliminary efficacy of sorafenib in combination with gemcitabine and cisplatin. Methods: Patients with advanced solid tumors were treated with 75 mg/m 2 cisplatin on day 1 and 1,250 mg/m 2 gemcitabine on days 1 and 8 of each 21-day cycle. On day 5 of cycle 1, sorafenib 400 mg twice daily was started and continued throughout the complete treatment cycles without interruption. Results: Nineteen patients were valid for safety analysis. The most frequent toxicities related to the cytotoxic agents were hematological disorders. Sorafenib-related toxicities were skin-related, gastrointestinal, and constitutional symptoms. No clinically relevant pharmacokinetic drug-drug interaction between sorafenib, cisplatin, and gemcitabine was detected. AUC 0-72 and C max of total and unbound platinum were only marginally changed by concomitant sorafenib. Concomitant sorafenib increased mean AUC and C max of gemcitabine by 12 and 21%. Conclusions: Sorafenib as continuous oral treatment in combination with gemcitabine and cisplatin demonstrated an acceptable safety profile. No clinically relevant pharmacokinetic interaction was detected. Preliminary antitumor activity, pharmacokinetic, and safety data support the recommendation of 400 mg sorafenib twice daily in combination with cisplatin and gemcitabine to be further evaluated in clinical studies. © 2011 Springer-Verlag. Source

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