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February 15, ; Accepted: October 19, ; Published: January 9, Copyright: ADS PTV-331-EF is an open-access article distributed under the terms of the Creative Commons Attribution Licensewhich permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This work was supported by Bayer http: The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Competing interests: Bayer funded this study. There are no patents, products in development or marketed products to declare.


Introduction Pancreatic cancer ranks sixth among cancer-related deaths in Europe. Treatment of patients with locally advanced disease is palliative; with current therapies, the median overall survival ranges only from 9 ADS PTV-331-EF 10 months [1].

Management options include systemic chemotherapy alone and combined forms of treatment with chemoradiation and chemotherapy. A series of randomized trials conducted over the past two decades established that chemoradiation therapy is an effective, although more toxic, approach in these patients [2]. Gemcitabine has been considered for ADS PTV-331-EF years the standard therapy for metastatic pancreatic cancer. Recently Folfirinox schedule, has replace gemcitabine as first-line therapy in fit ECOG PS 0—1 metastatic pancreatic cancer patients [3].

Gemcitabine remains a standard drug for locally unresectable pancreatic cancer in combination with radiotherapy. Previous phase ADS PTV-331-EF and II studies determined that gemcitabine could be safely combined with radiotherapy directed to the gross disease without inclusion of clinically negative lymph node-bearing areas.

Preclinical studies using pancreatic cancer cells have found that gemcitabine is a marked ADS PTV-331-EF sensitizer, even at noncytotoxic concentrations [7]and that the addition of sorafenib to radiotherapy could enhance tumor growth delay [8]. These findings suggest that the combination of all three agents, gemcitabine, sorafenib, and radiotherapy, could result in improved control of both local and distant sites. The present Phase I study was performed to evaluate the safety profile and to determine the recommended dose of sorafenib in combination with gemcitabine and concomitant radiation therapy. Patients and Methods The protocol for this trial and supporting CONSORT checklist are available as supporting information in Checklist S1 Annex 1 and Protocol S1 Annex 2 Patients with histologically or cytologically proven diagnosis of pancreatic adenocarcinoma were included in the study if they presented a locally advanced disease judged unresectable by radiological criteria: Pretreatment evaluation comprised symptom assessment, physical examination, hematology, ADS PTV-331-EF biochemistry, CA The planned treatment duration was 5 weeks, and consisted of: Sorafenib was temporally discontinued when radiotherapy was delayed for more than 3 days.

Maintenance with sorafenib was allowed in the absence of tumor progression after chemoradiation.

Telomeric DNA dimerizes by formation of guanine tetrads between hairpin loops Nature

Patients were monitored weekly, including hematology, serum chemistries, and toxicity assessment. Dimakov, Comparison ADS PTV-331-EF of analog and digital correction of a primary mirror aberration in observing telescopes, in Laser Optics Duban, G.

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