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Báo cáo khoa học: " Gastrointestinal toxicity of vorinostat: reanalysis of phase 1 study results with emphasis on dosevolume effects of pelvic radiotherapy"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Radiation Oncology cung cấp cho các bạn kiến thức về ngành y đề tài: Gastrointestinal toxicity of vorinostat: reanalysis of phase 1 study results with emphasis on dosevolume effects of pelvic radiotherapy. | Bratland et al. Radiation Oncology 2011 6 33 http www.ro-journal.eom content 6 1 33 RADIATION ONCOLOGY SHORT REPORT Open Access Gastrointestinal toxicity of vorinostat reanalysis of phase 1 study results with emphasis on dosevolume effects of pelvic radiotherapy Ase Bratland1 Svein Dueland1 Donal Hollywood4 Kjersti Flatmark2 3 and Anne H Ree5 6 Abstract Background In early-phase studies with targeted therapeutics and radiotherapy it may be difficult to decide whether an adverse event should be considered a dose-limiting toxicity DLT of the investigational systemic agent as acute normal tissue toxicity is frequently encountered with radiation alone. We have reanalyzed the toxicity data from a recently conducted phase 1 study on vorinostat a histone deacetylase inhibitor in combination with pelvic palliative radiotherapy with emphasis on the dose distribution within the irradiated bowel volume to the development of DLT. Findings Of 14 eligible patients three individuals experienced Common Terminology Criteria of Adverse Events grade 3 gastrointestinal and related toxicities representing a toxicity profile vorinostat has in common with radiotherapy to pelvic target volumes. For each study patient the relative volumes of small bowel receiving radiation doses between 6 Gy and 30 Gy at 6-Gy intervals V6-V30 were determined from the treatment-planning computed tomography scans. The single patient that experienced a DLT at the second highest dose level of vorinostat which was determined as the maximum-tolerated dose had V6-V30 dose-volume estimates that were considerably higher than any other study patient. This patient may have experienced an adverse radiation dosevolume effect rather than a toxic effect of the investigational drug. Conclusions When reporting early-phase trial results on the tolerability of a systemic targeted therapeutic used as potential radiosensitizing agent radiation dose-volume effects should be quantified to enable full interpretation of the study