Show simple item record

dc.contributor.authorBratland, Ase
dc.contributor.authorDueland, Svein
dc.contributor.authorHollywood, Donal
dc.contributor.authorFlatmark, Kjersti
dc.contributor.authorRee, Anne H
dc.date.accessioned2011-05-04T07:42:35Z
dc.date.available2011-05-04T07:42:35Z
dc.date.issued2011-04-08
dc.identifierhttp://dx.doi.org/10.1186/1748-717X-6-33
dc.identifier.citationRadiation Oncology. 2011 Apr 08;6(1):33
dc.identifier.urihttp://hdl.handle.net/10147/129049
dc.description.abstractAbstract 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 dose-volume 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 toxicity profile. Trial registration ClinicalTrials.gov: NCT00455351
dc.titleGastrointestinal toxicity of vorinostat: reanalysis of phase 1 study results with emphasis on dose-volume effects of pelvic radiotherapy
dc.typeJournal Article
dc.language.rfc3066en
dc.rights.holderBratland et al.; licensee BioMed Central Ltd.
dc.description.statusPeer Reviewed
dc.date.updated2011-05-04T05:00:59Z
refterms.dateFOA2018-08-22T12:14:23Z
html.description.abstractAbstract 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 dose-volume 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 toxicity profile. Trial registration ClinicalTrials.gov: NCT00455351


Files in this item

Thumbnail
Name:
1748-717X-6-33.xml
Size:
35.15Kb
Format:
XML
Thumbnail
Name:
1748-717X-6-33.pdf
Size:
181.2Kb
Format:
PDF

This item appears in the following Collection(s)

Show simple item record