1. Phase I trial of the combination of the Akt inhibitor nelfinavir and chemoradiation for locally advanced rectal cancer
- Author
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Buijsen, J., Buijsen, J., Lammering, G., Jansen, R.L., Beets, G.L., Wals, J., Sosef, M., Den Boer, M.O., Leijtens, J., Riedl, R.G., Theys, J., Lambin, P., Buijsen, J., Buijsen, J., Lammering, G., Jansen, R.L., Beets, G.L., Wals, J., Sosef, M., Den Boer, M.O., Leijtens, J., Riedl, R.G., Theys, J., and Lambin, P.
- Abstract
PURPOSE: To investigate the toxicity of nelfinavir, administered during preoperative chemoradiotherapy (CRT) in patients with locally advanced cancer. MATERIAL AND METHODS: Twelve patients were treated with to 50.4Gy combined with capecitabine 825mg/m2 BID. Three dose levels nelfinavir were tested: 750mg BID (DL1), 1250mg BID (DL2) and an level of 1000mg BID (DL3). Surgery was performed between 8 and 10weeks completion of CRT. Primary endpoint was dose-limiting toxicity (DLT), any grade 3 or higher non-hematological or grade 4 or higher toxicity. RESULTS: Eleven patients could be analyzed: 5 were treated in DL2 and 3 in DL3. The first 3 patients in DL1 did not develop a DLT. In patient developed gr 3 diarrhea, 1 patient had gr 3 transaminase patient had a gr 3 cholangitis with unknown cause. An intermediate dose tested in DL3. In this group 2 patients developed gr 3 diarrhea and 1 3 transaminase elevation and gr 4 post-operative wound complication. patients achieved a pathological complete response (pCR). CONCLUSIONS: 750mg BID was defined as the recommended phase II dose in combination capecitabine and 50.4Gy pre-operative radiotherapy in rectal cancer. response evaluations are promising, but a further phase II study is more information about efficacy of this treatment regimen.
- Published
- 2013