Phase I trial of the combination of the Akt inhibitor nelfinavir and chemoradiation for locally advanced rectal cancer

J. Buijsen*, G. Lammering, R.L. Jansen, G.L. Beets, J. Wals, M. Sosef, M.O. Den Boer, J. Leijtens, R.G. Riedl, J. Theys, P. Lambin

*Corresponding author for this work

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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.
Original languageEnglish
Pages (from-to)184-188
Number of pages5
JournalRadiotherapy and Oncology
Volume107
Issue number2
DOIs
Publication statusPublished - May 2013

Keywords

  • Rectal cancer
  • Chemoradiation
  • Phase I
  • Nelfinavir
  • HIV PROTEASE INHIBITOR
  • PREOPERATIVE RADIATION
  • COLORECTAL-CANCER
  • MANAGEMENT
  • MUTATIONS
  • PATHWAY
  • CELLS
  • VIVO
  • CHEMORADIOTHERAPY
  • INDINAVIR

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