PURPOSE: To investigate the toxicity of nelfinavir, administered during preoperative chemoradiotherapy (CRT) in patients with locally advanced rectal cancer. MATERIAL AND METHODS: Twelve patients were treated with chemoradiotherapy to 50.4 Gy combined with capecitabine 825 mg/m(2) BID. Three dose levels (DL) of nelfinavir were tested: 750 mg BID (DL1), 1250 mg BID (DL2) and an intermediate level of 1000 mg BID (DL3). Surgery was performed between 8 and 10 weeks after completion of CRT. Primary endpoint was dose-limiting toxicity (DLT), defined as any grade 3 or higher non-hematological or grade 4 or higher hematological toxicity. RESULTS: Eleven patients could be analyzed: 5 were treated in DL1, 3 in DL2 and 3 in DL3. The first 3 patients in DL1 did not develop a DLT. In DL2 one patient developed gr 3 diarrhea, 1 patient had gr 3 transaminase elevation and 1 patient had a gr 3 cholangitis with unknown cause. An intermediate dose level was tested in DL3. In this group 2 patients developed gr 3 diarrhea and 1 patient gr 3 transaminase elevation and gr 4 post-operative wound complication. Three patients achieved a pathological complete response (pCR). CONCLUSIONS: Nelfinavir 750 mg BID was defined as the recommended phase II dose in combination with capecitabine and 50.4 Gy pre-operative radiotherapy in rectal cancer. First tumor response evaluations are promising, but a further phase II study is needed to get more information about efficacy of this treatment regimen.
PURPOSE: To investigate the toxicity of nelfinavir, administered during preoperative chemoradiotherapy (CRT) in patients with locally advanced rectal cancer. MATERIAL AND METHODS: Twelve patients were treated with chemoradiotherapy to 50.4 Gy combined with capecitabine 825 mg/m(2) BID. Three dose levels (DL) of nelfinavir were tested: 750 mg BID (DL1), 1250 mg BID (DL2) and an intermediate level of 1000 mg BID (DL3). Surgery was performed between 8 and 10 weeks after completion of CRT. Primary endpoint was dose-limiting toxicity (DLT), defined as any grade 3 or higher non-hematological or grade 4 or higher hematological toxicity. RESULTS: Eleven patients could be analyzed: 5 were treated in DL1, 3 in DL2 and 3 in DL3. The first 3 patients in DL1 did not develop a DLT. In DL2 one patient developed gr 3 diarrhea, 1 patient had gr 3 transaminase elevation and 1 patient had a gr 3 cholangitis with unknown cause. An intermediate dose level was tested in DL3. In this group 2 patients developed gr 3 diarrhea and 1 patient gr 3 transaminase elevation and gr 4 post-operative wound complication. Three patients achieved a pathological complete response (pCR). CONCLUSIONS:Nelfinavir 750 mg BID was defined as the recommended phase II dose in combination with capecitabine and 50.4 Gy pre-operative radiotherapy in rectal cancer. First tumor response evaluations are promising, but a further phase II study is needed to get more information about efficacy of this treatment regimen.
Authors: Esme J Hill; Corran Roberts; Jamie M Franklin; Monica Enescu; Nicholas West; Thomas P MacGregor; Kwun-Ye Chu; Lucy Boyle; Claire Blesing; Lai-Mun Wang; Somnath Mukherjee; Ewan M Anderson; Gina Brown; Susan Dutton; Sharon B Love; Julia A Schnabel; Phil Quirke; Ruth Muschel; William G McKenna; Michael Partridge; Ricky A Sharma Journal: Clin Cancer Res Date: 2016-02-09 Impact factor: 12.531
Authors: Arlene E Garcia-Soto; Nathalie D McKenzie; Margaret E Whicker; Joseph M Pearson; Edward A Jimenez; Lorraine Portelance; Jennifer J Hu; Joseph A Lucci; Rehman Qureshi; Andrew Kossenkov; Lauren Schwartz; Gordon B Mills; Amit Maity; Lilie L Lin; Fiona Simpkins Journal: Cancer Date: 2021-05-01 Impact factor: 6.860
Authors: Gideon M Blumenthal; Joell J Gills; Marc S Ballas; Wendy B Bernstein; Takefumi Komiya; Roopa Dechowdhury; Betsy Morrow; Hyejeong Root; Guinevere Chun; Cynthia Helsabeck; Seth M Steinberg; Jaclyn LoPiccolo; Shigeru Kawabata; Erin R Gardner; William D Figg; Phillip A Dennis Journal: Oncotarget Date: 2014-09-30
Authors: Charlotte E Johnson; David K Hunt; Marie Wiltshire; Terry P Herbert; Julian R Sampson; Rachel J Errington; D Mark Davies; Andrew R Tee Journal: Mol Oncol Date: 2014-11-22 Impact factor: 6.603