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

Autor: Jaap Wals, Geerard L. Beets, Philippe Lambin, Marien O Den Boer, Guido Lammering, Jeroen W. A. Leijtens, Jeroen Buijsen, Meindert N. Sosef, Rob L. H. Jansen, Robert G. Riedl, Jan Theys
Přispěvatelé: RS: NUTRIM - R2 - Gut-liver homeostasis, Interne Geneeskunde, Pathologie, RS: GROW - School for Oncology and Reproduction, Radiotherapie, Surgery
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Male
Colorectal cancer
medicine.medical_treatment
Phases of clinical research
Gastroenterology
COLORECTAL-CANCER
VIVO
PATHWAY
0302 clinical medicine
Clinical endpoint
Rectal cancer
0303 health sciences
Nelfinavir
Hematology
Chemoradiotherapy
Middle Aged
Combined Modality Therapy
3. Good health
medicine.anatomical_structure
Chemoradiation
Oncology
030220 oncology & carcinogenesis
Female
medicine.drug
medicine.medical_specialty
Rectum
Capecitabine
03 medical and health sciences
Phase I
Internal medicine
MANAGEMENT
medicine
Humans
Radiology
Nuclear Medicine and imaging
HIV PROTEASE INHIBITOR
030304 developmental biology
Aged
Dose-Response Relationship
Drug
MUTATIONS
business.industry
Rectal Neoplasms
medicine.disease
INDINAVIR
Surgery
Radiation therapy
PREOPERATIVE RADIATION
CELLS
business
Proto-Oncogene Proteins c-akt
Zdroj: Radiotherapy and Oncology
Radiotherapy and Oncology; Vol 107
Radiotherapy and Oncology, 107(2), 184-188. Elsevier Ireland Ltd
ISSN: 0167-8140
DOI: 10.1016/j.radonc.2013.03.023
Popis: 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/m2 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.
Databáze: OpenAIRE
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