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Hill, E.J.* ; Roberts, C.* ; Franklin, J.M.* ; Enescu, M.* ; West, N.X.* ; MacGregor, T.P.* ; Chu, K.Y.K.* ; Boyle, L.* ; Blesing, C.* ; Wang, L.M.* ; Mukherjee, S.* ; Anderson, E.M.* ; Brown, G.D.* ; Dutton, S.* ; Love, S.B.* ; Schnabel, J.A.* ; Quirke, P.* ; Muschel, R.J.* ; McKenna, W.G.* ; Partridge, M.* ; Sharma, R.A.*

Clinical trial of oral nelfinavir before and during radiation therapy for advanced rectal cancer.

Clin. Cancer Res. 22, 1922-1931 (2016)
Verlagsversion DOI PMC
Free by publisher
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Purpose: Nelfinavir, a PI3K pathway inhibitor, is a radiosensitizer that increases tumor blood flow in preclinical models. We conducted an early-phase study to demonstrate the safety of nelfinavir combined with hypofractionated radiotherapy (RT) and to develop biomarkers of tumor perfusion and radiosensitization for this combinatorial approach. Experimental Design: Ten patients with T3-4 N0-2 M1 rectal cancer received 7 days of oral nelfinavir (1,250 mg b.i.d.) and a further 7 days of nelfinavir during pelvic RT (25 Gy/5 fractions/7 days). Perfusion CT (p-CT) and DCE-MRI scans were performed pretreatment, after 7 days of nelfinavir and prior to the last fraction of RT. Biopsies taken pretreatment and 7 days after the last fraction of RT were analyzed for tumor cell density (TCD). Results: There were 3 drug-related grade 3 adverse events: diarrhea, rash, and lymphopenia. On DCE-MRI, there was a mean 42% increase in median Ktrans, and a corresponding median 30% increase in mean blood flow on p-CT during RT in combination with nelfinavir. Median TCD decreased from 24.3% at baseline to 9.2% in biopsies taken 7 days after RT (P = 0.01). Overall, 5 of 9 evaluable patients exhibited good tumor regression on MRI assessed by tumor regression grade (mrTRG). Conclusions: This is the first study to evaluate nelfinavir in combination with RT without concurrent chemotherapy. It has shown that nelfinavir-RT is well tolerated and is associated with increased blood flow to rectal tumors. The efficacy of nelfinavir-RT versus RT alone merits clinical evaluation, including measurement of tumor blood flow.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
ISSN (print) / ISBN 1078-0432
e-ISSN 1557-3265
Zeitschrift Clinical Cancer Research
Quellenangaben Band: 22, Heft: 8, Seiten: 1922-1931 Artikelnummer: , Supplement: ,
Verlag American Association for Cancer Research (AACR)
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute for Machine Learning in Biomed Imaging (IML)