Hill, EJ, Roberts, C, Franklin, JM et al. (18 more authors) (2016) Clinical Trial of Oral Nelfinavir Before and During Radiation Therapy for Advanced Rectal Cancer. Clinical Cancer Research, 22 (8). pp. 1922-1931. ISSN 1078-0432
Abstract
Purpose: Nelfinavir, a PI3-kinase pathway inhibitor, is a radiosensitizer which 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. Patients and Methods: Ten patients with T3-4 N0-2 M1 rectal cancer received 7 days of oral nelfinavir (1250 mg bd) 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 pre-treatment, after 7 days of nelfinavir and prior to last fraction of RT. Biopsies taken pre-treatment and 7 days after the last fraction of RT were analysed for tumor cell density (TCD). Results: There were 3 drug-related grade 3 adverse events: diarrhea, rash, 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, 5/9 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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2016, American Association for Cancer Research. This is an author produced version of a paper published in Clinical Cancer Research. Uploaded in accordance with the publisher's self-archiving policy. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 22 Jan 2016 16:45 |
Last Modified: | 14 Apr 2017 04:06 |
Published Version: | http://dx.doi.org/10.1158/1078-0432.CCR-15-1489 |
Status: | Published |
Publisher: | American Association for Cancer Research |
Identification Number: | 10.1158/1078-0432.CCR-15-1489 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:94074 |