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Ref Type Journal Article
PMID (26861457)
Authors Hill EJ, Roberts C, Franklin JM, Enescu M, West N, MacGregor TP, Chu KY, Boyle L, Blesing C, Wang LM, Mukherjee S, Anderson EM, Brown G, Dutton S, Love SB, Schnabel JA, Quirke P, Muschel R, McKenna WG, Partridge M, Sharma RA
Title Clinical Trial of Oral Nelfinavir before and during Radiation Therapy for Advanced Rectal Cancer.
Journal Clinical cancer research : an official journal of the American Association for Cancer Research
Vol 22
Issue 8
Date 2016 Apr 15
URL
Abstract Text 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.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).There were 3 drug-related grade 3 adverse events: diarrhea, rash, and lymphopenia. On DCE-MRI, there was a mean 42% increase in medianKtrans, 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).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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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown rectum cancer not applicable Nelfinavir + Radiotherapy Phase I Actionable In a Phase I trial, the combination of Nelfinavir and radiotherapy resulted in median tumor cell density reduction from 24.3% at baseline to 9.2%, and tumor regression in 56% (5/9) of rectal cancer patients (PMID: 26861457). 26861457