Clinical Research Papers:

A phase I trial of the HIV protease inhibitor nelfinavir in adults with solid tumors

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 and Phillip A. Dennis

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Oncotarget. 2014; 5:8161-8172. https://doi.org/10.18632/oncotarget.2415

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Gideon M. Blumenthal1, Joell J. Gills3, Marc S. Ballas1, Wendy B. Bernstein1, Takefumi Komiya1, Roopa Dechowdhury1, Betsy Morrow1, Hyejeong Root1, Guinevere Chun1, Cynthia Helsabeck1, Seth M. Steinberg2, Jaclyn LoPiccolo1, Shigeru Kawabata3, Erin R. Gardner1, William D. Figg1, Phillip A. Dennis3

1 Medical Oncology Branch, National Cancer Institute, Bethesda, MD

2 Biostatistics and Data Management Section, National Cancer Institute, Bethesda, MD

3 Department of Oncology, Johns Hopkins School of Medicine, Baltimore, MD, USA

Correspondence to:

Phillip A. Dennis, e-mail: [email protected]

Key words: Nelfinavir, phase I clinical trial, AKT, endoplasmic reticulum stress, neuroendocrine

Received: June 30, 2014     Accepted: August 28, 2014     Published: September 05, 2014


Nelfinavir is an HIV protease inhibitor being repurposed as an anti-cancer agent in preclinical models and in small oncology trials, yet the MTD of nelfinavir has not been determined. Therefore, we conducted a Phase Ia study to establish the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of nelfinavir in subjects with advanced solid tumors. Adults with refractory cancers were given oral nelfinavir twice daily with pharmacokinetic and pharmacodynamic analyses. Twenty-eight subjects were enrolled. Nelfinavir was generally well tolerated. Common adverse events included diarrhea, anemia, and lymphopenia, which were mostly mild. The DLT was rapid-onset neutropenia that was reversible. The MTD was established at 3125 mg twice daily. In an expansion cohort at the MTD, one of 11 (9%) evaluable subjects had a confirmed partial response. This, plus two minor responses, occurred in subjects with neuroendocrine tumors of the midgut or pancreatic origin. Thirty-six percent of subjects had stable disease for more than 6 months. In peripheral blood mononuclear cells, Nelfinavir inhibited AKT and induced markers of ER stress. In summary, nelfinavir is well tolerated in cancer patients at doses 2.5 times the FDA-approved dose for HIV management and showed preliminary activity in tumors of neuroendocrine origin.

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