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

Publication ,  Journal Article
Blumenthal, GM; Gills, JJ; Ballas, MS; Bernstein, WB; Komiya, T; Dechowdhury, R; Morrow, B; Root, H; Chun, G; Helsabeck, C; Steinberg, SM ...
Published in: Oncotarget
September 30, 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.

Duke Scholars

Published In

Oncotarget

DOI

EISSN

1949-2553

Publication Date

September 30, 2014

Volume

5

Issue

18

Start / End Page

8161 / 8172

Location

United States

Related Subject Headings

  • Young Adult
  • Treatment Outcome
  • Tomography, X-Ray Computed
  • Time Factors
  • Neoplasms
  • Nelfinavir
  • Middle Aged
  • Maximum Tolerated Dose
  • Maryland
  • Male
 

Citation

APA
Chicago
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Blumenthal, G. M., Gills, J. J., Ballas, M. S., Bernstein, W. B., Komiya, T., Dechowdhury, R., … Dennis, P. A. (2014). A phase I trial of the HIV protease inhibitor nelfinavir in adults with solid tumors. Oncotarget, 5(18), 8161–8172. https://doi.org/10.18632/oncotarget.2415
Blumenthal, Gideon M., Joell J. Gills, Marc S. Ballas, Wendy B. Bernstein, Takefumi Komiya, Roopa Dechowdhury, Betsy Morrow, et al. “A phase I trial of the HIV protease inhibitor nelfinavir in adults with solid tumors.Oncotarget 5, no. 18 (September 30, 2014): 8161–72. https://doi.org/10.18632/oncotarget.2415.
Blumenthal GM, Gills JJ, Ballas MS, Bernstein WB, Komiya T, Dechowdhury R, et al. A phase I trial of the HIV protease inhibitor nelfinavir in adults with solid tumors. Oncotarget. 2014 Sep 30;5(18):8161–72.
Blumenthal, Gideon M., et al. “A phase I trial of the HIV protease inhibitor nelfinavir in adults with solid tumors.Oncotarget, vol. 5, no. 18, Sept. 2014, pp. 8161–72. Pubmed, doi:10.18632/oncotarget.2415.
Blumenthal GM, Gills JJ, Ballas MS, Bernstein WB, Komiya T, Dechowdhury R, Morrow B, Root H, Chun G, Helsabeck C, Steinberg SM, LoPiccolo J, Kawabata S, Gardner ER, Figg WD, Dennis PA. A phase I trial of the HIV protease inhibitor nelfinavir in adults with solid tumors. Oncotarget. 2014 Sep 30;5(18):8161–8172.

Published In

Oncotarget

DOI

EISSN

1949-2553

Publication Date

September 30, 2014

Volume

5

Issue

18

Start / End Page

8161 / 8172

Location

United States

Related Subject Headings

  • Young Adult
  • Treatment Outcome
  • Tomography, X-Ray Computed
  • Time Factors
  • Neoplasms
  • Nelfinavir
  • Middle Aged
  • Maximum Tolerated Dose
  • Maryland
  • Male