Journal article
Phase 1 trial of nelfinavir added to standard cisplatin chemotherapy with concurrent pelvic radiation for locally advanced cervical cancer
Cancer, v 127(13), pp 2279-2293
01 Jul 2021
PMID: 33932031
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Nelfinavir (NFV), an HIV-1 protease inhibitor, has been shown to sensitize cancer cells to chemoradiation (CRT). The objectives of this phase 1 trial were to evaluate safety and identify the recommended phase 2 dose of NFV added to concurrent CRT for locally advanced cervical cancer.
Two dose levels of NFV were evaluated: 875 mg orally twice daily (dose level 1 [DL1]) and 1250 mg twice daily (DL2). NFV was initiated 7 days before CRT and continued through CRT completion. Toxicity, radiographic responses, and pathologic responses were evaluated. Serial tumor biopsies (baseline, after NFV monotherapy, on NFV + CRT, and posttreatment) were evaluated by immunohistochemistry, NanoString, and reverse-phase-protein-array analyses.
NFV sensitized cervical cancer cells to radiation, increasing apoptosis and tumor suppression in vivo. Patients (n = 13) with International Federation of Gynecology and Obstetrics stage IIA through IVA squamous cell cervical carcinoma were enrolled, including 7 patients at DL1 and 6 patients at DL2. At DL1, expansion to 6 patients was required after a patient developed a dose-limiting toxicity, whereas no dose-limiting toxicities occurred at DL2. Therefore, DL2 was established as the recommended phase 2 dose. All patients at DL2 completed CRT, and 1 of 6 experienced grade 3 or 4 anemia, nausea, and diarrhea. One recurrence was noted at DL2, with disease outside the radiation field. Ten of 11 evaluable patients remained without evidence of disease at a median follow-up of 50 months. NFV significantly decreased phosphorylated Akt levels in tumors. Cell cycle and cancer pathways also were reduced by NFV and CRT.
NFV with CRT is well tolerated. The response rate is promising compared with historic controls in this patient population and warrants further investigation.
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Details
- Title
- Phase 1 trial of nelfinavir added to standard cisplatin chemotherapy with concurrent pelvic radiation for locally advanced cervical cancer
- Creators
- Arlene E Garcia-Soto - Sylvester Comprehensive Cancer CenterNathalie D McKenzie - Sylvester Comprehensive Cancer CenterMargaret E Whicker - University of PennsylvaniaJoseph M Pearson - Sylvester Comprehensive Cancer CenterEdward A Jimenez - Sylvester Comprehensive Cancer CenterLorraine Portelance - Sylvester Comprehensive Cancer CenterJennifer J Hu - Sylvester Comprehensive Cancer CenterJoseph A Lucci, 3rd - The University of Texas Health Science Center at HoustonRehman Qureshi - The Wistar InstituteAndrew Kossenkov - The Wistar InstituteLauren Schwartz - University of PennsylvaniaGordon B Mills - Oregon Health & Science UniversityAmit Maity - University of PennsylvaniaLilie L Lin - The University of Texas Health Science Center at HoustonFiona Simpkins - University of Pennsylvania
- Publication Details
- Cancer, v 127(13), pp 2279-2293
- Publisher
- Wiley
- Grant note
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation R01 CA174976 / NCI NIH HHS P30 CA010815 / NCI NIH HHS R50 CA211199 / NCI NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems; Drexel University
- Web of Science ID
- WOS:000646107600001
- Scopus ID
- 2-s2.0-85105171446
- Other Identifier
- 991019350297104721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Oncology