Triapine® is a small molecule chelator that blocks a critical step in DNA synthesis by inhibiting ribonuclease reductase, an enzyme responsible for the replication of tumor cells. Inhibition of this enzyme has been shown in vitro and in vivo to enhance the anti-tumor activity of several standard anticancer agents and enhance tumor sensitivity to radiation treatment. DNA synthesis disruption is due in part to the effective ability of Triapine® to chelate iron intracellularly. Some tumors have been shown to be sensitive to iron chelator therapy which provides a useful target for anti-cancer drugs and results in tumor cell death.
Triapine® is being developed under a Clinical Trials Agreement between the National Cancer Institute and Nanotherapeutics for the treatment of non-localized cervical cancer. Thus far, Triapine® has proven to be effective in two small clinical studies. The first study recruited 10 patients with stage IB2 to IVB cervical cancer who were treated with Triapine® combined with cisplatin and daily pelvic radiation; all 10 patients had a complete clinical response with a median of 18 months of follow-up (range: 6-32 months)(1). In a second phase 2 study using the same therapeutic regimen in 25 patients with advanced cervical (N = 22) or vaginal (N = 3) cancers, clinical response was achieved in 24 of the 25 patients (median follow-up of 20 months (range: 2-35 months). Follow-up of the patients who participated in these trials is continuing.
Currently, Triapine® is being studied in a Phase 2 randomized trial with cisplatin/radiation vs cisplatin/radiation alone for women diagnosed with IB-IVA cervical cancer and stage II-IVA vaginal cancer. Primary endpoint is the 3 month post therapy F-FDG PET/CT response and targeted recruitment is 73 subjects. This study is actively recruiting (ClinicalTrials.gov Identifier: NCT01835171).
Nanotherapeutics is pleased to collaborate with National Cancer Institute to advance Triapine® for cervical and vaginal cancer treatment.
Kunos CA, Radivoyevitch T, Pink J, et al. Ribonucleotide reductase inhibition enhances chemoradiosensitivity of human cervical cancers. Radiat Res 2010; 174:574-581.
Kunos CA, Radivoyevitch T, Waggoner S. et al. Radiochemotherapy plus 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, NSC #663249) in advanced-stage cervical and vaginal cancers. Gynecol Oncol 2013; 130:75-80.
Rose, PG, Bundy, BN, Watkins, EB, et al. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. New England Journal of Medicine 1999; 340:1144-53.