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Open Access Publications from the University of California

Long-term disease control with triapine-based radiochemotherapy for patients with stage IB2-IIIB cervical cancer

  • Author(s): Kunos, CA
  • Sherertz, TM
  • et al.

Background: National Cancer Institute phase I #7336 and phase II #8327 clinical trials explored the safety and efficacy of triapine (NSC #663249) added to cisplatin radiochemotherapy in untreated patients with advancedstage cervical cancer. Triapine inhibits ribonucleotide reductase, the rate-limiting enzyme responsible for DNAbuilding deoxyribonucleotides, and thereby, enhances radiochemosensitivity by prolonging DNA repair time. Here we report 3-year efficacy endpoints of pelvic locoregional relapse rate, disease-free and overall survivals. Methods: Eligible patients with bulky IB-IIIB cervical cancer underwent three-times weekly triapine (25 or 50 mg/m2), once-weekly cisplatin (40mg/m2), and conventional daily pelvic radiation followed by brachytherapy. A cumulative incidence method estimated pelvic locoregional relapse rates. Disease-free survival was measured from radiochemotherapy start date to the date of first relapse or cancer-related death. Overall survival was measured from radiochemotherapy start date to the date of any-cause death. The Kaplan-Meier method estimated survivals. Findings: Between 2006 and 2011, 24 untreated patients with cervical cancer met criteria for reporting in this study. A median 3.4 years of follow-up time (range, 0.3-7.6 years) has been observed. All had squamous cancers and the majority had either node-positive stage IB-IIA (33%) or stage IIIB (42%) disease. The 3-year pelvic locoregional relapse rate, disease-free survival, and overall survival were 4% (95% confidence interval [CI], 0-20%), 80% (95% CI: 71-89%), and 82% (95% CI: 74%-90%), respectively. Interpretation: Triapine radiochemotherapy was safe, active, and effective in patients with untreated advancedstage cervical cancer, worthy of randomized clinical trial study. Funding: National Institutes of Health grants U01 CA62502 and P30 CA43703-17 © 2014 Kunos and Sherertz.

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