AUTHOR=Kunos Charles A. , Sherertz Tracy M.
TITLE=Long-Term Disease Control with Triapine-Based Radiochemotherapy for Patients with Stage IB2–IIIB Cervical Cancer
JOURNAL=Frontiers in Oncology
VOLUME=4
YEAR=2014
URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2014.00184
DOI=10.3389/fonc.2014.00184
ISSN=2234-943X
ABSTRACT=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 advanced-stage cervical cancer. Triapine inhibits ribonucleotide reductase, the rate-limiting enzyme responsible for DNA-building 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 (40 mg/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 advanced-stage cervical cancer, worthy of randomized clinical trial study.