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Long-Term Disease Control with Triapine-Based Radiochemotherapy for Patients with Stage IB2-IIIB Cervical Cancer.

AbstractBACKGROUND:
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/m(2)), once-weekly cisplatin (40 mg/m(2)), 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.
AuthorsCharles A Kunos, Tracy M Sherertz
JournalFrontiers in oncology (Front Oncol) Vol. 4 Pg. 184 ( 2014) ISSN: 2234-943X [Electronic] Switzerland
PMID25105092 (Publication Type: Journal Article)

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