(P001) Triapine Radiochemotherapy Improves Survival in Women With Stage IIIb Cervical Cancer

Charles A. Kunos, MD, PhD, Tracy Sherertz, MD; Case Western Reserve University; Summa Health System; University Hospitals of Cleveland

Purpose: The Surveillance, Epidemiology and End Results (SEER) registry has published a 3-year cancer-related survival rate of 55% among the 2,236 cases of stage IIIB squamous cell cervical cancer between 1988 and 2001. Triapine irreversibly blocks ribonucleotide reductase, the de novo rate-limiting generator of DNA building blocks, and enhances cytotoxic effects of cisplatin chemotherapy and radiation therapy. Whether triapine radiochemotherapy reduces extrapelvic disease progression and disease-related death is not known.

Materials and Methods: Between 2006 and 2011, 12 women with clinical stage IIIB cervical cancer underwent three-times-weekly intravenous triapine (25 mg/m²), once-weekly cisplatin (40 mg/m²), and daily pelvic irradiation (45 Gy) followed by brachytherapy (30–40 Gy) on phase I and phase II trials. Lymph node positivity was determined by CT and positron emission tomography (PET) with [18F]-fluoro-2-deoxy-D-glucose (FDG). Cancer-related survival was evaluated by the Kaplan-Meier method.

Results: Median follow-up was 30 months (range: 4–90 mo). Pretherapy FDG-PET/CT detected abnormal FDG uptake in pelvic lymph nodes in 9 (75%) of the 12 stage IIIB women. One local (8 mo) and three distant (5, 23, and 24 mo) relapses have occurred after triapine radiochemotherapy. Two (17%) cervical cancer-related deaths and two (17%) non–cancer-related deaths have been observed. The 3-year cancer-related survival rate for women with stage IIIB cervical cancer was 74% (95% confidence interval [CI], 58%–90%), which compares favorably with a 55% SEER control.

Conclusions: Findings suggest that triapine radiochemotherapy provides improved cancer-related survival in women with stage IIIB cervical cancer. A prospective National Cancer Institute–sponsored (NCT01835171) randomized phase II trial of triapine radiochemotherapy vs radiochemotherapy has begun accrual nationwide.