A Dose Escalation and Pharmacodynamic Study of Triapine and Radiation in Patients With Locally Advanced Pancreas Cancer
- Department of Internal Medicine, Ohio State University, Columbus, Ohio (United States)
- Department of Radiation Oncology, Ohio State University, Columbus, Ohio (United States)
- Department of Radiology, Ohio State University, Columbus, Ohio (United States)
- Center for Biostatistics, Ohio State University, Columbus, Ohio (United States)
- Ohio State University Comprehensive Cancer Center, Columbus, Ohio (United States)
- City of Hope Comprehensive Cancer Center, Duarte, California (United States)
- Department of Surgery, Division of Surgical Oncology, Ohio State University, Columbus, Ohio (United States)
- Cancer Therapeutics Evaluation Program, National Cancer Institute, Rockville, Maryland (United States)
Purpose: Triapine, a novel inhibitor of the M2 subunit of ribonucleotide reductase (RR), is a potent radiosensitizer. This phase 1 study, sponsored by the National Cancer Institute Cancer Therapy Evaluation Program, assessed the safety and tolerability of triapine in combination with radiation (RT) in patients with locally advanced pancreas cancer (LAPCA). Methods and Materials: We evaluated 3 dosage levels of triapine (24 mg/m{sup 2}, 48 mg/m{sup 2}, 72 mg/m{sup 2}) administered with 50.4 Gy of RT in 28 fractions. Patients with LAPCA received triapine thrice weekly, every other week during the course of RT. Dose-limiting toxicity (DLT) was assessed during RT and for 4 weeks after its completion. Dynamic contrast-enhanced magnetic resonance imaging and serum RR levels were evaluated as potential predictors for early response. Results: Twelve patients were treated. Four patients (1 nonevaluable) were enrolled at dosage level 1 (DL1), 3 patients at DL2, and 5 patients (2 nonevaluable) at DL3. No DLTs were observed, and the maximum tolerated dose was not reached. Two patients (17%) achieved partial response, and 6 patients (50%) had stable disease. One patient underwent R0 resection after therapy. Ninety-two percent of patients (100% at DL3) experienced freedom from local tumor progression. In 75% of patients who eventually experienced progression, metastases developed without local progression. RR levels did not seem to predict outcome. In 4 patients with available data, dynamic contrast-enhanced magnetic resonance imaging may predict early response or resistance to therapy. Conclusion: The combination of triapine at 72 mg/m{sup 2} 3 times weekly every other week and standard RT is tolerable with interesting activity in patients with LAPCA.
- OSTI ID:
- 22149634
- Journal Information:
- International Journal of Radiation Oncology, Biology and Physics, Vol. 84, Issue 4; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0360-3016
- Country of Publication:
- United States
- Language:
- English
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