Pharmacodynamic and therapeutic pilot studies of single-agent ribavirin in patients with human papillomavirus–related malignancies Journal Article

   

Authors:	Burman, B.; Drutman, S. B.; Fury, M. G.; Wong, R. J.; Katabi, N.; Ho, A. L.; Pfister, D. G.
Article Title:	Pharmacodynamic and therapeutic pilot studies of single-agent ribavirin in patients with human papillomavirus–related malignancies
Abstract:	Objectives: Ribavirin inhibits eukaryotic translation initiation factor 4E (eIF4E), thereby decreasing cap-dependent translation. In this two-part study, we assessed the pharmacodynamic effects and therapeutic potential of ribavirin in human papillomavirus (HPV)–related malignancies. Methods: In the pharmacodynamic study, ribavirin (400 mg BID for 14 days) was evaluated in 8 patients with HPV-positive localized oropharyngeal carcinoma with phosphorylated-eIF4E (p-eIF4E) ≥ 30%. In the therapeutic study, ribavirin (1400 mg BID in 28-day cycles, continuously dosed) was evaluated in 12 patients with recurrent and/or metastatic HPV-related cancer. Dose interruptions or reductions were allowed according to prespecified criteria. Toxicities were assessed in accordance with National Cancer Institute Common Terminology Criteria for Adverse Events version 4; response was assessed using Response Evaluation Criteria in Solid Tumors version 1.1. Patients remained on study until disease progression or unacceptable toxicity. Results: Six patients were evaluable in the pharmacodynamic study: 4 had decreased p-eIF4E after 14 days of ribavirin. In the therapeutic study, 12 patients were evaluable for toxicity, and 9 were evaluable for response. Among these, median follow-up was 3.5 months, and best overall response was stable disease in 5 patients and progression of disease in 4 patients. Median progression-free survival was 1.8 months. The most common treatment-related adverse events (grade > 2) were anemia, dyspnea, and hyperbilirubinemia. All patients had anemia (grades 1–3), with 33% having at least 1 dose reduction. Conclusion: Oral ribavirin decreases p-eIF4E levels and is well-tolerated. However, a clear signal of efficacy in patients with recurrent and/or metastatic HPV-related cancers was not observed. (NCT02308241, NCT01268579) © 2022
Keywords:	ribavirin; human papillomavirus; eif4e; cap-dependent translation; hpv-related cancers
Journal Title:	Oral Oncology
Volume:	128
ISSN:	1368-8375
Publisher:	Elsevier Inc.
Date Published:	2022-05-01
Start Page:	105806
Language:	English
DOI:	10.1016/j.oraloncology.2022.105806
PROVIDER:	scopus
PUBMED:	35339025
PMCID:	PMC9788648
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85126954269&doi=10.1016%2fj.oraloncology.2022.105806&partnerID=40&md5=49a757125efaeaee7130200af3e26df3
Notes:	Article -- Export Date: 2 May 2022 -- Source: Scopus

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