This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Laurie, S. A. Articles by Lorence, R. M. Search for Related Content PubMed PubMed Citation Articles by Laurie, S. A. Articles by Lorence, R. M.

A Phase 1 Clinical Study of Intravenous Administration of PV701, an Oncolytic Virus, Using Two-Step Desensitization

Authors' Affiliations: ¹ Division of Medical Oncology and ² Centre for Cancer Therapeutics, Ottawa Hospital Regional Cancer Centre, University of Ottawa, Ottawa, Ontario, Canada and ³ Wellstat Biologics Corp., Gaithersburg, Maryland

Requests for reprints: Scott A. Laurie, Division of Medical Oncology, Ottawa Hospital Regional Cancer Centre, University of Ottawa, 503 Smyth Road, Ottawa, Ontario, Canada K1H 1C4. Phone: 613-737-7700, ext. 70173; Fax: 613-247-3511; E-mail: slaurie{at}ottawahospital.on.ca.

Purpose: In a previous phase 1 study, adverse events, especially flu-like symptoms, were observed mainly following the first i.v. bolus dose of PV701, an oncolytic Newcastle disease virus. Desensitization to adverse events of subsequent doses occurred, allowing a 10-fold increase in the maximum tolerated dose for these doses. Although one-step desensitization (a single desensitizing dose with higher subsequent doses) addressed the tolerability of high repeat doses, additional testing was required to further improve tolerability of the initial dose. This study tested the hypothesis that two-step desensitization, using two dose increments before high repeat doses, would be well tolerated.

Experimental Design: Sixteen adults with incurable solid tumors were enrolled. Cycles consisted of six PV701 doses over 2 weeks followed by a 1-week rest. Doses 1 to 2 were 1 and 12 x 10⁹ plaque-forming units (pfu)/m², respectively, whereas doses 3 to 6 were escalated by cohort from 24 to 120 x 10⁹ pfu/m².

Results: No dose-limiting toxicities were observed, permitting dose escalation through cohort 4 (1, 12, 120, 120, 120, 120 x 10⁹ pfu/m²). Mild flu-like symptoms were common following the first infusion, diminished with repeated dosing, and were less pronounced than those seen previously. Tumor regression was observed in a patient with anal carcinoma who enrolled with stable disease following palliative radiotherapy. Four patients with clearly progressing cancer before enrollment had disease stabilization of 6 months.

Conclusions: This novel two-step desensitization improved patient tolerability compared with the previous regimen. Toxicities were predictable and manageable. PV701, the first oncolytic virus to enter phase 1 i.v. testing, continues to show single-agent activity, warranting planned phase 2 trials.

This article has been cited by other articles:

				S. J. Goebel, J. Taylor, B. C. Barr, T. E. Kiehn, H. R. Castro-Malaspina, C. V. Hedvat, K. A. Rush-Wilson, C. D. Kelly, S. W. Davis, W. A. Samsonoff, et al. Isolation of Avian Paramyxovirus 1 from a Patient with a Lethal Case of Pneumonia J. Virol., November 15, 2007; 81(22): 12709 - 12714. [Abstract] [Full Text] [PDF]

				S. J. Hotte, R. M. Lorence, H. W. Hirte, S. R. Polawski, M. K. Bamat, J. D. O'Neil, M. S. Roberts, W. S. Groene, and P. P. Major An Optimized Clinical Regimen for the Oncolytic Virus PV701 Clin. Cancer Res., February 1, 2007; 13(3): 977 - 985. [Abstract] [Full Text] [PDF]