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Phase I Trial of Intravenous Administration of PV701, an Oncolytic Virus, in Patients With Advanced Solid Cancers

From the Cancer Center at Hackensack University Medical Center, Hackensack, NJ; Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC; The Cancer Center at Greater Baltimore Medical Center, Baltimore, and Pro-Virus, Inc, Gaithersburg, MD; and Fox Chase Cancer Center and University of Pennsylvania Medical Center, Philadelphia, PA.

Address reprint requests to Andrew L. Pecora, MD, Hackensack University Medical Center, Northern New Jersey Cancer Center, 20 Prospect Ave, Suite 400, Hackensack, NJ 07601; email: apecora@ humed.com.

PURPOSE: PV701, a replication-competent strain of Newcastle disease virus, causes regression of tumor xenografts after intravenous administration. This phase I study was designed to define the maximum-tolerated dose (MTD) and safety of single and multiple intravenous doses of PV701 as a single agent in patients with cancer.

PATIENTS AND METHODS: Seventy-nine patients with advanced solid cancers that were unresponsive to standard therapy were enrolled. Four PV701 intravenous dosing regimens were evaluated: (1) single dose: one dose every 28 days; (2) repeat dose: three doses in 1 week every 28 days; (3) desensitizing: one lower dose followed by two higher doses in 1 week every 28 days; and (4) two week: one lower dose followed by five higher doses over 2 weeks every 21 days.

RESULTS: A 100-fold dose intensification was achieved over 195 cycles. A first-dose MTD of 12 x 10⁹ plaque-forming units (PFU)/m² was established for outpatient dosing. After an initial dose of 12 x 10⁹ PFU/m², patients tolerated an MTD for subsequent doses of 120 x 10⁹ PFU/m². The most common adverse events were flu-like symptoms that occurred principally after the first dose and were decreased in number and severity with each subsequent dose. Tumor site–specific adverse events and acute dosing reactions were also observed but not cumulative toxicity. Objective responses occurred at higher dose levels, and progression-free survival ranged from 4 to 31 months. Tumor tissue from one patient was obtained after 11 months of therapy and showed evidence of PV701 particles budding from the tumor cell membrane by electron microscopy and a pronounced lymphoplasmacytic infiltrate by histologic examination.

CONCLUSION: PV701 warrants further study as a novel therapeutic agent for cancer patients.

Presented in part at the Thirty-Seventh Annual Meeting of the American Society of Clinical Oncology, San Francisco, CA, May 12-15, 2001.

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