Phase I trial of intravenous administration of PV701, an oncolytic virus, in patients with advanced solid cancers.
OBJECTIVE
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.


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 10(9) plaque-forming units (PFU)/m(2) was established for outpatient dosing. After an initial dose of 12 x 10(9) PFU/m(2), patients tolerated an MTD for subsequent doses of 120 x 10(9) PFU/m(2). 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.


CONCLUSIONS
PV701 warrants further study as a novel therapeutic agent for cancer patients.
Pecora
Andrew L
AL
Cancer Center at Hackensack University Medical Center, Hackensack, NJ 07601, USA. apecora@humed.com
Rizvi
Naiyer
N
Cohen
Gary I
GI
Meropol
Neal J
NJ
Sterman
Daniel
D
Marshall
John L
JL
Goldberg
Stuart
S
Gross
Peter
P
O'Neil
James D
JD
Groene
William S
WS
Roberts
M Scot
MS
Rabin
Harvey
H
Bamat
Michael K
MK
Lorence
Robert M
RM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D009522:Newcastle disease virus / Q000235:genetics*; D016896:Treatment Outcome; D014779:Virus Replication