title: Phase I trial of intravenous administration of PV701, an oncolytic virus, in patients with advanced solid cancers.
abstract: 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.
authors: Cancer Center at Hackensack University Medical Center, Hackensack, NJ 07601, USA. apecora@humed.com
authors: Andrew L
authors: AL
authors: Pecora
authors: Naiyer
authors: N
authors: Rizvi
authors: Gary I
authors: GI
authors: Cohen
authors: Neal J
authors: NJ
authors: Meropol
authors: Daniel
authors: D
authors: Sterman
authors: John L
authors: JL
authors: Marshall
authors: Stuart
authors: S
authors: Goldberg
authors: Peter
authors: P
authors: Gross
authors: James D
authors: JD
authors: O'Neil
authors: William S
authors: WS
authors: Groene
authors: M Scot
authors: MS
authors: Roberts
authors: Harvey
authors: H
authors: Rabin
authors: Michael K
authors: MK
authors: Bamat
authors: Robert M
authors: RM
authors: Lorence
mesh_terms: 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