PMID- 17346107
OWN - NLM
STAT- MEDLINE
DCOM- 20070330
LR  - 20191026
IS  - 1873-5576 (Electronic)
IS  - 1568-0096 (Linking)
VI  - 7
IP  - 2
DP  - 2007 Mar
TI  - Phase 1 clinical experience using intravenous administration of PV701, an 
      oncolytic Newcastle disease virus.
PG  - 157-67
AB  - PV701 is a naturally-attenuated, non-recombinant, oncolytic strain of Newcastle 
      disease virus that displays preclinical intravenous (IV) efficacy. PV701 is 
      selective at killing human cancer cells versus normal human cells based on tumor 
      specific defects in the interferon (IFN)-mediated antiviral response. This 
      oncolytic virus displays a broad spectrum of antitumor activity in vitro and in 
      vivo. Preclinical models successfully predicted key clinical parameters including 
      the mechanism of toxicity, two complementary strategies (desensitization and slow 
      infusion) to reduce toxicity, and the starting dose for phase 1 trials. In three 
      phase 1 trials of 114 patients using IV administration of PV701, Wellstat 
      Biologics Corporation has evaluated the effects of dose, schedule, and infusion 
      rate for PV701. Three general classes of side effects were seen: flu-like 
      symptoms; tumor-site-specific adverse events (AEs); and infusion reactions. The 
      first PV701 dose desensitized the patient to the side effects of further doses, 
      allowing a marked increase in the maximum tolerated dose for subsequent doses 
      compared to the first dose. Tumor responses were first noted at the higher doses 
      achieved using desensitization. In the most recent phase 1 trial of 19 patients 
      at Hamilton, Ontario, that employed desensitization, high repeat doses, and a 
      slower infusion rate (Hamilton Regimen), there were six responses (4 major; 2 
      minor) and a total of six patients with survival for at least 2 years. In 
      addition, patient tolerability improved using the Hamilton Regimen compared to IV 
      bolus dosing used previously. Phase 2 studies of this novel biologic agent are 
      about to begin.
FAU - Lorence, Robert M
AU  - Lorence RM
AD  - Wellstat Biologics Corporation, Gaithersburg, MD 20878, USA. 
      rlorence@wellstatbiologics.com
FAU - Roberts, M Scot
AU  - Roberts MS
FAU - O'Neil, James D
AU  - O'Neil JD
FAU - Groene, William S
AU  - Groene WS
FAU - Miller, Jeffrey A
AU  - Miller JA
FAU - Mueller, Stephen N
AU  - Mueller SN
FAU - Bamat, Michael K
AU  - Bamat MK
LA  - eng
PT  - Journal Article
PT  - Review
PL  - Netherlands
TA  - Curr Cancer Drug Targets
JT  - Current cancer drug targets
JID - 101094211
SB  - IM
MH  - Animals
MH  - Clinical Trials, Phase I as Topic/methods
MH  - Humans
MH  - Infusions, Intravenous
MH  - Injections, Intravenous
MH  - Neoplasms/*therapy
MH  - *Newcastle disease virus/genetics/physiology
MH  - *Oncolytic Virotherapy/adverse effects
MH  - Research Design
MH  - Treatment Outcome
MH  - Virus Replication
RF  - 41
EDAT- 2007/03/10 09:00
MHDA- 2007/03/31 09:00
CRDT- 2007/03/10 09:00
PHST- 2007/03/10 09:00 [pubmed]
PHST- 2007/03/31 09:00 [medline]
PHST- 2007/03/10 09:00 [entrez]
AID - 10.2174/156800907780058853 [doi]
PST - ppublish
SO  - Curr Cancer Drug Targets. 2007 Mar;7(2):157-67. doi: 10.2174/156800907780058853.