title: REO-001: A phase I trial of percutaneous intralesional administration of reovirus type 3 dearing (Reolysin®) in patients with advanced solid tumors.
abstract: OBJECTIVE
  This open-labeled, phase I clinical trial was designed to determine the safety and tolerability of percutaneous intralesional administration of wild-type oncolytic revovirus type 3 Dearing (Reolysin®) in cancer patients with accessible and evaluable disease, who had otherwise failed to improve on standard cancer interventions.
  
  
  METHODS
  An escalating dose of Reolysin® starting from up to 10(10) plague forming units (PFU) was administered to each cohort of three patients per dose level. Viral shedding, reovirus neutralizing antibody response, toxicity and clinical response were assessed.
  
  
  RESULTS
  Nineteen patients with various advanced solid tumors were treated. The most common toxicities related to treatment were grade 2 (or less) local erythema and transient flu like symptoms. Viral shedding was not seen in cerebral spinal fluid (CSF), urine and stool samples in all patients. Rising viral antibody titres were seen in all patients. In addition, we observed some evidence of local target tumor response activity in 7/19 patients (37 %) at the end of six or more weeks follow-up, with one patient exhibiting a complete response (CR), two a partial response (PR), and four stable disease (SD) to the local injected lesion.
  
  
  CONCLUSIONS
  Reolysin® is well tolerated given intralesionaly, with DLT/MTD not reached at a dose of 10(10) PFU. The favorable toxicity profile, lack of viral shedding and possible therapeutic activity has made this unattenuated oncolytic reovirus an attractive cancer therapeutic agent for ongoing clinical studies, including in the setting of locally advanced accessible disease for palliation of symptoms.
authors.affiliation: Tom Baker Cancer Center, 1331-29th Street NW, Calgary, AB, T2N 4N2, Canada. don.morris@albertahealthservices.ca
authors.forename: Don G
authors.initials: DG
authors.lastname: Morris
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Feng
authors.forename: Lisa M
authors.initials: LM
authors.lastname: DiFrancesco
authors.forename: Kevin
authors.initials: K
authors.lastname: Fonseca
authors.forename: Peter A
authors.initials: PA
authors.lastname: Forsyth
authors.forename: Alexander H
authors.initials: AH
authors.lastname: Paterson
authors.forename: Matt C
authors.initials: MC
authors.lastname: Coffey
authors.forename: Brad
authors.initials: B
authors.lastname: Thompson
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000097:blood; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006261:Headache / Q000209:etiology; D006801:Humans; D008297:Male; D012089:Mammalian orthoreovirus 3; D008875:Middle Aged; D009325:Nausea / Q000209:etiology; D009369:Neoplasms / Q000097:blood / Q000628:therapy* / Q000821:virology; D050130:Oncolytic Virotherapy / Q000009:adverse effects; D050504:Oncolytic Viruses; D017201:Virus Shedding; D014839:Vomiting / Q000209:etiology
chemical_list: D000914:Antibodies, Viral; D000970:Antineoplastic Agents