A phase I trial of intravenous CG7870, a replication-selective, prostate-specific antigen-targeted oncolytic adenovirus, for the treatment of hormone-refractory, metastatic prostate cancer

Mol Ther. 2006 Jul;14(1):107-17. doi: 10.1016/j.ymthe.2006.02.011. Epub 2006 May 9.


CG7870 is a replication-selective oncolytic adenovirus genetically engineered to replicate preferentially in prostate tissue. In a previous phase I/II clinical trial of intraprostatic delivery of CG7870 for locally recurrent prostate cancer this virus was well tolerated. In this phase I study CG7870 was administered as a single intravenous infusion in a group-sequential dose escalation design (1 x 10(10) to 6 x 10(12) viral particles (vp)) to 23 patients with hormone-refractory metastatic prostate cancer. Flulike symptoms (fever, fatigue, rigors, nausea, and/or vomiting) were the most common adverse events. Three therapy-related grade 3 adverse events were reported, one of which (fatigue) was serious. At doses greater than 10(12) vp all five patients experienced asymptomatic grade 1 to 2 transaminitis and/or isolated d-dimer elevations starting on day 2 through 8; dose escalation was therefore halted at 6 x 10(12) vp. All tested patients had CG7870 genomes present in the peripheral blood for at least 90 minutes after infusion; patients in the highest dose group had persistence of genomes through 29 days. A "secondary" or "delayed" peak in plasma CG7870 genome copies (defined as a >10-fold increase in CG7870 genomes from nadir concentration) suggestive of active viral replication and shedding into the bloodstream was detected in 16/23 (70%) patients. CG7870 was detected in the saliva of 3 patients, whereas all urine samples tested negative. All patients developed antibodies to CG7870. Dose-related increases in interleukins 6 and 10 (IL-6, IL-10) blood levels were detected. The peak IL-6 concentration after CG7870 treatment was associated with a transient, asymptomatic decrease in blood pressure. No partial or complete prostate-specific antigen (PSA) responses were observed; however, 5 patients had a decrease in serum PSA of 25% to 49% following a single treatment, including 3 of 8 patients at the highest dose levels.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenoviridae / genetics*
  • Adenoviridae / immunology
  • Aged
  • Aged, 80 and over
  • Antibodies, Viral / blood
  • Blood Pressure / drug effects
  • Cytokines / blood
  • DNA Replication / genetics
  • Dose-Response Relationship, Drug
  • Genetic Therapy / adverse effects
  • Genetic Therapy / methods*
  • Genetic Vectors / administration & dosage
  • Genetic Vectors / genetics
  • Genetic Vectors / pharmacokinetics
  • Humans
  • Infusions, Intravenous
  • Interleukin-10 / blood
  • Interleukin-6 / blood
  • Male
  • Middle Aged
  • Prostate-Specific Antigen / blood*
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / therapy*
  • Saliva / metabolism
  • Tissue Distribution
  • Treatment Outcome


  • Antibodies, Viral
  • Cytokines
  • Interleukin-6
  • Interleukin-10
  • Prostate-Specific Antigen