title: A Phase I study of KH901, a conditionally replicating granulocyte-macrophage colony-stimulating factor: armed oncolytic adenovirus for the treatment of head and neck cancers.
abstract: BACKGROUND
  KH901 is a conditionally replicating oncolytic adenovirus, which reported selectively replicates in and lyses telomerase-positive tumor cells and expresses granulocyte macrophase colony-stimulating factor (GM-CSF). To determine the safety, feasibility and biological activity of KH901, a conditionally replicating oncolytic adenovirus, in patients with recurrent head and neck cancer (HNC).
  
  
  RESULTS
  Treatment was well tolerated, with the main toxicity being grade 1/2 flu-like symptoms. Dose-limiting toxicity was not reached in either single dose groups or multiple dose groups. KH901 was detected in urine, but little was found in feces. Interestingly, a second peak of detectable KH901 genome found in the circulation in majority of patients tested between 2 and 4 days after treatment. High level of GM-CSF in circulation was detected in all single dose patients 12 h and became undetectable 15 days following injection. All 23 patients treated showed an increase in neutralizing antibody to adenovirus.
  
  
  METHODS
  Twenty-three patients with recurrent HNC was administered by intratumoral injection in two parts of trial. In the single dose escalating portion, four cohort of 13 patients received a single injection of KH901 at a dose of 3 x 10(11) virus particle (vp), 1 x 10(12) vp, 3 x 10(12) vp and 1 x 10(13) vp, respectively, while in the multiple dose portion each cohort of six patients received twice weekly a total of six injections at a dose of either 1 x 10(12) vp or 3 x 10(12) vp. Toxicity was assessed using NCIC criteria. Tumor response was assessed by clinical and radiological measurement. Blood samples were taken to detect adenovirus DNA, GM-CSF expression and neutralizing antibody to adenovirus.
  
  
  CONCLUSIONS
  These preliminary results showed that intratumoral administration of KH901 was feasible, well tolerated and associated with biological activity, further investigation of KH901, particularly in combination with systemic chemotherapy, was warranted.
authors.affiliation: Department of Medical Oncology, Cancer Hospital of Fudan University, Shanghai, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Chang
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Zhao
authors.forename: Xianghua
authors.initials: X
authors.lastname: Wu
authors.forename: Ye
authors.initials: Y
authors.lastname: Guo
authors.forename: Haiyi
authors.initials: H
authors.lastname: Guo
authors.forename: Junnin
authors.initials: J
authors.lastname: Cao
authors.forename: Yong
authors.initials: Y
authors.lastname: Guo
authors.forename: Delun
authors.initials: D
authors.lastname: Lou
authors.forename: Dechao
authors.initials: D
authors.lastname: Yu
authors.forename: Jin
authors.initials: J
authors.lastname: Li
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000257:Adenoviridae Infections / Q000473:pathology / Q000628:therapy / Q000821:virology; D000328:Adult; D000368:Aged; D003588:Cytopathogenic Effect, Viral; D004279:DNA, Viral / Q000235:genetics; D005240:Feasibility Studies; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D006258:Head and Neck Neoplasms / Q000473:pathology / Q000628:therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology / Q000628:therapy / Q000821:virology; D050130:Oncolytic Virotherapy; D016133:Polymerase Chain Reaction; D014779:Virus Replication
chemical_list: D004279:DNA, Viral; D016178:Granulocyte-Macrophage Colony-Stimulating Factor