Phase II trial of intratumoral administration of ONYX-015, a replication-selective adenovirus, in patients with refractory head and neck cancer.
OBJECTIVE
To determine the safety, humoral immune response replication, and activity of multiple intratumoral injections of ONYX-015 (replication selective adenovirus) in patients with recurrent squamous cell carcinoma of the head and neck (SCCHN).


METHODS
This phase II trial enrolled patients with SCCHN who had recurrence/relapse after prior conventional treatment. Patients received ONYX-015 at a dose of 2 x 10(11) particles via intratumoral injection for either 5 consecutive days (standard) or twice daily for 2 consecutive weeks (hyperfractionated) during a 21-day cycle. Patients were monitored for tumor response, toxicity, and antibody formation.


RESULTS
Forty patients (30 standard and 10 hyperfractionated) received 533 injections of ONYX-015. Standard treatment resulted in 14% partial to complete regression, 41% stable disease, and 45% progressive disease rates. Hyperfractionated treatment resulted in 10% complete response, 62% stable disease, and 29% progressive disease rates. Treatment-related toxicity included mild to moderate fever (67% overall) and injection site pain (47% on the standard regimen, 80% on the hyperfractionated regimen). Detectable circulating ONYX-015 genome suggestive of intratumoral replication was identified in 41% of tested patients on days 5 and 6 of cycle 1; 9% of patients had evidence of viral replication 10 days after injection during cycle 1, and no patients had evidence of replication > or = 22 days after injection.


CONCLUSIONS
ONYX-015 can be safely administered via intratumoral injection to patients with recurrent/refractory SCCHN. ONYX-015 viremia is transient. Evidence of modest antitumoral activity is suggested.
Nemunaitis
J
J
US Oncology, Dallas, TX 75246, USA. John.Nemunaitis@USOncology.com
Khuri
F
F
Ganly
I
I
Arseneau
J
J
Posner
M
M
Vokes
E
E
Kuhn
J
J
McCarty
T
T
Landers
S
S
Blackburn
A
A
Romel
L
L
Randlev
B
B
Kaye
S
S
Kirn
D
D
D017501:Adenovirus E1B Proteins; D000260:Adenoviruses, Human / Q000235:genetics / Q000502:physiology; D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000628:therapy*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D015316:Genetic Therapy; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000628:therapy*; D006801:Humans; D015552:Injections, Intralesional; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000628:therapy*; D009500:Neutralization Tests; D012074:Remission Induction; D014766:Viremia; D014779:Virus Replication
D017501:Adenovirus E1B Proteins