Phase II trial of intratumoral administration of ONYX-015, a replication-selective adenovirus, in patients with refractory head and neck cancer.

Abstract

PURPOSE:

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).

PATIENTS AND 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.

CONCLUSION:

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.

• Authors: J Nemunaitis, F Khuri, I Ganly, J Arseneau, M Posner, E Vokes, J Kuhn, T McCarty, S Landers, A Blackburn, L Romel, B Randlev, S Kaye, D Kirn
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 19 Issue 2 Pg. 289-98 (Jan 15 2001) ISSN: 0732-183X [Print] United States
• PMID: 11208818 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Multicenter Study)

Chemical References

• Adenovirus E1B Proteins

Topics

• Adenovirus E1B Proteins
• Adenoviruses, Human (genetics, physiology)
• Adult
• Aged
• Carcinoma, Squamous Cell (genetics, therapy)
• Female
• Gene Expression Regulation, Neoplastic
• Genes, p53
• Genetic Therapy
• Head and Neck Neoplasms (genetics, therapy)
• Humans
• Injections, Intralesional
• Male
• Middle Aged
• Neoplasm Recurrence, Local (genetics, therapy)
• Neutralization Tests
• Remission Induction
• Viremia
• Virus Replication