ONYX-015 is an adenovirus with the E1B 55-kDa gene deleted, engineered to selectively replicate in and lyse p53-deficient cancer cells while sparing normal cells. Although ONYX-015 and chemotherapy have demonstrated anti-tumoral activity in patients with recurrent head and neck cancer, disease recurs rapidly with either therapy alone. We undertook a phase II trial of a combination of intratumoral ONYX-015 injection with cisplatin and 5-fluorouracil in patients with recurrent squamous cell cancer of the head and neck. There were substantial objective responses, including a high proportion of complete responses. By 6 months, none of the responding tumors had progressed, whereas all non-injected tumors treated with chemotherapy alone had progressed. The toxic effects that occurred were acceptable. Tumor biopsies obtained after treatment showed tumor-selective viral replication and necrosis induction.
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We thank the following individuals for their assistance on this clinical trial and on this manuscript: P. Coldiron, D. Davies, O. Diri, J. Kuhn, S. Landers, T. McCarty, V. Papadimitrakopoulou, M. Posner, M. Propst, P. Roo, L. Siu, J. Starr, K. Sultan, S. Toney and P. Trown.
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Khuri, F., Nemunaitis, J., Ganly, I. et al. A controlled trial of intratumoral ONYX-015, a selectively-replicating adenovirus, in combination with cisplatin and 5-fluorouracil in patients with recurrent head and neck cancer. Nat Med 6, 879–885 (2000). https://doi.org/10.1038/78638
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