Nature Medicine
6, 879 - 885 (2000)
doi:10.1038/78638
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 cancerFadlo R. Khuri1, John Nemunaitis3, Ian Ganly4, James Arseneau3, Ian F. Tannock7, Larry Romel8, Martin Gore5, Janet Ironside6, R.H. MacDougall6, Carla Heise8, Britta Randlev8, Ann M. Gillenwater2, Patricia Bruso2, Stanley B. Kaye4, Waun Ki Hong1
& David H. Kirn91
The University of Texas M. D. Anderson Cancer Center,
Division of Cancer Medicine Houston, Texas
2
The University of Texas M. D. Anderson Cancer Center,
Division of Surgery, Houston, Texas; 3
U.S. Oncology, Dallas, Texas,
4
Beatson Oncology Institute, University of Glasgow,
Glasgow Scotland
5
Royal Marsden Hospital, London,
England, 6
Western General Hospital, Edinburgh,
Scotland; 7
Princess Margaret Hospital, Toronto,
Ontario; 8
ONYX Pharmaceutical, Richmond,
California; 9
Imperial Cancer Research Fund, London,
England
Correspondence should be addressed to Fadlo R. Khuri fkhuri@mdanderson.orgONYX-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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