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.
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.
Khuri
F R
FR
The University of Texas M. D. Anderson Cancer Center, Division of Cancer Medicine, Houston, Texas, USA.
Nemunaitis
J
J
Ganly
I
I
Arseneau
J
J
Tannock
I F
IF
Romel
L
L
Gore
M
M
Ironside
J
J
MacDougall
R H
RH
Heise
C
C
Randlev
B
B
Gillenwater
A M
AM
Bruso
P
P
Kaye
S B
SB
Hong
W K
WK
Kirn
D H
DH
D000260:Adenoviruses, Human / Q000235:genetics* / Q000502:physiology; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology / Q000628:therapy; D002945:Cisplatin / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods*; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy*; D014779:Virus Replication
D002945:Cisplatin; D005472:Fluorouracil