[Phase III randomized clinical trial of intratumoral injection of E1B gene-deleted adenovirus (H101) combined with cisplatin-based chemotherapy in treating squamous cell cancer of head and neck or esophagus].
OBJECTIVE
H101 is an E1B-55 kDa gene-deleted replication-selective adenovirus, which showed a significant antitumor activity. This study was to compare effects and toxicities of intratumoral H101 injection combined with cisplatin plus 5-fluorouracil (PF) regimen or adriamycin plus 5-fluorouracil (AF) regimen versus PF or AF regimen alone in treating patients with head and neck or esophagus squamous cell cancer.


METHODS
A total of 160 patients were recruited. PF regimen (cisplatin 20 mg/m(2) ivgtt, qd x 5d; 5-fluorouracil 500 mg/m(2) ivgtt, qd x 5d) was administered to patients have no history of PF chemotherapy,or sensitive to PF chemotherapy,while AF regimen (adriamycin 50 mg/m(2) iv,d1; 5-fluorouracil 500 mg/m(2) ivgtt, qd x 5d) was administered to patients didn't response to PF regimen. All patients were randomized to either receive intratumoral H101 injection (5.0 x 10(11)-1.5 x 10(12) VP/day for 5 consecutive days every 3 weeks) or not. Treatment repeated every 3 weeks,all patients have to receive at least 2 cycles of chemotherapy.


RESULTS
Among 123 accordant patients,overall response rate of PF plus H101 group (group A1) was 78.8% (41/52),of PF alone group (group B1) was 39.6% (21/53),of AF plus H101 group (group A2) was 50.0% (7/14),of AF alone group (group B2) was 50.0% (2/4). Differences of response rates between group A1 and group B1,between group A1+A2 and group B1+B2 were significant (P=0.000). Main side effects were fever (45.7%), injection site reaction (28.3%),and influenza-like symptoms (9.8%).


CONCLUSIONS
Intratumoral H101 injection showed a distinct efficacy in patients with squamous cell cancer of head and neck or esophagus,and was relatively safe.
Xia
Zhong-Jun
ZJ
Department of Medicine, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong 510060, P.R. China.
Chang
Jian-Hua
JH
Zhang
Li
L
Jiang
Wen-Qi
WQ
Guan
Zhong-Zhen
ZZ
Liu
Ji-Wei
JW
Zhang
Yang
Y
Hu
Xiao-Hua
XH
Wu
Guo-Hua
GH
Wang
Hua-Qing
HQ
Chen
Zheng-Chang
ZC
Chen
Jian-Chao
JC
Zhou
Qing-Hua
QH
Lu
Jian-Wei
JW
Fan
Qing-Xia
QX
Huang
Jian-Jin
JJ
Zheng
Xiao
X
D000256:Adenoviridae / Q000235:genetics / Q000502:physiology*; D017501:Adenovirus E1B Proteins / Q000172:deficiency* / Q000235:genetics; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001691:Biological Therapy / Q000009:adverse effects; D002294:Carcinoma, Squamous Cell / Q000628:therapy; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage; D004938:Esophageal Neoplasms / Q000628:therapy*; D005260:Female; D005334:Fever / Q000209:etiology; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D015552:Injections, Intralesional; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000628:therapy*
D017501:Adenovirus E1B Proteins; D004317:Doxorubicin; D002945:Cisplatin; D005472:Fluorouracil