[Phase II clinical study of intratumoral H101, an E1B deleted adenovirus, in combination with chemotherapy in patients with cancer].
OBJECTIVE
In recent years,great development have been made in cancer therapeutics with replication-competent viruses (oncolytic viruses), E1B deleted adenovirus is one of promising viruses. The current study was designed to evaluate the efficacy and toxicity of intratumoral H101, a E1B-deleted adenovirus, in combination with chemotherapy on patients with cancer.


METHODS
A total of 50 patients with malignant tumors in multiple centers clinical trial were treated with H101, 0.5ml 5x10(11) viral particle per day for 5 consecutive days every three weeks. Routine chemotherapy was performed at the same time. And the efficacy and toxicity were recorded.


RESULTS
Among 46 valuable cases, the overall response rate was 30.4%. The response rate was 28.0% (14/50) among ITT population, including 3 complete response (CR) and 11 partial response (PR). The overall response rate of control lesion was 13.0%, including 1 case of CR and 5 cases of PR. Thus, the response rate in injected lesion is clearly higher than that in control lesion (P< 0.001). Main side effects were injection site pain (26.9%) and fever (30.2%). Grade 1 hepatic dysfunction was found in 4 patients, grade 2 in 1 patients, grade 4 in 1 patients. Grade 4 hematological toxicities were found in 4 patients.


CONCLUSIONS
The study showed that the combination of genetically modified adenovirus (H101) and chemotherapy possessed some effect for treating the patients with refractory malignant tumors, and the toxicities were lower, well tolerated.
Xu
Rui-Hua
RH
Department of Medicine,Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, PR China.
Yuan
Zhong-Yu
ZY
Guan
Zhong-Zhen
ZZ
Cao
Ye
Y
Wang
Hua-Qing
HQ
Hu
Xiao-Hua
XH
Feng
Ji-Feng
JF
Zhang
Yang
Y
Li
Fang
F
Chen
Zheng-Tang
ZT
Wang
Jie-Jun
JJ
Huang
Jian-Jin
JJ
Zhou
Qing-Hua
QH
Song
San-Tai
ST
D000256:Adenoviridae / Q000235:genetics / Q000502:physiology*; D017501:Adenovirus E1B Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001691:Biological Therapy / Q000009:adverse effects; D003131:Combined Modality Therapy / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000628:therapy*; D016896:Treatment Outcome
D017501:Adenovirus E1B Proteins; D000970:Antineoplastic Agents