Intra-tumor injection of H101, a recombinant adenovirus, in combination with chemotherapy in patients with advanced cancers: a pilot phase II clinical trial.
OBJECTIVE
H101, an E1B 55 kD gene deleted adenovirus, has been shown to possess oncolysis activity experimentally and proved to be safe in preliminary phase I study. The current study was designed to evaluate its anti-tumor activity and toxicity in combination with chemotherapy in patients with late stage cancers.


METHODS
H101 5.0x10(11) virus particles were given by intra-tumor injection daily for five consecutive days at every three-week cycle, combined with routine chemotherapy, to one of the tumor lesions of 50 patients with different malignant tumors. Tumor lesions without H101 injection in the same individuals were used as controls. The efficacy and toxicity were recorded.


RESULTS
Forty-six patients were evaluable with a 30.4% response rate. H101 injection in combination with chemotherapy induced three complete response (CR) and 11 partial response (PR), giving an overall response rate of 28.0% (14/50) among intention-to-treat patients. The response rate for the control lesions was 13.0%, including one case with CR and five cases with PR, which was significantly lower than that for the injected lesions (P<0.05). Main side effects were fever (30.2%) and pain at the injected sites (26.9%). Grade 1 hepatic dysfunction was found in four patients, grade 2 in one patient, and grade 4 in one patient. Hematological toxicity (grade 4) was found in four patients.


CONCLUSIONS
Intra-tumor injection of the genetically engineered adenovirus H101 exhibits potential anti-tumor activity to refractory malignant tumors in combination with chemotherapy. Low toxicity and good tolerance of patients to H101were observed.
Lu
Wei
W
Cancer Center, Second Affiliated Hospital, Medical College, Zhejiang University, 88 Jiefang Road, Hangzhou 310009, Zhejiang Province, China.
Zheng
Shu
S
Li
Xu-Feng
XF
Huang
Jian-Jin
JJ
Zheng
Xiao
X
Li
Zhen
Z
D000256:Adenoviridae / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D017501:Adenovirus E1B Proteins / Q000235:genetics*; D000917:Antibody Formation; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001691:Biological Therapy / Q000009:adverse effects; D003131:Combined Modality Therapy; D005260:Female; D016679:Genome, Viral; D006801:Humans; D007150:Immunohistochemistry; D015552:Injections, Intralesional; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D011994:Recombinant Proteins / Q000235:genetics; D016896:Treatment Outcome
D017501:Adenovirus E1B Proteins; D000970:Antineoplastic Agents; D011994:Recombinant Proteins