[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].

BACKGROUND & 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%). CONCLUSION: Intratumoral H101 injection showed a distinct efficacy in patients with squamous cell cancer of head and neck or esophagus,and was relatively safe.

Intra-tumor injection of H101, a recombinant adenovirus, in combination with chemotherapy in patients with advanced cancers: a pilot phase II clinical trial.

AIM: 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. CONCLUSION: 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.

[Phase II clinical study of intratumoral H101, an E1B deleted adenovirus, in combination with chemotherapy in patients with cancer].

BACKGROUND & 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. CONCLUSION: 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.