[Clinical tolerance trial on recombinant human endostatin adenovirus].
OBJECTIVE
Recently, some phase I trials on endostatin has shown broad antitumor activity with low toxicity. This study was to determine the maximal tolerant dose (MTD) of recombinant human endostatin adenovirus Ad-Es for human.


METHODS
For the sake of safety, 1 patient was treated with 1x10(10) VP Ad-Es single intratumoral injection in advance. A total of 14 patients with malignant tumors received weekly intratumoral injection of Ad-Es in a dose-escalation manner (1x10(11) VP, 5x10(11) VP, 1x10(12) VP) for 2 weeks.


RESULTS
Toxicity profiles in all 15 cases were available. All patients tolerated well. No dose-limited toxicity (DLT) and serious adverse event were observed during treatment. Main adverse events were injection reaction (40.0%) and fever (53.3%). One patient with nasopharyngeal carcinoma had a minor response, 12 patients showed stable disease and 2 patients had progressive disease.


CONCLUSIONS
Ad-Es is well tolerated up to 1x10(12) VP. The recommended dose for phase II trial is 1x10(12) VP intratumor injection for 4 consecutive weeks.
Cao
Ye
Y
State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, 510060, PR China.
Li
Su
S
Li
Hong-Li
HL
Li
Yu-Hong
YH
Zhang
Dong-Sheng
DS
Guo
Ying
Y
Li
Xiao-Ling
XL
Lin
Xu-Bin
XB
Huang
Wen-Lin
WL
Jiang
Wen-Qi
WQ
D000256:Adenoviridae / Q000235:genetics*; D000328:Adult; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use; D004361:Drug Tolerance; D043169:Endostatins / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use*; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D015552:Injections, Intralesional; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000628:therapy*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use; D012509:Sarcoma / Q000628:therapy*
D020533:Angiogenesis Inhibitors; D043169:Endostatins; D011994:Recombinant Proteins