Clinical study of recombinant adenovirus-p53 combined with fractionated stereotactic radiotherapy for hepatocellular carcinoma

Cancer Center, Daping Hospital and Institute of Surgery Research, Third Military Medical University, 400042, Chongqing, China.
Journal of Cancer Research and Clinical Oncology (Impact Factor: 3.08). 10/2009; 136(4):625-30. DOI: 10.1007/s00432-009-0701-6
Source: PubMed


The purpose of our study was to evaluate the feasibility and treatment outcomes of recombinant adenovirus-p53 (rAd-p53, trademarked as Gendicine) combined with fractionated stereotactic radiotherapy (fSRT) in treatment of primary hepatocellular carcinoma (HCC).
We randomly enrolled 40 patients with HCC treated by fSRT alone (fSRT group) or rAd-p53 combined with fSRT (combined group). Tumor size was 2-5.2 cm (average 3.2 cm). We prescribed 50 Gy in 10 fractions at the 50%-80% isodose line of the planning target volume for 2 weeks in two groups. The combined group was treated with two intratumoral injections of rAd-p53 on day 1 and 8 while fSRT started on day 3. Tumor response was assessed after treatment using modified WHO criteria. The follow-up period was 11-44 months (median 35 months).
The overall response rate of fSRT group was 70%, with 4 patients showing complete response (20%), 10 partial response (50%) and 6 stable disease (30%). Correspondingly the overall response rate of combined group was 85%, with 7 patients showing complete response (35%), 10 partial response (50%) and 3 stable disease (15%). The 1-year survival rates of fSRT group and combined group were 70.0% and 90.0%, respectively. The 1-year disease-free survival rates of fSRT group and combined group were 65% and 85%, respectively. These treatments were well tolerated, because grade 3 or 4 toxicity was not observed.
These results suggest that rAd-p53 combined with fSRT is a relatively safe and effective method for treating primary hepatocellular carcinoma compared with only fSRT. Thus, rAd-p53 combined with fractionated SRT may be preferred as a choice of local treatment for primary HCC when the patients are inoperable or when the patients refuse operation.

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    • "Small clinical trials with Ad-p53 have also been carried out in patients with hepatocellular cancer, ovarian cancer, esophageal cancer and gliomas (for review, see Refs. [96] [97]). Overall, the main conclusion from these trials is that Ad-p53 is relatively free of major toxicity but has limited efficacy. "
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    • "The E1-defective replication-incompetent adenoviral vectors used earlier are incapable of replication; the safety is guaranteed but the infection of each tumor cell is impossible, which limited its therapeutic effect. The world first anti-tumor gene therapeutic drug, recombinant human P53 adenovirus (Ad- P53), which was approved by the State Food and Drug Administration (SFDA) of China in 2004, belongs to this replicationincompetent adenoviral vector (Lu et al., 2011; Yang et al., 2010; Peng, 2005). More recently, the conditionally replicative adenovirus (CRAd), which can replicate specifically in tumor cells and can therefore infect, kill more tumor cells (also called oncolytic adenovirus) has been developed; the early representative of oncolytic adenovirus was Onyx-015 (Bagheri et al., 2011; Hemminki et al., 2011; He et al., 2009; Opyrchal et al., 2009). "
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    • "Despite remarkable examples of therapeutic efficacy in patients with Li-Fraumeni syndrome, an autosomal-dominant mutation of the p53 gene, the Food and Drug Administration (FDA) did not approve Advexin, the western version of a wt-p53-encoding adenovirus developed by Introgen Therapeutics. Nevertheless , the equivalent Gendicine, in combination with radiotherapy , is being applied in the treatment of head and neck cancer in China since several years and also shows efficacy in the combination treatment of hepatocellular carcinoma (Shi and Zheng, 2009; Yang et al., 2010). "
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    British Journal of Pharmacology 06/2011; 165(2):328-44. DOI:10.1111/j.1476-5381.2011.01570.x · 4.84 Impact Factor
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