This is the final part of a three-part discussion of Gendicine, a form of gene therapy currently undergoing clinical trials in China. The first two articles in this series can be accessed at:
http://www.cancerdecisions.com/061806.html
http://www.cancerdecisions.com/070906.html

Whether or not to travel to get an unapproved but promising-sounding treatment that is unavailable at home is always a complicated decision. Part of the decision certainly depends on obtaining an accurate evaluation of the likelihood of substantial and sustained benefit from the treatment in question. The figures coming out of China are undoubtedly very impressive. Dr. Peng claims that for more than three years after 12 patients with mid-to late-stage laryngeal cancer received Gendicine therapy (in phase 1 clinical trials), no patient had relapsed. By contrast, he says, among patients who received only surgery, the three-year relapse rate was approximately 30 percent (BioPharm 2004).

Another highly desirable feature of this treatment is that patients allegedly do not need to stay on the drug for the rest of their lives. Patients receive a single injection per week for four weeks. Each injection contains approximately one billion viral particles per dose. If patients respond, they are given another four consecutive weeks of treatment. This constitutes one treatment cycle. The Chinese researchers have found that if a patient does not respond after one month, he or she is very unlikely to respond to a further month of therapy.

Yet despite what seem to be promising early results, I have some questions about this treatment program. First, most valid treatments emerge from a rigorous peer-reviewed clinical trial system that, for all its shortcomings, serves to deter self-deception in science. But at present there are only six PubMed-listed articles on the topic of Gendicine. One of these is a report of a clinical trial - but it is in Chinese and contains only a brief English-language abstract and so it is presently unavailable to most Western readers. I can find no references to Gendicine at any of the past dozen years' meetings of the American Society for Clinical Oncology (ASCO), which is the major international professional forum in the cancer field.

The only non-Chinese scientific report in PubMed is by Siddhesh D. Patil, PhD, and colleagues at the University of Connecticut in Storrs, who state: "Clinical trials using Gendicine demonstrated complete regression of tumors in approximately two thirds of volunteers with late-stage head and neck squamous cell carcinoma" (Patil 2005). But this is a review article that is not citing new research.

Dr. Peng offered some greater detail in an informative 2004 report in BioPharm International. He said that 135 patients with late-stage head and neck squamous cell carcinoma (HNSCC) took part in phase II and III trials during the period from November 2000 to May 2003. (Three quarters of the patients suffered from advanced nasopharyngeal cancer.) The results showed complete regression of tumors in 64 percent of the patients after eight weekly injections of Gendicine in combination with radiation therapy; 29 percent of the patients experienced partial regression. Thus, there was some response in an astonishing 93 percent of the patients treated.

The treatment is generally given intratumorally - i.e., directly into the tumor - but when the disease is advanced and there are distant metastases, or when the tumor is located in an area that is difficult to reach with a needle, the treatment can in some instances be administered via an intravenous drip. Gendicine can also be administered via hepatic artery infusion, intraperitoneal injection, bronchoalveolar lavage, and (in the case of bladder cancer) via intravesical instillation.

"We find that in combination with chemo and radiotherapy," said Dr. Peng. "Gendicine can improve treatment efficacy by 3 to 4-fold. Furthermore, this combination not only improves treatment efficacy, but it also appears to alleviate the toxic side effects normally associated with chemotherapy and radiation therapy."

There is also a report in the literature of young patient with a recurrent hepatocellular carcinoma (HCC) who was given a combination of standard transcatheter arterial chemoembolization (TACE) into Gendicine injections into his liver lesions. After two months follow-up, he was declared in good clinical condition with normal liver function and no sign of recurrence (Guan 2005a and Guan 2005b).

However, some Western commentators have questioned the lack of rigorous data. "An extraordinary opportunity to have had a really big impact was lost," said Barry Carter, executive vice president of Seattle-based company Targeted Genetics. "You can't tell from the published data what the real trial design was, what the protocol was - and that's too bad" (Red 2006).

Others are willing to take the Chinese developments at face value. "The Chinese authorities have gotten ahead of the West," said Nigel Parker, CEO of Ark Therapeutics, a biotechnology firm working in this same field. "They've seen a lot more data, and they've seen the first approval, and I think it's going to be good for the field" (Red Herring 2006).

I hope to have the opportunity to go to China at some point in the future to study the development of Gendicine first hand. In the meantime, I urge readers to be careful consumers and to gather as much information as possible before opting to go to China for this unusual treatment.

--Ralph W. Moss, Ph.D.

Resources:

For information on treatment patients can call: +86-755-26980823 (From the US one needs to preface this number with the international dialing code, 011).

Referral email: A employee named Aiqi (pronounced Ay-see) speaks decent English. She can be reached at: This e-mail address is being protected from spam bots, you need JavaScript enabled to view it

For further information:

Dr.Zhaohui Peng
Chairman, CEO and founder,
Shenzhen SiBiono GeneTech Co.,Ltd.
Langshen Road,Shenzhen Hi-Tech Industrial Park
Shenzhen, China
Tel: 0755.2696.8818
Fax: 0755.2696.8808 or 86-755-2698-0872
Email: This e-mail address is being protected from spam bots, you need JavaScript enabled to view it
Web: www.sibiono.com.

References:

BioPharm International:
http://www.nbsc.com/files/papers/BP5-08-04Ae.pdf

George, S. L. (2003). Selection bias, phase II trials, and the FDA accelerated approval process. J Natl Cancer Inst 95: 1351-1352

Guan YS, Liu Y, Sun L, Li X, He Q. Successful management of postoperative recurrence of hepatocellular carcinoma with p53 gene therapy combining transcatheter arterial chemoembolization. World J Gastroenterol. 2005 Jun 28;11(24):3803-5.

Guan YS, Liu Y, Zhou XP, Li X, He Q, Sun L. p53 gene (Gendicine) and embolisation overcame recurrent hepatocellular carcinoma. Gut. 2005 Sep;54(9):1318-9. Epub 2005 May 5.

Jim Lehrer report on gene therapy:
http://www.pbs.org/newshour/bb/health/jan-june00/gene_therapy_2-2.html

Kirchweger, Gina. Mouse study reveals human X-SCID gene therapy poses substantial cancer risk. Salk Institute Press Release, April 26, 2006. Available at:
http://www.eurekalert.org/pub_releases/2006-04/si-msr042106.php

Moss, Ralph W. Questioning Chemotherapy. State College: Equinox Press, 2000. To order go to:
http://www.cancerdecisions.com/books.html

Patil SD, Rhodes DG, Burgess DJ. DNA-based therapeutics and DNA delivery systems: a comprehensive review. AAPS J. 2005 Apr 8;7(1):E61-77. Review.

Pogge RC. The toxic placebo, I: side and toxic effects reported during the administration of placebo medicine. Med Times. 1963,91:14.

Red Herring article:
http://www.redherring.com/Article.aspx?a=16613&hed=China’s+War+on+Cancer

Salk Institute findings:
http://www.medicalnewstoday.com/medicalnews.php?newsid=42339

Zhang SW, Zhao M, Xiao SW, et al., Detection of p53 gene change and serum antibody level in phase II clinical trial of ad p53 gene therapy. Zhonghua Yi Xue Za Zhi. 2005 Dec 28;85(49):3495-8.