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Journal of Zhejiang University SCIENCE B 2009 Vol.10 No.5 P.331~340


Adenovirus-mediated wild-type p53 gene transfer in combination with bronchial arterial infusion for treatment of advanced non-small-cell lung cancer, one year follow-up

Author(s):  Yong-song GUAN, Yuan LIU, Qing ZOU, Qing HE, Zi LA, Lin YANG, Ying HU

Affiliation(s):  Department of Oncology, West China Hospital of Sichuan University, Chengdu 610041, China; more

Corresponding email(s):   YongsongGuan@yahoo.com

Key Words:  RAd-p53 gene therapy, Clinical trial, Non-small-cell lung cancer (NSCLC), Bronchial arterial infusion (BAI)

Yong-song GUAN, Yuan LIU, Qing ZOU, Qing HE, Zi LA, Lin YANG, Ying HU. Adenovirus-mediated wild-type p53 gene transfer in combination with bronchial arterial infusion for treatment of advanced non-small-cell lung cancer, one year follow-up[J]. Journal of Zhejiang University Science B, 2009, 10(5): 331~340.

@article{title="Adenovirus-mediated wild-type p53 gene transfer in combination with bronchial arterial infusion for treatment of advanced non-small-cell lung cancer, one year follow-up",
author="Yong-song GUAN, Yuan LIU, Qing ZOU, Qing HE, Zi LA, Lin YANG, Ying HU",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Adenovirus-mediated wild-type p53 gene transfer in combination with bronchial arterial infusion for treatment of advanced non-small-cell lung cancer, one year follow-up
%A Yong-song GUAN
%A Yuan LIU
%A Qing ZOU
%A Qing HE
%A Zi LA
%A Ying HU
%J Journal of Zhejiang University SCIENCE B
%V 10
%N 5
%P 331~340
%@ 1673-1581
%D 2009
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B0820248

T1 - Adenovirus-mediated wild-type p53 gene transfer in combination with bronchial arterial infusion for treatment of advanced non-small-cell lung cancer, one year follow-up
A1 - Yong-song GUAN
A1 - Yuan LIU
A1 - Qing ZOU
A1 - Qing HE
A1 - Zi LA
A1 - Lin YANG
A1 - Ying HU
J0 - Journal of Zhejiang University Science B
VL - 10
IS - 5
SP - 331
EP - 340
%@ 1673-1581
Y1 - 2009
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B0820248

Objective: In the present study, we have examined the safety and efficacy of recombinant adenovirus encoding human p53 tumor suppressor gene (rAd-p53) injection in patients with advanced non-small-cell lung cancer (NSCLC) in the combination with the therapy of bronchial arterial infusion (BAI). Methods: A total of 58 patients with advanced NSCLC were enrolled in a non-randomized, two-armed clinical trial. Of which, 19 received a combination treatment of BAI and rAd-p53 (the combo group), while the remaining 39 were treated with only BAI (the control group). Patients were followed up for 12 months, with safety and local response evaluated by the National Cancer Institute’s Common Toxicity Criteria and response evaluation criteria in solid tumor (RECIST), respectively. Time to progression (TTP) and survival rates were also analyzed by Kaplan-Meier method. Results: In the combo group, 19 patients received a total of 49 injections of rAd-p53 and 46 times of BAI, respectively, while 39 patients in the control group received a total of 113 times of BAI. The combination treatment was found to have less adverse events such as anorexia, nausea and emesis, pain, and leucopenia (P<0.05) but more arthralgia, fever, influenza-like symptom, and myalgia (P<0.05), compared with the control group. The overall response rates (complete response (CR)+partial response (PR)) were 47.3% and 38.4% for the combo group and the control group, respectively (P>0.05). Patients in the combo group had a longer TTP than those in the control group (a median 7.75 vs 5.5 months, P=0.018). However, the combination treatment did not lead to better survival, with survival rates at 3, 6, and 12 months in the combo group being 94.74%, 89.47%, and 52.63%, respectively, compared with 92.31%, 69.23%, and 38.83% in the control group (P=0.224). Conclusion: Our results show that the combination of rAd-p53 and BAI was well tolerated in patients with NSCLC and may have improved the quality of life and delayed the disease progression. A further study to better determine the efficacy of this combination therapy is warranted.

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1] Ajani, J.A., Welch, S.R., Raber, M.N., 1990. Comprehensive criteria for assessing therapy-induced toxicity. Cancer Invest., 8(2):147-159.

[2] Bauer, J.H., Helfand, S.L., 2006. New tricks of an old molecule: lifespan regulation by p53. Aging Cell, 5(5): 437-440.

[3] Chen, C.B., Pan, J.J., Xu, L.Y., 2003. Recombinant adenovirus-p53 agent injection combine with radiotherapy in treatment of nasopharyngeal carcinoma: a phase. II. Clinical trial. Zhonghua Yi Xue Za Zhi, 83(23):2033-2035 (in Chinese).

[4] Daniel, J.C., Smythe, W.R., 2003. Gene therapy of lung cancer. Semin. Surg. Oncol., 21(3):196-204.

[5] Frasci, G., Panza, N., Comella, G., Pcillio, G., 1999. Is there any impact of new drugs on the outcome of advanced NSCLC? An overview of the Southern Italy Cooperative Oncology Group trials. Oncologist, 4(5):379-385.

[6] Guan, Y.S., Liu, Y., Zhou, X.P., Li, X., He, Q., Sun, L., 2005. p53 gene (Gendicine) and embolization overcame recurrent hepatocellular carcinoma. Gut, 54(9):1318-1319.

[7] Hollstein, M., Rice, K., Greenblatt, M.S., Soussi, T., Fuchs, R., S(rlie, T., Hovig, E., Smith-s(rensen, B., Montesano, R., Harris, C.C., 1994. Database of p53 gene somatic mutations in human tumors and cell lines. Nucleic Acids Res., 22(17):3551-3555.

[8] Inoue, A., Natumi, K., Matsubrara, N., Sugawara, S., Saijo, Y., Satoh, K., Nukiwa, T., 2000. Administration of wild-type p53 adenoviral vector synergistically enhances the cytotoxicity of anti-cancer drugs in human lung cancer cells irrespective of the status of p53 gene. Cancer Lett., 157(1):105-112.

[9] Junker, K., Wiethege, T., Muller, K.M., Thomas, M., 2000. p53 tumour-suppressor gene in non-small-cell lung cancer with neoadjuvant therapy. J. Cancer Res. Clin. Oncol., 126(4):238-245.

[10] Kauczor, H.U., Schuler, M., Heussel, C.P., von Weymarn, A., Bongartz, G., Rochlitz, C., Huber, C., Thelen, M., 1999. CT-guided intratumoral gene therapy in non-small-cell lung cancer. Eur. Radiol., 9(2):292-296.

[11] Kawabe, S., Munshi, A., Zumstein, L.A., Wilson, D.R., Roth, J.A., Meyn, R.E., 2001. Adenovirus-mediated wild-type p53 gene expression radiosensitizes non-small cell lung cancer cells but not normal lung fibroblasts. Int. J. Radiat. Biol., 77(2):185-194.

[12] Ko, D., Hawkins, L., Yu, D.C., 2005. Development of transcriptionally regulated oncolytic adenoviruses. Oncogene, 24(52):7763-7774.

[13] Le Chevalier, T., Arriagada, R., Quoix, E., 1991. Radiotherapy alone versus combined chemotherapy and radiotherapy in non-resectable non-small cell lung cancer: first analysis of a randomized trial in 353 patients. J. Natl. Cancer Inst., 83(6):417-423.

[14] Levine, A.J., 1997. p53 the cellular gatekeeper for growth and division. Cell, 88(3):323-331.

[15] Lowe, S.W., 1995. Cancer gene therapy and p53. Curr. Opin. Oncol., 7(6):547-553.

[16] Moon, C., Oh, Y., Roth, J.A., 2003. Current status of gene therapy for lung cancer and head and neck cancer. Clin. Cancer Res., 9(14):5055-5067.

[17] Nemunaitis, J., Swisher, S.G., Timmons, T., Connors, D., Mack, M., Doerksen, L., Weill, D., Wait, J., Lawrence, D.D., Kemp, B.L., et al., 2000. Adenovirus-mediated p53 gene transfer in sequence with cisplatin to tumors of patients with non-small-cell lung cancer. J. Clin. Oncol., 18(3):609-622.

[18] Nishizaki, M., Meyn, R.E., Levy, L.B., Atkinson, E.N., White, R.A., Roth, J.A., Ji, L., 2001. Synergistic inhibition of human lung cancer cell growth by adenovirus-mediated wild-type p53 gene transfer in combination with docetaxel and radiation therapeutic in vitro and in vivo. Clin. Cancer Res., 7(9):2887-2897.

[19] Osaki, S., Nakanishi, Y., Takayama, K., Pei, X.H., Ueno, H., Hara, N., 2000. Alteration of drug chemosensitivity caused by the adenovirus-mediated transfer of the wild-type p53 gene in human lung cancer cells. Cancer Gene Ther., 7(2):300-307.

[20] Parker, S.L., Tong, T., Bolden, S., Wingo, P.A., 1997. Cancer statistics, 1997. CA Cancer J. Clin., 47(1):5-27.

[21] Peng, Z., 2005. Current status of gendicine in China: recombinant human Ad-p53 agent for treatment of cancers. Hum. Gene. Ther., 16(9):1016-1027.

[22] Roth, J.A., Nguyen, D., Lawrence, D.D., Kemp, B.L., Carrasco, C.H., Ferson, D.Z., Hong, W.K., Komaki, R., Lee, J.J., Nesbitt, J.C., et al., 1996. Retrovirus-mediated p53 gene therapy. Nat. Med., 2(9):985-991.

[23] Schaake-koning, C., van den Boggert, W., Dalesio, O., Festen, J., Hoogenhout, J., van Houtte, P., Kirpatrick, A., Koolen, M., Maat, B., Nijs, A., 1992. Effects of concomitant cisplatin and radiotherapy on inoperable non-small cell lung cancer. N. Engl. J. Med., 326(8):524-530.

[24] Schuler, M., Herrmann, R., de Greve, J.L., Stewart, A.K., Gatzemeier, U., Stewart, D.J., Laufman, L., Gralla, R., Kuball, J., Buhl, R., et al., 2001. Adenovirus-mediated wild-type p53 gene transfer in patients receiving chemotherapy for advanced non-small-cell lung cancer: results of a multicenter phase II study. J. Clin. Oncol., 19(6): 1750-1758.

[25] Swisher, S.G., Roth, J.A., 2002. Clinical update of Ad-p53 gene therapy for lung cancer. Surg. Oncol. Clin. N. Am., 11(3):521-535.

[26] Swisher, S.G., Roth, J.A., Nemunaitis, J., Lawrence, D.D., Kemp, B.L., Carrasco, C.H., Connors, D.G., El-naggar, A.K., Fossella, F., Glisson, B.S., et al., 1999. Adenovirus-mediated p53 gene transfer in advanced non-small-cell lung cancer. J. Natl. Cancer Inst., 91(9): 763-771.

[27] Swisher, S.G., Roth, J.A., Komaki, R., Gu, J., Lee, J.J., Hicks, M., Ro, J.Y., Hong, W.K., Merritt, J.A., Ahrar, K., et al., 2003. Induction of p53-regulated genes and tumor regression in ling cancer patients after intratumoral delivery of adenoviral p53 (INGN 201) and radiation therapy. Clin. Cancer Res., 9(1):93-101.

[28] Takahashi, T., Nau, M.M., Chiba, I., Birrer, M.J., Rosenberg, R.K., Vinocour, M., Levitt, M., Pass, H., Gazadr, A.F., Minna, J.D., 1989. p53: a frequent target for genetic abnormalities in lung cancer. Science, 246(4929):491-499.

[29] Therasse, P., Arbuck, S.G., Eisenhauer, E.A., Wanders, J., Kaplan, R.S., Rubinstein, L., Verweij, J., van Glabbeke, M., van Oostrom, A.T., Christian, M.C., Gwyther, S.G., 2000. New guidelines to evaluate the response to treatment in solid tumor. J. Natl. Cancer Inst., 92(3):205-216.

[30] Vogelstein, B., Kinzler, K.W., 1995. Through the glass lightly. Science, 267(5204):1613.

[31] Wang, G., Song, M., Xu, H., Fang, Y., 1996. Prospective trial of combined hyperfractionated radiotherapy and bronchial arterial infusion of chemotherapy for locally advanced non-small cell lung cancer. Int. J. Radiat Oncol. Biol. Phys., 34(2):309-313.

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