Original Articles

Chinese Journal of Clinical Oncology

, Volume 2, Issue 4, pp 706-716

Phase III clinical trials of the cell differentiation agent-2 (CDA-2): Therapeutic efficacy on breast cancer, non-small cell lung cancer and primary hepatoma1

  • Fengyi FengAffiliated withThe Cancer Hospital of the Chinese Academy of Medical Science
  • , Qing LiAffiliated withThe Cancer Hospital of the Chinese Academy of Medical Science
  • , Changquan LingAffiliated withChanghai Hospital of the Second Army Medical University
  • , Yang ZhangAffiliated withThe Second Affiliated Hospital of Dalian Medical University
  • , Fengzhan QinAffiliated withThe Cancer Hospital of Bengbu Medical College
  • , Huaqing WangAffiliated withThe Cancer Hospital of Tianjin Medical University
  • , Wenxia HuangAffiliated withThe Affiliated Cancer Hospital of Fudan Medical University
  • , Shunchang JiaoAffiliated withThe General Hospitalof PLA
  • , Qiang ChenAffiliated withThe Cancer Hospital of Fujian Province
    • , Mingzhong LiAffiliated withThe First Affiliated Hospital of Xi’an Communication University
    • , Yunzhong ZhuAffiliated withThe Cancer Hospital of the Chinese Academy of Medical ScienceBeijing Chest Cancer Hospital
    • , Meizhen ZhouAffiliated withThe Cancer Hospital of the Chinese Academy of Medical ScienceDepartment of Health Beijing Hospital
    • , Jun RenAffiliated withThe Cancer Hospital of the Chinese Academy of Medical ScienceXijing Hospital of the Fourth Military Medical University
    • , Yetao GaoAffiliated withChanghai Hospital of the Second Army Medical University
    • , Jingpo ZhaoAffiliated withThe Second Affiliated Hospital of Dalian Medical University
    • , Rongsheng ZhengAffiliated withThe Cancer Hospital of Bengbu Medical College
    • , Wenhua ZhaoAffiliated withThe Cancer Hospital of Tianjin Medical University
    • , Zhiqiang MengAffiliated withThe Affiliated Cancer Hospital of Fudan Medical University
    • , Fang LiAffiliated withThe General Hospitalof PLA
    • , Qizhong ZhangAffiliated withThe Cancer Hospital of Fujian Province
    • , Dongli ZhaoAffiliated withThe First Affiliated Hospital of Xi’an Communication University
    • , Liyan XuAffiliated withThe Cancer Hospital of the Chinese Academy of Medical ScienceBeijing Chest Cancer Hospital
    • , Yongqiang ZhangAffiliated withThe Cancer Hospital of the Chinese Academy of Medical ScienceDepartment of Health Beijing Hospital
    • , Yanjun ZhangAffiliated withThe Cancer Hospital of the Chinese Academy of Medical ScienceXijing Hospital of the Fourth Military Medical University
    • , Zhenjiu WangAffiliated withThe Cancer Hospital of the Chinese Academy of Medical ScienceEverlife Pharmaceutical Company
    • , Shuanqi LiuAffiliated withThe Cancer Hospital of the Chinese Academy of Medical ScienceEverlife Pharmaceutical Company
    • , Ming C. LiauAffiliated withThe Cancer Hospital of the Chinese Academy of Medical ScienceInstitute of Pharmaceutical Chemistry, China Medical University

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Abstract

Objective

The objective of this study was to explore the effect of CDA-2, a selective inhibitor of abnormal methylation enzymes in cancer cells, on the therapeutic efficacy of cytotoxic chemotherapy.

Methods

Advanced cancer patients, all of whom had previously undergone chemotherapy, were randomly divided into 2 groups, one receiving chemotherapy only as the control group, and the other receiving CDA-2 in addition to chemotherapy as the combination group. The therapeutic efficacies and the toxic manifestations of the 2 groups were compared based on the WHO criteria.

Results

Of 454 cancer patients enrolled in phase III clinical trials of CDA-2, 80, 188, and 186 were breast cancer, NSCLC, and primary hepatoma patients, respectively. Among them 378 patients completed treatments according to the protocols. The results showed that the overall effective rate of the combination group was 2.6 fold that of the control group, 4.8 fold in the case of breast cancer, 2.3 fold in the case of primary hepatoma, and 2.2 fold in the case of NSCLC. Surprisingly, the combination therapy appeared to work better for stage IV than stage III patients. CDA-2 did not contribute additional toxicity. On the contrary, it reduced toxic manifestations of chemotherapy, particularly regarding white blood cells, nausea and vomiting.

Conclusion

Modulation of abnormal methylation enzymes by CDA-2 is definitely helpful to supplement chemotherapy. It significantly increased the therapeutic efficacy and reduced the toxic manifestation of cytotoxic chemotherapy on breast cancer and NSCLC.

Keywords

abnormal methylation enzymes DNA hypomethylation differentiation therapy adjuvant chemotherapy