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Safety evaluation of high-dose BCNU-loaded biodegradable implants in Chinese patients with recurrent malignant gliomas

  • Author Footnotes
    1 These two authors contributed equally to the manuscript.
    Ke Sai
    Footnotes
    1 These two authors contributed equally to the manuscript.
    Affiliations
    Department of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China

    Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou 510060, China

    State Key Laboratory of Oncology in South China, 651 Dongfeng Road East, Guangzhou 510060, China
    Search for articles by this author
  • Author Footnotes
    1 These two authors contributed equally to the manuscript.
    ,
    Author Footnotes
    2 Present address: Department of Neurosurgery, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-sen University, 23 Haibang Street, Jiangmen 529030, China.
    Ming-gu Zhong
    Footnotes
    1 These two authors contributed equally to the manuscript.
    2 Present address: Department of Neurosurgery, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-sen University, 23 Haibang Street, Jiangmen 529030, China.
    Affiliations
    Department of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China

    Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou 510060, China

    State Key Laboratory of Oncology in South China, 651 Dongfeng Road East, Guangzhou 510060, China
    Search for articles by this author
  • Jian Wang
    Affiliations
    Department of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China

    Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou 510060, China

    State Key Laboratory of Oncology in South China, 651 Dongfeng Road East, Guangzhou 510060, China
    Search for articles by this author
  • Yin-sheng Chen
    Affiliations
    Department of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China

    Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou 510060, China

    State Key Laboratory of Oncology in South China, 651 Dongfeng Road East, Guangzhou 510060, China
    Search for articles by this author
  • Yong-gao Mou
    Affiliations
    Department of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China

    Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou 510060, China

    State Key Laboratory of Oncology in South China, 651 Dongfeng Road East, Guangzhou 510060, China
    Search for articles by this author
  • Chao Ke
    Affiliations
    Department of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China

    Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou 510060, China

    State Key Laboratory of Oncology in South China, 651 Dongfeng Road East, Guangzhou 510060, China
    Search for articles by this author
  • Xiang-heng Zhang
    Affiliations
    Department of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China

    Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou 510060, China

    State Key Laboratory of Oncology in South China, 651 Dongfeng Road East, Guangzhou 510060, China
    Search for articles by this author
  • Qun-ying Yang
    Affiliations
    Department of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China

    Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou 510060, China

    State Key Laboratory of Oncology in South China, 651 Dongfeng Road East, Guangzhou 510060, China
    Search for articles by this author
  • Fu-hua Lin
    Affiliations
    Department of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China

    Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou 510060, China

    State Key Laboratory of Oncology in South China, 651 Dongfeng Road East, Guangzhou 510060, China
    Search for articles by this author
  • Cheng-cheng Guo
    Affiliations
    Department of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China

    Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou 510060, China

    State Key Laboratory of Oncology in South China, 651 Dongfeng Road East, Guangzhou 510060, China
    Search for articles by this author
  • Zheng-he Chen
    Affiliations
    Department of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China

    Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou 510060, China

    State Key Laboratory of Oncology in South China, 651 Dongfeng Road East, Guangzhou 510060, China
    Search for articles by this author
  • Jing Zeng
    Affiliations
    Department of Pathology, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China

    Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou 510060, China

    State Key Laboratory of Oncology in South China, 651 Dongfeng Road East, Guangzhou 510060, China
    Search for articles by this author
  • Yan-chun Lv
    Affiliations
    Department of Imaging and Minimally Invasive Interventional Center, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China

    Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou 510060, China

    State Key Laboratory of Oncology in South China, 651 Dongfeng Road East, Guangzhou 510060, China
    Search for articles by this author
  • Xiang Li
    Affiliations
    Department of Neurosurgery, Xuzhou Medical College Hospital, 99 West Huaihai Road, Xuzhou 221000, China
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  • Wen-chang Gao
    Affiliations
    Department of Neurosurgery, Xuzhou Medical College Hospital, 99 West Huaihai Road, Xuzhou 221000, China
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  • Zhong-ping Chen
    Correspondence
    Corresponding author at: Department of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China. Tel./fax: +86 20 87343310.
    Affiliations
    Department of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China

    Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou 510060, China

    State Key Laboratory of Oncology in South China, 651 Dongfeng Road East, Guangzhou 510060, China
    Search for articles by this author
  • Author Footnotes
    1 These two authors contributed equally to the manuscript.
    2 Present address: Department of Neurosurgery, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-sen University, 23 Haibang Street, Jiangmen 529030, China.

      Highlights

      • We assess the safety of high-dose BCNU-loaded PLGA implants in Chinese patients.
      • Subgaleal effusion is the most common adverse event.
      • BCNU-loaded PLGA implants are well tolerated in Chinese patients.
      • The OS of the cohort of patients is longer than that of historical control.

      Abstract

      Objectives

      Malignant gliomas are common primary brain tumors with dismal prognosis. The blood–brain barrier and unacceptable systemic toxicity limit the employment of chemotherapeutic agents. BCNU-impregnated biodegradable polymers (Gliadel®) have been demonstrated to prolong the survival of patients with malignant gliomas. Until now, no biodegradable drug delivery system has been commercially available in China. In the present study, we evaluated the safety of implants with high-dose BCNU in Chinese patients with recurrent malignant gliomas.

      Patients and methods

      Adults with supratentorial recurrent malignant glioma were eligible. High-dose BCNU-loaded PLGA implants (20 mg of BCNU in each implant) were placed in the debulking cavity. The implants were investigated by a classical 3 + 3 design. Four levels of BCNU, up to 12 implants, were evaluated. Pharmacokinetic sampling was performed. The toxicity of the implants and the survival of patients were recorded.

      Results

      Fifteen recurrent patients were enrolled with 12 glioblastomas and 3 anaplastic gliomas. Among 15 patients, 3 were treated with 3 implants (60 mg of BCNU), 3 with 6 implants (120 mg), 3 with 9 implants (180 mg) and 6 with 12 implants (240 mg). No dose-limiting toxicity was observed in the cohort of patients. Subgaleal effusion was the most common adverse event, presenting in 7 patients (46.7%). The median overall survival (OS) was 322 days (95% CI, 173–471 days). The 6-month, 1-year and 2-year survival rates were 66.7%, 40% and 13.3%, respectively.

      Conclusions

      The high-dose BCNU-loaded PLGA implants were safe for Chinese patients with recurrent malignant gliomas and further investigation for efficacy is warranted.

      Keywords

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