title: Safety evaluation of high-dose BCNU-loaded biodegradable implants in Chinese patients with recurrent malignant gliomas.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Adults with supratentorial recurrent malignant glioma were eligible. High-dose BCNU-loaded PLGA implants (20mg 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.
authors.affiliation: 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. Electronic address: saike@sysucc.org.cn.
authors.forename: Ke
authors.initials: K
authors.lastname: Sai
authors.affiliation: 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. Electronic address: 35goodluck@gmail.com.
authors.forename: Ming-Gu
authors.initials: MG
authors.lastname: Zhong
authors.affiliation: 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. Electronic address: wangjian2@sysucc.org.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: 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. Electronic address: chenyinsh@sysucc.org.cn.
authors.forename: Yin-Sheng
authors.initials: YS
authors.lastname: Chen
authors.affiliation: 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. Electronic address: mouyg@sysucc.org.cn.
authors.forename: Yong-Gao
authors.initials: YG
authors.lastname: Mou
authors.affiliation: 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. Electronic address: kechao@sysucc.org.cn.
authors.forename: Chao
authors.initials: C
authors.lastname: Ke
authors.affiliation: 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. Electronic address: zhangxh@sysucc.org.cn.
authors.forename: Xiang-Heng
authors.initials: XH
authors.lastname: Zhang
authors.affiliation: 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. Electronic address: yangqy@sysucc.org.cn.
authors.forename: Qun-Ying
authors.initials: QY
authors.lastname: Yang
authors.affiliation: 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. Electronic address: linfuh@sysucc.org.cn.
authors.forename: Fu-Hua
authors.initials: FH
authors.lastname: Lin
authors.affiliation: 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. Electronic address: guochch@sysucc.org.cn.
authors.forename: Cheng-Cheng
authors.initials: CC
authors.lastname: Guo
authors.affiliation: 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. Electronic address: chenzhengh@sysucc.org.cn.
authors.forename: Zheng-He
authors.initials: ZH
authors.lastname: Chen
authors.affiliation: 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. Electronic address: zengjing@sysucc.org.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Zeng
authors.affiliation: 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. Electronic address: lvych@sysucc.org.cn.
authors.forename: Yan-Chun
authors.initials: YC
authors.lastname: Lv
authors.affiliation: Department of Neurosurgery, Xuzhou Medical College Hospital, 99 West Huaihai Road, Xuzhou 221000, China. Electronic address: jixiangbull@126.com.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Xuzhou Medical College Hospital, 99 West Huaihai Road, Xuzhou 221000, China. Electronic address: gaowc_xuzhou@tom.com.
authors.forename: Wen-Chang
authors.initials: WC
authors.lastname: Gao
authors.affiliation: 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. Electronic address: chenzp57@mail.sysu.edu.cn.
authors.forename: Zhong-Ping
authors.initials: ZP
authors.lastname: Chen
mesh_terms: D020341:Absorbable Implants; D000293:Adolescent; D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000493:pharmacokinetics / Q000627:therapeutic use*; D044466:Asian People; D001932:Brain Neoplasms / Q000188:drug therapy*; D002330:Carmustine / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003652:Decanoic Acids / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D017567:Karnofsky Performance Status; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D011091:Polyesters / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003652:Decanoic Acids; D011091:Polyesters; C574855:carmustine, poliferprosan 20 drug combination; D002330:Carmustine
keywords: BCNU; Biodegradable polymer; Clinical trial; Interstitial chemotherapy; Malignant glioma; Safety