title: Phase I/II dose-finding study of nanoparticle albumin-bound paclitaxel (nab®-Paclitaxel) plus Cisplatin as Treatment for Metastatic Nasopharyngeal Carcinoma.
abstract: This phase I/II study aimed to determine the maximum tolerated dose (MTD) of nanoparticle albumin-bound paclitaxel (nab (®)-paclitaxel) plus cisplatin as treatment for metastatic nasopharyngeal carcinoma (NPC).
  
  
  
  Patients were enrolled into 1 of 3 dose cohorts, each with 21-day treatment cycles: 1) intravenous (IV) nab-paclitaxel 260 mg/m(2) on day 1; 2) IV nab-paclitaxel 140 mg/m(2) on days 1 and 8; 3) IV nab-paclitaxel 100 mg/m(2) on days 1, 8, and 15. All patients received IV cisplatin 75 mg/m(2) on day 1. Treatment continued for 4-6 cycles, or until progression or unacceptable toxicity. If more than one-third of the patients in a cohort experienced a dose-limiting toxicity (DLT), the dose used in the previous cohort would be designated the MTD. Secreted protein acidic and rich in cysteine (SPARC) expression was detected by immunohistochemistry staining.
  
  
  
  Sixty-nine patients were enrolled, of whom 64 and 67 were eligible for efficacy and safety analysis, respectively. Two DLTs occurred in cohort 1 (grade 4 febrile neutropenia, grade 3 myalgia), none occurred in cohort 2, and 2 occurred in cohort 3 (both grade 3 fatigue). The MTD was not reached. Partial responses were achieved by 42 patients, 15 had stable disease, and 7 had progressive disease, giving an overall response rate of 66 %. Median progression-free survival was 9 months (95 % CI, 6-12 months). Grade ≥ 3 adverse events were mainly hematologic. There was no significant difference between the 3 cohorts with respect to efficacy or safety. Biomarker analyses indicated that stromal, rather than tumoral, SPARC may predict the response to nab-paclitaxel in NPC.
  
  
  
  Our findings suggest that nab-paclitaxel plus cisplatin is a highly active regimen with moderate toxicity for the treatment of metastatic NPC, which warrants further investigation in a phase III study.
  
  
  
  ClinicalTrials.gov ID: NCT01735409 . The trial was registered on November 20th, 2012.
authors.affiliation: Sun Yat-sen University Cancer Center, Yuexiu, Guangzhou, China.|State Key Laboratory of Oncology in South China, Guangzhou, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Sun Yat-sen University Cancer Center, Yuexiu, Guangzhou, China.|State Key Laboratory of Oncology in South China, Guangzhou, China.|The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Liang
authors.affiliation: Sun Yat-sen University Cancer Center, Yuexiu, Guangzhou, China.|State Key Laboratory of Oncology in South China, Guangzhou, China.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Sun Yat-sen University Cancer Center, Yuexiu, Guangzhou, China.|State Key Laboratory of Oncology in South China, Guangzhou, China.|Shaoguan Yuebei People Hospital, Shaoguan, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Sun Yat-sen University Cancer Center, Yuexiu, Guangzhou, China.|State Key Laboratory of Oncology in South China, Guangzhou, China.
authors.forename: Hongyun
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Sun Yat-sen University Cancer Center, Yuexiu, Guangzhou, China.|State Key Laboratory of Oncology in South China, Guangzhou, China.|Shenzhen Hospital of Peking Univeristy, Shenzhen, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Wu
authors.affiliation: Sun Yat-sen University Cancer Center, Yuexiu, Guangzhou, China.|State Key Laboratory of Oncology in South China, Guangzhou, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Sun Yat-sen University Cancer Center, Yuexiu, Guangzhou, China.|State Key Laboratory of Oncology in South China, Guangzhou, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Sun Yat-sen University Cancer Center, Yuexiu, Guangzhou, China. zhangli6@mail.sysu.edu.cn.|State Key Laboratory of Oncology in South China, Guangzhou, China. zhangli6@mail.sysu.edu.cn.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. zhangli6@mail.sysu.edu.cn.|Department of Medical Oncology, Cancer Center, Sun Yat-Sen University, 651 Dongfeng Road, East, Guangzhou, 510060, People's Republic of China. zhangli6@mail.sysu.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000068196:Albumin-Bound Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000418:Albumins / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D002277:Carcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015676:Osteonectin / Q000378:metabolism*; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: C520255:130-nm albumin-bound paclitaxel; D000068196:Albumin-Bound Paclitaxel; D000418:Albumins; D015676:Osteonectin; C577241:SPARC protein, human; D017239:Paclitaxel; D002945:Cisplatin