title: A Phase II study of pazopanib in Asian patients with recurrent/metastatic nasopharyngeal carcinoma.
abstract: OBJECTIVE
  Nasopharyngeal carcinoma is endemic in Asia and angiogenesis is important for growth and progression. We hypothesized that pazopanib would have antiangiogenic activity in nasopharyngeal carcinoma.
  
  
  METHODS
  A single arm monotherapy study of pazopanib in patients with WHO type II/III nasopharyngeal carcinoma who had metastatic/recurrent disease and failed at least one line of chemotherapy. A Simon's optimal 2-stage design was used. Patients with Eastern Cooperative Oncology Group (ECOG) 0-2 and adequate organ function were treated with pazopanib 800 mg daily on a 21-day cycle. The primary endpoint was clinical benefit rate (CR/PR/SD) achieved after 12 weeks of treatment. Secondary endpoints included toxicity and progression-free survival. Exploratory studies of dynamic-contrast enhanced computed tomography (DCE-CT) paired with pharmacokinetics (PK) of pazopanib was done.
  
  
  RESULTS
  Thirty-three patients were accrued. Patients were ECOG 0-1 with median age of 50 years (range 36-68). There were 2 (6.1%) partial responses, 16 (48.5%) stable disease, 11 (33.3%) progressive disease, 4 (12.1%) were not evaluable for response. The clinical benefit rate was 54.5% (95% CI: 38.0-70.2). Ten patients (30.3%) received more than 6 cycles (4 months) of treatment and 7 (21.2%) had PR/SD that lasted at least 6 months. One patient each died from epistaxis and myocardial infarction. Common grade 3/4 toxicities included fatigue (15.2%), hand-foot syndrome (15.2%), anorexia (9.1%), diarrhea (6.1%), and vomiting (6.1%). Serial DCE-CT scans show significant reductions in tumor blood flow, permeability surface area product, and fractional intravascular blood volume.
  
  
  CONCLUSIONS
  Pazopanib showed encouraging activity in heavily pretreated nasopharyngeal carcinoma with an acceptable toxicity profile.
authors.affiliation: Department of Medical Oncology, National Cancer Centre Singapore, Singapore. dmolwt@nccs.com.sg
authors.forename: Wan-Teck
authors.initials: WT
authors.lastname: Lim
authors.forename: Quan-Sing
authors.initials: QS
authors.lastname: Ng
authors.forename: Percy
authors.initials: P
authors.lastname: Ivy
authors.forename: Swan-Swan
authors.initials: SS
authors.lastname: Leong
authors.forename: Onkar
authors.initials: O
authors.lastname: Singh
authors.forename: Balram
authors.initials: B
authors.lastname: Chowbay
authors.forename: Fei
authors.initials: F
authors.lastname: Gao
authors.forename: Choon Hua
authors.initials: CH
authors.lastname: Thng
authors.forename: Boon-Cher
authors.initials: BC
authors.lastname: Goh
authors.forename: Daniel Shao-Weng
authors.initials: DS
authors.lastname: Tan
authors.forename: Tong San
authors.initials: TS
authors.lastname: Koh
authors.forename: Chee-Keong
authors.initials: CK
authors.lastname: Toh
authors.forename: Eng-Huat
authors.initials: EH
authors.lastname: Tan
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D000855:Anorexia / Q000139:chemically induced; D044466:Asian People; D002277:Carcinoma; D003967:Diarrhea / Q000139:chemically induced; D004334:Drug Administration Schedule; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006801:Humans; D007191:Indazoles; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000208:ethnology / Q000473:pathology; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D009389:Neovascularization, Pathologic / Q000208:ethnology / Q000378:metabolism / Q000517:prevention & control; D011743:Pyrimidines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013449:Sulfonamides / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced
chemical_list: D020533:Angiogenesis Inhibitors; D007191:Indazoles; D011743:Pyrimidines; D013449:Sulfonamides; C516667:pazopanib