title: Metronomic adjuvant chemotherapy improves treatment outcome in nasopharyngeal carcinoma patients with postradiation persistently detectable plasma Epstein-Barr virus deoxyribonucleic acid.
abstract: OBJECTIVE
  To investigate the effects of adjuvant chemotherapy in nasopharyngeal carcinoma (NPC) patients with persistently detectable plasma Epstein-Barr virus DNA (pEBV DNA) after curative radiation therapy plus induction/concurrent chemotherapy.
  
  
  METHODS
  The study population consisted of 625 NPC patients with available pEBV DNA levels before and after treatment. Eighty-five patients with persistently detectable pEBV DNA after 1 week of completing radiation therapy were eligible for this retrospective study. Of the 85 patients, 33 were administered adjuvant chemotherapy consisting of oral tegafur-uracil (2 capsules twice daily) for 12 months with (n=4) or without (n=29) preceding intravenous chemotherapy of mitomycin-C, epirubicin, and cisplatin. The remaining 52 patients who did not receive adjuvant chemotherapy served as the control group.
  
  
  RESULTS
  Baseline patient characteristics at diagnosis (age, sex, pathologic type, performance status, T classification, N classification, and overall stage), as well as previous treatment modality, were comparable in both arms. After a median follow-up of 70 months for surviving patients, 45.5% (15 of 33 patients) with adjuvant chemotherapy and 71.2% (37 of 52 patients) without adjuvant chemotherapy experienced tumor relapses (P=.0323). There were a significant reduction in distant failure (P=.0034) but not in local or regional recurrence. The 5-year overall survival rate was 71.6% for patients with adjuvant chemotherapy and 28.7% for patients without adjuvant chemotherapy (hazard ratio 0.27; 95% confidence interval 0.17-0.55; P<.0001).
  
  
  CONCLUSIONS
  Our retrospective data showed that adjuvant chemotherapy can reduce distant failure and improve overall survival in NPC patients with persistently detectable pEBV DNA after curative radiation therapy plus induction/concurrent chemotherapy.
authors.affiliation: Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Otorhinolaryngology, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Chih-Wen
authors.initials: CW
authors.lastname: Twu
authors.affiliation: Section of Basic Medicine, Department of Nursing, Hung Kuang University, Taichung, Taiwan.
authors.forename: Wen-Yi
authors.initials: WY
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Chien-Chih
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Department of Otorhinolaryngology, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Kai-Li
authors.initials: KL
authors.lastname: Liang
authors.affiliation: Department of Otorhinolaryngology, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Rong-San
authors.initials: RS
authors.lastname: Jiang
authors.affiliation: Department of Radiation Oncology, Taichung Veterans General Hospital-Chiayi Branch, Chiayi, Taiwan.
authors.forename: Ching-Te
authors.initials: CT
authors.lastname: Wu
authors.affiliation: Department of Radiation Oncology, St. Martin De Porres Hospital, Chiayi, Taiwan.
authors.forename: Yi-Ting
authors.initials: YT
authors.lastname: Shih
authors.affiliation: Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Po-Ju
authors.initials: PJ
authors.lastname: Lin
authors.affiliation: Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Liu
authors.affiliation: Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Medicine, China Medical University, Taichung, Taiwan. Electronic address: jclin@vghtc.gov.tw.
authors.forename: Jin-Ching
authors.initials: JC
authors.lastname: Lin
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D017024:Chemotherapy, Adjuvant / Q000379:methods / Q000401:mortality; D002945:Cisplatin / Q000008:administration & dosage; D004279:DNA, Viral / Q000097:blood*; D004338:Drug Combinations; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy / Q000821:virology*; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000821:virology; D020266:Radiotherapy, Conformal / Q000379:methods; D012189:Retrospective Studies; D005641:Tegafur / Q000627:therapeutic use; D016896:Treatment Outcome; D014498:Uracil / Q000627:therapeutic use
chemical_list: D015415:Biomarkers; D004279:DNA, Viral; D004338:Drug Combinations; D005641:Tegafur; D015251:Epirubicin; D016685:Mitomycin; D014498:Uracil; D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil