title: Concurrent chemo-radiation with or without induction gemcitabine, Carboplatin, and Paclitaxel: a randomized, phase 2/3 trial in locally advanced nasopharyngeal carcinoma.
abstract: OBJECTIVE
  To compare survival, tumor control, toxicities, and quality of life of patients with locally advanced nasopharyngeal carcinoma (NPC) treated with induction chemotherapy and concurrent chemo-radiation (CCRT), against CCRT alone.
  
  
  METHODS
  Patients were stratified by N stage and randomized to induction GCP (3 cycles of gemcitabine 1000 mg/m(2), carboplatin area under the concentration-time-curve 2.5, and paclitaxel 70 mg/m(2) given days 1 and 8 every 21 days) followed by CCRT (radiation therapy 69.96 Gy with weekly cisplatin 40 mg/m(2)), or CCRT alone. The accrual of 172 was planned to detect a 15% difference in 5-year overall survival (OS) with a 5% significance level and 80% power.
  
  
  RESULTS
  Between September 2004 and August 2012, 180 patients were accrued, and 172 (GCP 86, control 86) were analyzed by intention to treat. There was no significant difference in OS (3-year OS 94.3% [GCP] vs 92.3% [control]; hazard ratio 1.05; 1-sided P=.494]), disease-free survival (hazard ratio 0.77, 95% confidence interval 0.44-1.35, P=.362), and distant metastases-free survival (hazard ratio 0.80, 95% confidence interval 0.38-1.67, P=.547) between the 2 arms. Treatment compliance in the induction phase was good, but the relative dose intensity for concurrent cisplatin was significantly lower in the GCP arm. Overall, the GCP arm had higher rates of grades 3 and 4 leukopenia (52% vs 37%) and neutropenia (24% vs 12%), but grade 3 and 4 acute radiation toxicities were not statistically different between the 2 arms. The global quality of life scores were comparable in both arms.
  
  
  CONCLUSIONS
  Induction chemotherapy with GCP before concurrent chemo-irradiation did not improve survival in locally advanced NPC.
authors.affiliation: Division of Radiation Oncology, National Cancer Centre Singapore, Singapore. Electronic address: trdtwk@nccs.com.sg.
authors.forename: Terence
authors.initials: T
authors.lastname: Tan
authors.affiliation: Division of Medical Oncology, National Cancer Centre Singapore, Singapore.
authors.forename: Wan-Teck
authors.initials: WT
authors.lastname: Lim
authors.affiliation: Division of Radiation Oncology, National Cancer Centre Singapore, Singapore.
authors.forename: Kam-Weng
authors.initials: KW
authors.lastname: Fong
authors.affiliation: Division of Radiation Oncology, National Cancer Centre Singapore, Singapore.
authors.forename: Shie-Lee
authors.initials: SL
authors.lastname: Cheah
authors.affiliation: Division of Radiation Oncology, National Cancer Centre Singapore, Singapore.
authors.forename: Yoke-Lim
authors.initials: YL
authors.lastname: Soong
authors.affiliation: Division of Medical Oncology, National Cancer Centre Singapore, Singapore.
authors.forename: Mei-Kim
authors.initials: MK
authors.lastname: Ang
authors.affiliation: Division of Medical Oncology, National Cancer Centre Singapore, Singapore.
authors.forename: Quan-Sing
authors.initials: QS
authors.lastname: Ng
authors.affiliation: Division of Medical Oncology, National Cancer Centre Singapore, Singapore.
authors.forename: Daniel
authors.initials: D
authors.lastname: Tan
authors.affiliation: Division of Clinical Trial and Epidemiological Sciences, National Cancer Centre Singapore, Singapore.
authors.forename: Whee-Sze
authors.initials: WS
authors.lastname: Ong
authors.affiliation: Division of Clinical Trial and Epidemiological Sciences, National Cancer Centre Singapore, Singapore.
authors.forename: Sze-Huey
authors.initials: SH
authors.lastname: Tan
authors.affiliation: Division of Radiation Oncology, National Cancer Centre Singapore, Singapore.
authors.forename: Connie
authors.initials: C
authors.lastname: Yip
authors.affiliation: Division of Radiation Oncology, National Cancer Centre Singapore, Singapore.
authors.forename: Daniel
authors.initials: D
authors.lastname: Quah
authors.affiliation: Division of Surgical Oncology, National Cancer Centre Singapore, Singapore.
authors.forename: Khee-Chee
authors.initials: KC
authors.lastname: Soo
authors.affiliation: Division of Radiation Oncology, National Cancer Centre Singapore, Singapore.
authors.forename: Joseph
authors.initials: J
authors.lastname: Wee
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002277:Carcinoma; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods*; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D017239:Paclitaxel / Q000008:administration & dosage; D010349:Patient Compliance; D011788:Quality of Life; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage; D000093542:Gemcitabine
chemical_list: D011838:Radiation-Sensitizing Agents; D003841:Deoxycytidine; D016190:Carboplatin; D017239:Paclitaxel; D002945:Cisplatin; D000093542:Gemcitabine