title: Randomized, multicenter, open-label study of oxaliplatin plus fluorouracil/leucovorin versus doxorubicin as palliative chemotherapy in patients with advanced hepatocellular carcinoma from Asia.
abstract: OBJECTIVE
  To determine whether FOLFOX4 (infusional fluorouracil, leucovorin, and oxaliplatin) administered as palliative chemotherapy to patients with advanced hepatocellular carcinoma (HCC) provides a survival benefit and efficacy versus doxorubicin.
  
  
  METHODS
  This multicenter, open-label, randomized, phase III study in mainland China, Taiwan, Korea, and Thailand involved 371 patients age 18 to 75 years who had locally advanced or metastatic HCC and were ineligible for curative resection or local treatment. They were randomly assigned at a ratio of one to one to receive either FOLFOX4 (n = 184) or doxorubicin (n = 187). The primary end point was overall survival (OS); secondary end points included progression-free survival (PFS), response rate (RR) by RECIST (version 1.0), and safety.
  
  
  RESULTS
  At the prespecified final analysis, median OS was 6.40 months with FOLFOX4 (95% CI, 5.30 to 7.03) and 4.97 months with doxorubicin (95% CI, 4.23 to 6.03; P = .07; hazard ratio [HR], 0.80; 95% CI, 0.63 to 1.02). Median PFS was 2.93 months with FOLFOX4 (95% CI, 2.43 to 3.53), and 1.77 months with doxorubicin (95% CI, 1.63 to 2.30; P < .001; HR, 0.62; 95% CI, 0.49 to 0.79). RR was 8.15% with FOLFOX4 and 2.67% with doxorubicin (P = .02). On continued follow-up, the trend toward increased OS with FOLFOX4 was maintained (P = .04; HR, 0.79; 95% CI, 0.63 to 0.99). Toxicity was consistent with previous experiences with FOLFOX4; proportions of grade 3 to 4 adverse events were similar between treatments.
  
  
  CONCLUSIONS
  Although the study did not meet its primary end point, the trend toward improved OS with FOLFOX4, along with increased PFS and RR, suggests that this regimen may confer some benefit to Asian patients, but an OS benefit cannot be concluded from these data.
authors: Shukui Qin, People's Liberation Army Cancer Centre, Bayi Hospital, Nanjing; Yuxian Bai, Third Affiliated Hospital, Harbin Medical University, Harbin; Jia Fan, Zhongshan Hospital, Fudan University; Yu Zhou, sanofi-aventis Asia, Shanghai; Yan Sun, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, China; Ho Yeong Lim and Won Ki Kang, Samsung Medical Centre; Won Ki Kang, Sungkyunkwan University School of Medicine; Jee Hyun Lee, sanofi-aventis Korea, Seoul, Korea; Sumitra Thongprasert, Chiang Mai University, Chiang Mai; Vajarabhongsa Bhudhisawasdi, Khon Kaen University, Khon Kaen, Thailand; Yee Chao, Taipei Veterans General Hospital, Taipei; and Tsai-Shen Yang, Chang Gung Memorial Hospital, LinKou Medical Center, Chang Gung University, Taoyuan, Taiwan.
authors: Shukui
authors: S
authors: Qin
authors: Yuxian
authors: Y
authors: Bai
authors: Ho Yeong
authors: HY
authors: Lim
authors: Sumitra
authors: S
authors: Thongprasert
authors: Yee
authors: Y
authors: Chao
authors: Jia
authors: J
authors: Fan
authors: Tsai-Shen
authors: TS
authors: Yang
authors: Vajarabhongsa
authors: V
authors: Bhudhisawasdi
authors: Won Ki
authors: WK
authors: Kang
authors: Yu
authors: Y
authors: Zhou
authors: Jee Hyun
authors: JH
authors: Lee
authors: Yan
authors: Y
authors: Sun
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D007390:International Agencies; D002955:Leucovorin / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010166:Palliative Care; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate; D055815:Young Adult
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D004317:Doxorubicin; D002955:Leucovorin; D005472:Fluorouracil