Shukui Qin1, Yuxian Bai, Ho Yeong Lim, Sumitra Thongprasert, Yee Chao, Jia Fan, Tsai-Shen Yang, Vajarabhongsa Bhudhisawasdi, Won Ki Kang, Yu Zhou, Jee Hyun Lee, Yan Sun. 1. 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.
Abstract
PURPOSE: 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. PATIENTS AND 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. CONCLUSION: 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.
RCT Entities:
PURPOSE: 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. PATIENTS AND 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. CONCLUSION: 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.