© 2005 Oxford University Press
ARTICLE |
A Randomized Phase III Study of Doxorubicin Versus Cisplatin/Interferon 
-2b/Doxorubicin/Fluorouracil (PIAF) Combination Chemotherapy for Unresectable Hepatocellular Carcinoma
Affiliations of authors: Departments of Clinical Oncology (WY, TSM, TWTL, JK, FKFM, ATC, PH, BM, KCL, WMH, HTW, AT), Surgery (PBSL, WYL), and Diagnostic Radiology and Organ Imaging (SCHY), Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China; Comprehensive Cancer Trials Unit, Sir Y. K. Pao Cancer Centre, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China (BZ); Cancer Research UK, Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham, United Kingdom (PJJ)
Correspondence to: Benny Zee, PhD, Comprehensive Cancer Trials Unit, Sir Y. K. Pao Cancer Centre, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China (e-mail: benny{at}clo.cuhk.edu.hk).
Background: Single-agent doxorubicin has been widely used to treat unresectable hepatocellular carcinoma (HCC), but the response rate is low (<20%) and there is no convincing evidence for improved survival. Cisplatin, interferon, doxorubicin, and fluorouracil (PIAF) used in combination, by contrast, has shown promise in a phase II study. We compared doxorubicin to PIAF in patients with unresectable HCC in a phase III trial. Methods: Patients with histologically confirmed unresectable HCC were randomly assigned to receive either doxorubicin or PIAF every 3 weeks, for up to six cycles. The primary endpoint was overall survival, and secondary endpoints were response rate and toxicity. Survival differences were calculated using the Kaplan-Meier method. Treatment groups were compared for differences in the incidence of adverse events using chi-square tests. All statistical tests were two-sided. Results: The median survival of the doxorubicin and PIAF groups was 6.83 months (95% confidence [CI] = 4.80 to 9.56) and 8.67 months (95% CI = 6.36 to 12.00), respectively (P = 0.83). The hazard ratio for death from any cause in the PIAF compared with the doxorubicin groups was 0.97 (95% CI = 0.71 to 1.32). Eighty-six of the 94 patients receiving doxorubicin and 91 of the 94 receiving PIAF were assessable for response. The overall response rates in the doxorubicin and PIAF groups were 10.5% (95% CI = 3.9% to 16.9%) and 20.9% (95% CI = 12.5% to 29.2%), respectively. Neutropenia, thrombocytopenia, and hypokalemia were statistically significantly more common in patients treated with PIAF than in patients treated with doxorubicin. Conclusion: Although patients on PIAF had a higher overall response rate and better survival than patients on doxorubicin, the differences were not statistically significant. PIAF was also associated with increased treatment-related toxicity. The prognosis of patients with unresectable HCC remains poor.
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