© 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.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  B. K. Yoo, R. Gredler, N. Vozhilla, Z.-z. Su, D. Chen, T. Forcier, K. Shah, U. Saxena, U. Hansen, P. B. Fisher, et al. Identification of genes conferring resistance to 5-fluorouracil PNAS, August 4, 2009; 106(31): 12938 - 12943. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. O. Lee, K. W. Lee, D. Y. Oh, J. H. Kim, S. A. Im, T. Y. Kim, and Y. J. Bang Combination chemotherapy with capecitabine and cisplatin for patients with metastatic hepatocellular carcinoma Ann. Onc., August 1, 2009; 20(8): 1402 - 1407. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Jelic and On behalf of the ESMO Guidelines Working Group Hepatocellular carcinoma: ESMO Clinical Recommendations for diagnosis, treatment and follow-up Ann. Onc., May 1, 2009; 20(suppl_4): iv41 - iv45. [Full Text] [PDF]
|
|
|
|
 |
|
 M. B. Thomas, J. S. Morris, R. Chadha, M. Iwasaki, H. Kaur, E. Lin, A. Kaseb, K. Glover, M. Davila, and J. Abbruzzese Phase II Trial of the Combination of Bevacizumab and Erlotinib in Patients Who Have Advanced Hepatocellular Carcinoma J. Clin. Oncol., February 20, 2009; 27(6): 843 - 850. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. L. Chan, F. K.F. Mo, P. J. Johnson, E. P. Hui, B. B.Y. Ma, W. M. Ho, K. C. Lam, A. T.C. Chan, T. S.K. Mok, and W. Yeo New Utility of an Old Marker: Serial {alpha}-Fetoprotein Measurement in Predicting Radiologic Response and Survival of Patients With Hepatocellular Carcinoma Undergoing Systemic Chemotherapy J. Clin. Oncol., January 20, 2009; 27(3): 446 - 452. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. K. Abou-Alfa Commentary: Sorafenib--The End of a Long Journey in Search of Systemic Therapy for Hepatocellular Carcinoma, or the Beginning? Oncologist, January 1, 2009; 14(1): 92 - 94. [Full Text] [PDF]
|
|
|
|
|
|
R. K. Kelley and A. P. Venook Sorafenib in Hepatocellular Carcinoma: Separating the Hype From the Hope J. Clin. Oncol., December 20, 2008; 26(36): 5845 - 5848. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ikeda, T. Okusaka, H. Ueno, C. Morizane, Y. Kojima, S. Iwasa, and A. Hagihara Predictive Factors of Outcome and Tumor Response to Systemic Chemotherapy in Patients with Metastatic Hepatocellular Carcinoma Jpn. J. Clin. Oncol., October 1, 2008; 38(10): 675 - 682. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Huynh, V. C. Ngo, J. Fargnoli, M. Ayers, K. C. Soo, H. N. Koong, C. H. Thng, H. S. Ong, A. Chung, P. Chow, et al. Brivanib Alaninate, a Dual Inhibitor of Vascular Endothelial Growth Factor Receptor and Fibroblast Growth Factor Receptor Tyrosine Kinases, Induces Growth Inhibition in Mouse Models of Human Hepatocellular Carcinoma Clin. Cancer Res., October 1, 2008; 14(19): 6146 - 6153. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Llovet, S. Ricci, V. Mazzaferro, P. Hilgard, E. Gane, J.-F. Blanc, A. C. de Oliveira, A. Santoro, J.-L. Raoul, A. Forner, et al. Sorafenib in Advanced Hepatocellular Carcinoma N. Engl. J. Med., July 24, 2008; 359(4): 378 - 390. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. V. Tse, M. Hawkins, G. Lockwood, J. J. Kim, B. Cummings, J. Knox, M. Sherman, and L. A. Dawson Phase I Study of Individualized Stereotactic Body Radiotherapy for Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma J. Clin. Oncol., February 1, 2008; 26(4): 657 - 664. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. H. O'Neil and A. P. Venook Hepatocellular Carcinoma: The Role of the North American GI Steering Committee Hepatobiliary Task Force and the Advent of Effective Drug Therapy Oncologist, December 1, 2007; 12(12): 1425 - 1432. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Huynh, P. K.H. Chow, and K.-C. Soo AZD6244 and doxorubicin induce growth suppression and apoptosis in mouse models of hepatocellular carcinoma Mol. Cancer Ther., September 1, 2007; 6(9): 2468 - 2476. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Alberts, G. J. Gores, G. P. Kim, L. R. Roberts, M. L. Kendrick, C. B. Rosen, S. T. Chari, and J. A. Martenson Treatment Options for Hepatobiliary and Pancreatic Cancer Mayo Clin. Proc., May 1, 2007; 82(5): 628 - 637. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Yuan, J. Wang, J. Li, L. Wang, M. Li, Z. Yang, C. Zhang, and J. L. Dai Frequent Epigenetic Inactivation of Spleen Tyrosine Kinase Gene in Human Hepatocellular Carcinoma. Clin. Cancer Res., November 15, 2006; 12(22): 6687 - 6695. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. K. Abou-Alfa, L. Schwartz, S. Ricci, D. Amadori, A. Santoro, A. Figer, J. De Greve, J.-Y. Douillard, C. Lathia, B. Schwartz, et al. Phase II Study of Sorafenib in Patients With Advanced Hepatocellular Carcinoma J. Clin. Oncol., September 10, 2006; 24(26): 4293 - 4300. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. X. Zhu Systemic Therapy of Advanced Hepatocellular Carcinoma: How Hopeful Should We Be? Oncologist, July 1, 2006; 11(7): 790 - 800. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. X. Zhu, L. S. Blaszkowsky, D. P. Ryan, J. W. Clark, A. Muzikansky, K. Horgan, S. Sheehan, K. E. Hale, P. C. Enzinger, P. Bhargava, et al. Phase II Study of Gemcitabine and Oxaliplatin in Combination With Bevacizumab in Patients With Advanced Hepatocellular Carcinoma J. Clin. Oncol., April 20, 2006; 24(12): 1898 - 1903. [Abstract] [Full Text] [PDF]
|
|