Modified cisplatin/interferon α-2b/doxorubicin/5-fluorouracil (PIAF) chemotherapy in patients with no hepatitis or cirrhosis is associated with improved response rate, resectability, and survival of initially unresectable hepatocellular carcinoma

Cancer. 2013 Sep 15;119(18):3334-42. doi: 10.1002/cncr.28209. Epub 2013 Jul 2.

Abstract

Background: The purpose of this study was to evaluate the factors associated with response rate, resectability, and survival after cisplatin/interferon α-2b/doxorubicin/5-fluorouracil (PIAF) combination therapy in patients with initially unresectable hepatocellular carcinoma.

Methods: The study included 2 groups of patients treated with conventional high-dose PIAF (n = 84) between 1994 and 2003 and those without hepatitis or cirrhosis treated with modified PIAF (n = 33) between 2003 and 2012. Tolerance of chemotherapy, best radiographic response, rate of conversion to curative surgery, and overall survival were analyzed and compared between the 2 groups, and multivariate and logistic regression analyses were applied to identify predictors of response and survival.

Results: The modified PIAF group had a higher median number of PIAF cycles (4 versus 2, P = .049), higher objective response rate (36% versus 15%, P = .013), higher rate of conversion to curative surgery (33% versus 10%, P = .004), and longer median overall survival (21.3 versus 10.6 months, P = .002). Multivariate analyses confirmed that positive hepatitis B serology (hazard ratio [HR] = 1.68; 95% confidence interval [CI] = 1.08-2.59) and Eastern Cooperative Oncology Group performance status ≥ 2 (HR = 1.75; 95% CI = 1.04-2.93) were associated with worse survival whereas curative surgical resection after PIAF treatment (HR = 0.15; 95% CI = 0.07-0.35) was associated with improved survival.

Conclusions: In patients with initially unresectable hepatocellular carcinoma, the modified PIAF regimen in patients with no hepatitis or cirrhosis is associated with improved response, resectability, and survival.

Keywords: PIAF; chemotherapy; downsizing; hepatocellular carcinoma; liver resection; response; survival; tolerance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / surgery
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Cisplatin / therapeutic use
  • Clinical Trials, Phase II as Topic
  • Cohort Studies
  • Doxorubicin / administration & dosage
  • Doxorubicin / adverse effects
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / administration & dosage
  • Interferon-alpha / adverse effects
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / surgery
  • Middle Aged
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / adverse effects
  • Retrospective Studies
  • Survival Analysis
  • Young Adult

Substances

  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Doxorubicin
  • Cisplatin
  • Fluorouracil