Cancer Chemotherapy and Pharmacology

, Volume 69, Issue 3, pp 773–780 | Cite as

Phase II trial of sorafenib in combination with 5-fluorouracil infusion in advanced hepatocellular carcinoma

  • Iacopo Petrini
  • Monica Lencioni
  • Miriam Ricasoli
  • Mauro Iannopollo
  • Cinzia Orlandini
  • Filippo Oliveri
  • Carlo Bartolozzi
  • Sergio Ricci
Original Article



Sorafenib improves overall survival and time to progression of advanced hepatocellular (aHCC) patients such as demonstrated in 2 phase III trials. However, aHCC patients’ outcome is still poor despite these results. In order to improve the efficacy of systemic treatment for aHCC, we evaluated the combination of sorafenib plus 5-fluorouacil infusion in a phase II trial.


Patients with aHCC not eligible for loco-regional therapies, Child-Pugh A-B, ECOG-PS 0-1, and without history of anti-cancer systemic treatment were enrolled. Treatment schedule was: sorafenib 400 mg/bid continuously and continuum infusion of 5-fluorouracil 200 mg/sqm/daily day 1–14 every 3 weeks.


Thirty-nine patients were enrolled: ECOG-PS 0-1: 29-10, Child-Pugh A-B: 36-3. Grade 3/4 (%) toxicities included: diarrhea 5.1/0, mucositis 20.5/2.6, hand foot skin reaction 20.5/0, skin rash 10.5/0, hypertension 10.3/0, hyperbilirubinemia 5.1/2.6, glutamic-oxaloacetic transaminase increase 10.3/0, glutamic-pyruvic transaminase increase 7.7/0, cardiac toxicity (one heart failure, two atrial fibrillation cases) 7.7/0, and bleeding (melena) in 2.6/0. One partial response was observed. Stable disease was obtained in 46.2% of patients with a median duration of 16.2 months. Median time to progression was 8 months (CI 95% = 5.7–10.4), and median overall survival was 13.7 months (CI 95% = 9.5–17.9).


The results show an encouraging disease control rate, time to progression, and overall survival. The combination of sorafenib and 5-fluorouracil was feasible, and the side effects were manageable for patients carefully selected for liver function and performance status.


Hepatocellular carcinoma Sorafenib 5-Fluorouracil Chemotherapy Targeted therapy 



Bayer Pharma S.p.A, Milan, Italy founded this research. We thank Dr Clare Paterson and Donna Voeller who helped editing the paper.


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Iacopo Petrini
    • 1
  • Monica Lencioni
    • 2
  • Miriam Ricasoli
    • 2
  • Mauro Iannopollo
    • 2
  • Cinzia Orlandini
    • 2
  • Filippo Oliveri
    • 3
  • Carlo Bartolozzi
    • 4
  • Sergio Ricci
    • 2
  1. 1.Department of Oncology, Transplant and New Advances in Medicine, BIOSUniversity of PisaPisaItaly
  2. 2.Medical OncologyPisa University HospitalPisaItaly
  3. 3.Gastroenterology UnitPisa University HospitalPisaItaly
  4. 4.Department of Diagnostic and Interventional RadiologyPisa UniversityPisaItaly

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