Treatment of unresectable cholangiocarcinoma: conventional transarterial chemoembolization compared with drug eluting bead-transarterial chemoembolization and systemic chemotherapy

Eur J Gastroenterol Hepatol. 2012 Apr;24(4):437-43. doi: 10.1097/MEG.0b013e3283502241.

Abstract

Background: Unresectable cholangiocarcinoma (CCC) has a poor prognosis. Patients with intrahepatic CCC have a very limited benefit from systemic chemotherapy (ChT). The aim of this prospective study was to evaluate the feasibility, safety, and efficacy of conventional transarterial chemoembolization (cTACE) with mitomycin-C and of irinotecan-eluting beads (iDEB-TACE), and to retrospectively compare them with ChT with oxaliplatin and gemcitabine.

Materials and methods: Between June 2002 and June 2010, three independent prospective trials were carried out and compared retrospectively. Following predefined study protocols, 26 patients with histologically proven intrahepatic CCC were treated with iDEB-TACE (200 mg irinotecan), 10 patients were treated with cTACE using 15 mg mitomycin-C mixed with 5-10 ml of ionized oil (lipiodol), followed by embolization with gelfoam, and 31 patients received systemic ChT with gemcitabine and oxaliplatin. Treatment response and progression-free survival (PFS) were assessed by computer tomography or MRI every 2 months according to Response Evaluation Criteria in Solid Tumors. Clinical and laboratory data were assessed for side-effects according to National Cancer Institute-Common Toxicity Criteria.

Results: iDEB-TACE resulted in PFS of 3.9 months and overall survival (OS) of 11.7 months, compared with a PFS of 1.8 months and OS of 5.7 months, respectively, in patients treated with cTACE, and a PFS of 6.2 months and OS of 11.0 months, respectively, in patients treated with oxaliplatin and gemcitabine. The medium follow-up of patients treated with iDEB-TACE was 12 months; 2 months after treatment, 13 patients (50%) had progressive disease, 11 patients (42%) had stable disease, and one patient had a partial response and became eligible for secondary liver resection. Local tumor control was achieved in 66% of patients; 4% had a partial response, 62% had stable disease, and 27% progressive disease. Common Toxicity Criteria grade III or IV toxicities for iDEB-TACE were abdominal pain (n=7), hepatic abscess (n=1), pleural empyema due to biliary leakage (n=1), and one death due to cholangitis with hepatic failure in a patient with liver cirrhosis. No hematological side-effects were observed. Almost every patient experienced a 'postembolization syndrome' with low-grade fever, nausea, and abdominal pain for up to 2 weeks.

Conclusion: This is the first study demonstrating that treatment of patients suffering from intrahepatic CCC with iDEB-TACE is safe in patients with normal liver function, and results in a prolongation of PFS and OS. Local tumor control, PFS and OS seem similar to systemic ChT with oxaliplatin and gemcitabine, but superior to cTACE.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / adverse effects
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Agents, Phytogenic / adverse effects
  • Bile Duct Neoplasms / therapy*
  • Bile Ducts, Intrahepatic*
  • Camptothecin / administration & dosage
  • Camptothecin / adverse effects
  • Camptothecin / analogs & derivatives
  • Chemoembolization, Therapeutic / adverse effects
  • Chemoembolization, Therapeutic / methods*
  • Cholangiocarcinoma / therapy*
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives
  • Epidemiologic Methods
  • Female
  • Gelatin Sponge, Absorbable / administration & dosage
  • Gelatin Sponge, Absorbable / adverse effects
  • Gemcitabine
  • Humans
  • Irinotecan
  • Kaplan-Meier Estimate
  • Liver Neoplasms / therapy*
  • Male
  • Microspheres
  • Middle Aged
  • Mitomycin / administration & dosage
  • Mitomycin / adverse effects
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / adverse effects
  • Oxaliplatin
  • Treatment Outcome

Substances

  • Antibiotics, Antineoplastic
  • Antineoplastic Agents, Phytogenic
  • Organoplatinum Compounds
  • Oxaliplatin
  • Deoxycytidine
  • Mitomycin
  • Irinotecan
  • Camptothecin
  • Gemcitabine