Phase I/II study of the lipiodolization using DDP-H (CDDP powder; IA-call(®)) in patients with unresectable hepatocellular carcinoma

Cancer Chemother Pharmacol. 2010 Jan;65(2):301-7. doi: 10.1007/s00280-009-1034-5.

Abstract

Purpose: Lipiodol Ultra-Fluid (Lipiodol(®)), an oily contrast medium, is selectively retained in hepatocellular carcinoma (HCC) through hepatic arterial infusion. DDP-H (IA-call(®)) developed as a CDDP powder, and may be a possible chemotherapeutic agent with lipiodol. We carried out a phase I/II study of the lipiodolization using DPP-H in patients with unresectable HCC.

Methods: Phase I and pharmacokinetic study: The dose-limiting toxicity (DLT), the maximum tolerance dose (MTD), and the recommended dose (RD) were determined using a modified Fibonacci scheme. The concentration-time profile of total platinum in plasma was analyzed. Phase II study: Thirty-five patients with unresectable HCC received lipiodolization using DDP-H under RD, and the efficacy and safety were assessed.

Results: DLT was grade 3 vomiting at 40 mg/m(2). Therefore, MTD and RD were 35 mg/m(2). The peak of total platinum in plasma was over 1.0 μg/ml at 40 mg/m(2) at 30 min after infusion. Of the 35 patients, 16 (45.7%) demonstrated complete responses, and 4 (11.4%) demonstrated partial responses with an additional 9 patients (25.7%) having stable diseases, as assessed by RECIST. Grade 3 thrombocytopenia was found in 1 patient (2.9%), grade 2 hyperbilirubinemia was found in 2 patients (5.7%), and grade 2 vomiting was found in 4 patients (11.4%).

Conclusion: Lipiodolization using DDP-H at 35 mg/m(2) is effective and well tolerated in patients with unresectable HCC.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II

MeSH terms

  • Aged
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Hepatocellular / drug therapy*
  • Cisplatin / administration & dosage
  • Cisplatin / pharmacokinetics
  • Cisplatin / therapeutic use*
  • Contrast Media
  • Ethiodized Oil*
  • Female
  • Hepatic Artery
  • Humans
  • Infusions, Intra-Arterial
  • Liver Neoplasms / drug therapy*
  • Male
  • Maximum Tolerated Dose
  • Suspensions
  • Tomography, X-Ray Computed

Substances

  • Antineoplastic Agents
  • Contrast Media
  • Suspensions
  • Ethiodized Oil
  • Cisplatin