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


CONCLUSIONS
Lipiodolization using DDP-H at 35 mg/m(2) is effective and well tolerated in patients with unresectable HCC.
Yamashita
Yo-ichi
Y
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Maidashi, Higashi-ku, Fukuoka, Japan. yamashi@surg2.med.kyushu-u.ac.jp
Taketomi
Akinobu
A
Itoh
Shinji
S
Harimoto
Norifumi
N
Morita
Kazutoyo
K
Fukuhara
Takasuke
T
Ueda
Shigeru
S
Sanefuji
Kensaku
K
Sugimachi
Keishi
K
Tajima
Tsuyoshi
T
Maehara
Yoshihiko
Y
D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003287:Contrast Media; D004998:Ethiodized Oil; D005260:Female; D006499:Hepatic Artery; D006801:Humans; D007261:Infusions, Intra-Arterial; D008113:Liver Neoplasms / Q000188:drug therapy*; D008297:Male; D020714:Maximum Tolerated Dose; D013535:Suspensions; D014057:Tomography, X-Ray Computed
D000970:Antineoplastic Agents; D003287:Contrast Media; D013535:Suspensions; D004998:Ethiodized Oil; D002945:Cisplatin