A phase I study of hepatic arterial infusion chemotherapy with zinostatin stimalamer alone for hepatocellular carcinoma.

Abstract

BACKGROUND:

Hepatic arterial infusion of zinostatin stimalamer and lipiodol emulsion shows a moderate activity against hepatocellular carcinoma. However, the anti-tumor activity of zinostatin stimalamer alone is uncertain.

METHODS:

The primary endpoint was to evaluate the frequency of dose-limiting toxicity and determine the maximum-tolerated dose of zinostatin stimalamer when used by intra-arterial infusion. The candidates for this study were patients with hepatocellular carcinoma no longer amenable to established forms of treatment. Hepatic arterial infusion chemotherapy was performed by selectively introducing a catheter into the hepatic artery with zinostatin stimalamer alone. Treatment was repeated at 4-8-week intervals until disease progression or the appearance of unacceptable toxicity. The starting dose of zinostatin stimalamer was 3 mg/m(2), and doses were increased in 1 mg/m(2) increments in successive cohorts. At least three patients were treated at each dose level and three additional patients were treated in the presence of dose-limiting toxicity.

RESULTS:

Twelve patients were entered into this trial. Dose-limiting toxicity was observed in one of six patients at 3 mg/m(2), and in two of six patients at 4 mg/m(2). The maximum-tolerated dose was judged to be 3 mg/m(2) with liver dysfunction and serum creatinine increase as the dose-limiting toxicity. There was one early death suggested to be related to the protocol treatment. None of the 12 patients achieved an objective tumor response.

CONCLUSION:

Hepatic arterial infusion with a zinostatin stimalamer of 3 mg/m(2) may be tolerated, but not active, in patients with far advanced hepatocellular carcinoma.

• Authors: Hiroshi Ishii, Junji Furuse, Michitaka Nagase, Yasushi Maru, Masahiro Yoshino, Takayuki Hayashi
• Journal: Japanese journal of clinical oncology (Jpn J Clin Oncol) Vol. 33 Issue 11 Pg. 570-3 (Nov 2003) ISSN: 0368-2811 [Print] England
• PMID: 14711981 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article)

Chemical References

• Antineoplastic Agents
• Maleic Anhydrides
• Polystyrenes
• poly(maleic acid-styrene)neocarzinostatin
• Iodized Oil
• Zinostatin

Topics

• Aged
• Antineoplastic Agents (administration & dosage)
• Carcinoma, Hepatocellular (drug therapy)
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Female
• Hepatic Artery
• Humans
• Infusions, Intra-Arterial
• Iodized Oil (administration & dosage)
• Liver Neoplasms (drug therapy)
• Male
• Maleic Anhydrides (administration & dosage)
• Middle Aged
• Polystyrenes (administration & dosage)
• Zinostatin (administration & dosage, analogs & derivatives)