Intra-Arterial Liposomal Adriamycin for Metastatic Adenocarcinoma of the Liver

Abstract

A liposome-entrapped liposome form of Adriamycin (Lip-ADM) has been demonstrated to cause less myocardial and gastrointestinal toxicity than free ADM. In the present study, Lip-ADM prepared by the remote loading method was administered to 3 patients with metastatic adenocarcinoma of the liver via a reservoir with the catheter located in the proper hepatic artery. The primary tumor was gastric cancer in 2 patients and sigmoid colon cancer in 1. Lip-ADM was administered at doses of 10, 20 or 50 mg per time. The total ADM dose was 170, 490, and 760 mg, respectively. No severe adverse effects, such as nausea, vomiting, stomatitis, alopecia or cardiotoxicity, were observed in any of the patients. Although mild leukocytopenia (2,800/µl) was observed in 1 patient, anemia or thrombocytopenia did not occur. The survival time was respectively 6,15, and 17 months from the start of Lip-ADM administration. A partial response was obtained in 1 patient and stable disease in 1 patient. Administration of Lip-ADM via a reservoir appears to be a useful treatment for patients with metastatic adenocarcinoma of the liver, since the low toxicity of this preparation allows an increase of the total dose of ADM.

Antimetastatic Effect of Hepatotropic Liposomal Adriamycin on Human Metastatic Liver Tumors

“…11 Lip-ADM has also been reported to have an excellent clinical therapeutic effect on metastatic liver tumors from gastrointestinal cancer. 28 Pisani et al reported that approximately 400 000 people die of colorectal cancer in the world every year, 29 and liver metastases develop in approximately 60% of patients with colorectal cancer. Liver resection is currently the only treatment that offers long-term survival, following which the 5-year survival rates range from 25% to 40%; however, less than 20% of patients are candidates for resection.…”

NF-KAPPA B liposomes and pathogenesis of hepatic injury and fibrosis

“…It was recently reported that local administration of liposomal Adriamycin through the hepatic artery to three patients with metastatic gastric adenocarcinoma significantly lowered common gastrointestinal and myocardial toxicity when compared to patients treated with the free drug. The patients tolerated the treatment with increased doses of Adriamycin (41). A reduction of renal toxicity and an increase in hepatic uptake of cyclosporine (CsA) have been shown for CsAcontaining liposomes in a liver transplant model in rats (42).…”

Doxorubicin Activity Is Enhanced by Hyperthermia in a Model of Ex Vivo Vascular Perfusion of Human Colon Carcinoma

“…Despite these considerations, interest in the use of DXR for the treatment of advanced colon carcinoma has not faded. For instance, some authors have proposed to exploit the pharmacokinetic advantages provided by a particular drug delivery formulation such as liposomes in the DXR‐based locoregional treatment of liver metastases [8, 9, 10]. We are conducting a pilot study on pelvic perfusion with DXR in patients affected with locally advanced colorectal cancer, and the preliminary results appear encouraging (manuscript in preparation).…”