Pilot Study of Albendazole in Patients with Advanced Malignancy

Abstract

Our preclinical studies have shown that the widely used antiparasitic drug albendazole has potent antiproliferative activity against colorectal cancer (CRC) and hepatocellular carcinoma (HCC). This trial was designed to evaluate albendazole in a small number of patients (n = 7) with either HCC or CRC and hepatic metastases refractory to other forms of therapy. Albendazole was given at 10 mg/kg/day orally in two divided doses for a period of 28 days. To follow the effect of treatment, tumor markers, carcinoembryonic antigen (CEA) or α-feto protein (AFP), were measured routinely in these patients. A range of hematological and biochemical indices were also serially measured to monitor bone marrow, kidney or liver toxicity. Albendazole therapy resulted in a decrease in CEA in 2 patients. In the remaining 5 with measurable tumor markers, serum CEA or AFP was stabilized in 3 patients, while in the other 2, after an initial stabilization (5–10 days), the markers began to increase. In the 7 patients completing the trial, albendazole was well tolerated and there were no significant changes in any hematological, kidney or liver function tests, but 3 patients were withdrawn for severe neutropenia which was probably contributory to the death of 1 patient. These data support our previous experimental results demonstrating that albendazole has antitumor effects.

Death Related to Albendazole-Induced Pancytopenia: Case Report and Review

“…Neutropenia reached 33% in a phase 1 chemotherapy trial in which all patients had significant replacement of the liver with cancer. 7,9 In another study of echinococcus treatment, 2 of 12 patients developed neutropenia. One of the two patients had complete biliary obstruction from echinococcal disease.…”

Presumptive Albendazole Toxicosis in 12 Alpacas

“…3 In humans, idiosyncratic albendazole toxicosis occurs, especially in patients with liver disease, with long-term albendazole therapy used as either an antiparasitic drug to treat hydatid disease or as an antiproliferative drug in the treatment of certain neoplasias. 7,11,12 The dogs and cat in which toxicosis occurred were also treated for several consecutive days for giardiasis. 6,10 The idiosyncratic signs seen in humans, dogs, and cats are similar to those seen in these camelids, and include severe neutropenia, thrombocytopenia, pancytopenia, and GI signs (dogs only).…”

“…6,10 The idiosyncratic signs seen in humans, dogs, and cats are similar to those seen in these camelids, and include severe neutropenia, thrombocytopenia, pancytopenia, and GI signs (dogs only). 6,7,10,11,12 It is unclear why humans and cats do not show evidence of GI lesions of albendazole toxicity, as the proposed mechanism of the toxic effects is theorized to be the antiproliferative activity of the drug. 6,7 The similarity of the bone-marrow lesions in other species receiving long-term albendazole therapy to those seen in the camelids of this report suggests that multiple dosing played an important role in the clinical signs.…”

“…[5][6][7][8][9][10] Albendazole administration to humans causes clinical abnormalities including pancytopenia, neutropenia, and thrombocytopenia, occasionally resulting in death from sepsis secondary to severe neutropenia. 7,11,12 It has also been associated with severe, reversible leukopenia, and thrombocytopenia in dogs and a cat, 6,10 whereas high-dose fenbendazole (2,000 mg/kg PO for 14 days) causes leukopenia and thrombocytopenia in swine. 5 This report describes the clinical and laboratory findings of presumed albendazole toxicosis in 2 alpaca herds.…”

Synthesis of 5‐Substituted 2‐Methylbenzimidazoles with Anticancer Activity

“…The widely used antiparasitic drug albendazole has potent antiproliferative activity against colorectal cancer (CRC) and hepatocellular carcinoma (HCC) [5,6]. …”