Procarbazine is an orally administered alkylating agent used in combination with other anti-neoplastic agents in the therapy of Hodgkin’s disease and malignant melanoma. Procarbazine therapy has been associated with serum enzyme elevations during therapy and with rare cases of idiosyncratic, clinically apparent acute liver injury.
Procarbazine (proe kar' ba zeen) is a methylhydrazine derivative which is activated in the liver to highly reactive alkylating intermediates. These intermediates methylate DNA which causes inhibition of DNA, RNA and protein synthesis and cell death. Procarbazine was approved for use in the United States in 1969 and it remains a commonly used agent in the treatment of Hodgkin’s and non-Hodgkin’s lymphomas and brain cancer. Procarbazine is rarely used alone, but is found in common cancer chemotherapeutic regimens such as MOPP (mechlorethamine, vincristine [oncovin], procarbazine and prednisone), COPP (cyclophosphamide, vincristine [oncovin], procarbazine and prednisone), and PCV (procarbazine, lomustine [CCNU], vincristine). Procarbazine is available as tablets of 50 mg generically and under the brand name Matulane. It is typically given in monthly or every other month cycles of 10 to 14 days in a dose of 100 mg per meter squared body surface area. Common side effects are alopecia, anoxia, nausea, vomiting, headache, peripheral neuropathy, and flu-like illness.
Mild and transient elevations in serum aminotransferase levels are not uncommon during courses of systemic combination chemotherapy and the role of procarbazine in these abnormalities is often not clear. However, dose modification for serum enzyme elevations is rarely necessary. Clinically apparent liver disease with fever and marked elevations in serum aminotransferase levels without jaundice has been reported but is very rare.
Mechanism of Injury
The mechanism of hepatotoxicity from procarbazine is not known, but may be due to hypersensitivity.
Outcome and Management
The severity of liver injury from procarbazine is usually mild and self limiting. Procarbazine therapy has not been associated with cases of acute liver failure, chronic liver injury or vanishing bile duct syndrome. A single case report described self-limited, hepatocellular injury without jaundice during a second course of combination therapy and recurrence upon rechallenge with procarbazine, but not with the other antineoplastic agents being used.
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