Reappraisal of the use of procarbazine in the treatment of lymphomas and brain tumors

Abstract

Procarbazine HCl is a 'nonclassical' oral alkylating anticancer agent that was first synthesized in the late 1950s. It has been used in the treatment of many cancers, but its main use is in the treatment of Hodgkin's lymphoma and brain tumors and, to a lesser extent, Non-Hodgkin's lymphoma and primary central nervous system lymphoma. Procarbazine is a prodrug that undergoes metabolic transformation into active intermediates that are thought to inhibit DNA, RNA, and protein synthesis. Early use of procarbazine in combination with mechlorethamine, vincristine, and prednisone (MOPP) was effective in the treatment of advanced Hodgkin's lymphoma, but late toxic effects such as secondary cancer and infertility led to its replacement by other regimens. However, its recent reintroduction in the dose-intensified BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) regimen has yielded very promising findings. Procarbazine alone, or more commonly combined in the PCV (procarbazine, lomustine [CCNU], and vincristine) regimen, is also effective in treating gliomas comprising astrocytomas, glioblastomas, and oligodendrogliomas. The most common side effects of procarbazine are gastrointestinal disturbances, myelosuppression, and central nervous system effects. In conclusion, the use of procarbazine in combination with other drugs means that it remains a major anticancer drug in the management of Hodgkin's lymphoma and gliomas.