CHLORAMBUCIL INDUCED SEIZURES

BACKGROUND. Anecdotal reports of chlorambucil-induced seizures have sp oradically appeared, mainly in the nononcologic literature. The majori ty of cases have occurred in patients treated with high dose therapy a nd in children with nephrotic syndrome. Because of its rarity, oncolog ists and hematologists may not be aware of this potential complication . METHODS. Two elderly patients with a remote history of seizures had generalized tonic-clonic seizures 3 days after chlorambucil therapy wa s initiated. A MEDLINE search was performed of previously reported cas es and additional cases were found in the bibliographies of retrieved articles. RESULTS. In addition to the 2 new cases presented here, ther e have been 28 reported cases of chlorambucil-induced seizures. Underl ying diseases included nephrotic syndrome (n = 12 cases), solid tumors (n = 10 cases), non-Hodgkin's lymphoma (n = 3 cases), and chronic lym phocytic leukemia (n = 1 case). Five cases were secondary to accidenta l overdose. Sixteen of 30 patients were younger than 18 years; 11 had nephrotic syndrome, 1 had choriocarcinoma, and 4 accidentally ingested the medication. Nine of 14 adults received high dose chlorambucil in Phase I-II studies or as part of a conditioning regimen prior to bone marrow transplantation for solid tumors, 3 were on intermittent pulse therapy, 1 was on daily low dose administration of chlorambucil, and 1 patient had an accidental poisoning. Two patients had recurrent seizu res when they were rechallenged with chlorambucil. CONCLUSIONS. A rela tively high incidence of chlorambucil-induced seizures in children wit h nephrotic syndrome may be due to an increased sensitivity in childho od or altered pharmacokinetics. In adults without a seizure history, s eizures were observed only in patients treated with high dose chloramb ucil; however, in adults with a seizure history, lower doses as used i n pulse therapy also caused seizures. In the latter group of patients, daily low dose chlorambucil or, more likely, an alternative drug may be the safest approach to therapy. (C) 1997 American Cancer Society.