Intravenous thiotepa for treatment of breast cancer-related leptomeningeal carcinomatosis: case series

Leptomeningeal carcinomatosis (LMC) secondary to metastatic breast cancer (MBC) has increased in incidence with improved systemic disease control. Current treatment options include radiation therapy (to symptomatic sites) and systemic treatment [intrathecal (IT) or intravenous (IV) chemotherapy]. Methotrexate (MTX), thiotepa and cytarabine are the most commonly used IT agents, while high-dose MTX is the most common IV regimen. While IT treatments are generally well tolerated, complications like chemical meningitis, leukoencephalopathy, etc. occur. LMC may cause a breakdown in the blood-brain barrier and thus allow systemic agents to penetrate; however, efficacy is reported only for agents administered at high doses (MTX). We report our institution's experience in using IV thiotepa as treatment for LMC secondary to MBC. We conducted a retrospective chart review of 13 patients with MBC who developed LMC and treated with IV thiotepa at our institution. It was administered at 40 mg/m(2) every 21 days; median number of thiotepa cycles administered was 5 with the major dose-limiting toxicity being myelosuppression. Four had partial response, 3 had stable disease and 6 had progressive disease. The 6-month survival rate was 69 % and 1-year survival rate was 31 %. Despite retrospective nature of our case series, we found the use of IV thiotepa as sole treatment for LMC in patients with MBC to be well tolerated, easily administered in the ambulatory setting, and with efficacy comparable to the other chemotherapeutic agents commonly used in the treatment of LMC. This regimen warrants further investigation in prospective studies.