17P - Intravenous thiotepa for treatment of leptomeningeal carcinomatosis: Retrospective case series

Date 07 May 2015
Event IMPAKT 2015
Session Welcome reception and Poster Walk
Topics Anti-Cancer Agents & Biologic Therapy
Breast Cancer, Metastatic
Presenter Jaspreet Chahal
Citation Annals of Oncology (2015) 26 (suppl_3): 6-9. 10.1093/annonc/mdv115
Authors J. Chahal1, P. Chalasani2, A. Stopeck3, K. Clarke2, R.B. Livingston2
  • 1Internal Medicine, University of Arizona, 85724 - Tucson/US
  • 2Hematology And Oncology, University of Arizona Cancer Center, 85724 - Tucson/US
  • 3Hematology And Oncology, University of Arizona Cancer Center, 85719 - Tucson/US

Abstract

Body

Introduction: Leptomeningeal carcinomatosis (LMC) is a devastating complication of metastatic breast cancer (MBC) with median survival of 3-6 months. Current treatment is intrathecal (IT) or intravenous (IV) chemotherapy, but lacks standardization. Methotrexate (MTX), thiotepa (TT), and cytarabine are commonly used IT agents while high dose MTX is the most reported IV agent. IT therapy carries complications of chemical meningitis and encephalopathy, and requires administration by ommaya reservoir. Treatment efficacy is reported with high dose IV MTX since LMC causes breakdown of blood-brain barrier (BBB) and allows systemic agents to penetrate cerebrospinal fluid (CSF). MTX, however, causes severe myelosuppression, hepatic toxicity, and frequently requires hospitalization for monitoring. TT also penetrates BBB when given IV due to its lipophilic nature, but is not frequently used. We report our institution's experience in using IV TT as treatment for LMC in MBC patients.

Methods and results: We conducted a retrospective chart review of 13 MBC patients who developed LMC and were treated with IV TT at our institution between 2010 and 2013. IV TT was administered at 40mg/m2 every 21 days. LCM was diagnosed by malignant cells in CSF in 5/13 patients or magnetic resonance imaging (MRI) (12/13). Median number of cycles given were 5 (range 2-16). Responses based on clinical evaluation and MRI or CSF: 4 partial, 3 stable, and 6 progressive. Median time to progression was 4 months (range 1-17). IV TT was well-tolerated and majority developed no toxicities. Most common toxicity was low-grade thrombocytopenia.

Discussion: LCM is a life threatening complication with limited treatment options. IT chemotherapy has been treatment of choice but requires placement of ommaya reservoir and has complications. IV treatment would be ideal for the patient but currently used high dose MTX necessitates hospitalization for close monitoring of toxicities. We report the use of IV TT in management of LMC. To our knowledge, this is the largest case series of IV TT as treatment for LMC in MBC patients. TT is well tolerated, can be administered in the ambulatory setting, and has efficacy comparable to other chemotherapeutic agents in treatment of LMC.

Disclosure: All authors have declared no conflicts of interest.