title: Neurotoxicity of intra-CSF liposomal cytarabine (DepoCyt) administered for the treatment of leptomeningeal metastases: a retrospective case series.
abstract: Treatment of leptomeningeal metastasis (LMD) remains challenging due to advanced systemic disease at presentation and limited treatment options. All patients underwent standard pre-treatment LMD evaluation including CSF assessment (cytology or flow cytometry), brain and spine MR imaging, and radioisotope CSF flow study. DepoCyt (liposomal cytarabine) was administered intraventricularly (n = 80) or intralumbar (n = 40) at 50 mg every 2 weeks × 4 and then every 4 weeks × 6 in responding patients. Dexamethasone (4 mg orally twice per day × 5 days) was co-administered with each DepoCyt treatment. Patients were seen with each DepoCyt treatment and assessed for toxicity. 120 adult patients [median age 51 years (range 33-68)] with LMD were treated with DepoCyt. DepoCyt Common Toxicity Criteria ≥ Grade 3 neurotoxicity was seen in 60 cycles (11.5 %) in 28 patients (23.3 %). Toxicity included bacterial meningitis (3.75 % of ventricular treatments: 0 % of lumbar treatments); chemical meningitis (17.5:15 %); communicating hydrocephalus (3.75:5 %); conus medullaris/cauda equina syndrome (5:5 %); decreased visual acuity (5:2.5 %); encephalopathy (5:5 %); leukoencephalopathy (7.5:2.5 %); myelopathy (2.5:2.5 %); radiculopathy (1.25:5 %); and seizures (1.25:2.5 %). Distribution of toxicity was similar regardless of route of administration (ventricular vs. lumbar). Toxicities were transient in 34 episodes (57 %) and permanent in 26 (43 %). There were no treatment-related deaths however 20 treatment-related toxicities (32.2 %) required hospitalization. In this retrospective case series, DepoCyt is generally well tolerated however a subset of patients (12.5 %) not easily identified pre-treatment, develop serious treatment-related neurological complications that may be persistent and impact quality of life.
authors.affiliation: Department of Neurology and Neurosurgery, University of Washington, Seattle, WA 98109, USA. chambemc@u.washington.edu
authors.forename: Marc C
authors.initials: MC
authors.lastname: Chamberlain
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects*; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007278:Injections, Spinal; D008081:Liposomes; D008279:Magnetic Resonance Imaging; D008297:Male; D008577:Meningeal Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008875:Middle Aged; D009367:Neoplasm Staging; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D020258:Neurotoxicity Syndromes / Q000209:etiology; D011379:Prognosis; D011446:Prospective Studies; D012189:Retrospective Studies
chemical_list: D000964:Antimetabolites, Antineoplastic; D008081:Liposomes; D003561:Cytarabine