Phase 2 study of intrathecal, long‐acting liposomal cytarabine in the prophylaxis of lymphomatous meningitis in human immunodeficiency virus‐related non‐Hodgkin lymphoma

Abstract

BACKGROUND:Patients with aggressive non-Hodgkin lymphoma (NHL) develop central nervous system (CNS) progression or recurrence during the course of their disease. Patients with human immunodeficiency virus (HIV)-NHL often develop CNS progression despite the use of prophylaxis. Liposomal cytarabine (DepoCyte) has shown activity in lymphomatous meningitis, but there are limited data for prophylaxis. METHODS: Between May 2006 and December 2008, a phase 2 study of intrathecal liposomal cytarabine was performed at the dose of 50 mg in 30 patients with HIV-NHL, with the aim of evaluating feasibility and activity for prophylaxis. RESULTS: Liposomal cytarabine was well tolerated, with headache grade I to III being the most frequent side effect in 40% of patients. With a median followup of 10.5 months, only 1 (3%) patient developed a combined systemic and meningeal recurrence. The use of liposomal cytarabine allowed significant reduction of the number of lumbar injections in comparison to the standard schedules (around 50%), improving the quality of life of patients and reducing the professional exposure risk. CONCLUSIONS: In this first study on prophylaxis of lymphomatous meningitis in HIV-NHL, liposomal cytarabine seems safe and active; it reduces by approximately 50% the number of lumbar punctures, and exposure risk for health staff as well.

Nanomedicinal products: a survey on specific toxicity and side effects

“…13,15,37,41 Nonetheless, the nanoformulation may reduce the overall toxicity of a drug, the severity of the side effects, or better suit specific treatments of patients. We wished to evaluate whether specific end points of toxicity require specific or further attention with respect to NMPs.…”

“…These examples of a shift in toxicological profile due to changes in the pharmacokinetics of drugs could still reduce the overall toxicity of a drug, the severity of the side effects, or better suit specific patients. 12 A liposomal formulation of cytarabine (DepoCyt ® ) has been reported to cause the same efficacy but less toxicity in the treatment of specific cancers compared to unbound cytarabine, 13,14 and a liposomal formulation of daunorubicin citrate (DaunoXome ® ) is associated with reduced cardiotoxicity compared to conventional daunorubicin. 15 In addition to the six liposomal encapsulations, other structures of nanocarriers are applied, such as docetaxel solubilized by micelle formation with polysorbate 80 (Taxotere ® ), proteinbound pemetrexed (Alimta ® ), or albumin-bound paclitaxel (Abraxane ® ).…”

“…13,41 Liposomal cytarabine is a slowrelease cytarabine formulation that encapsulates the drug in spherical multivesicular particles resulting in a gradual …”

“…13,14 However, the lower toxicity of liposomal cytarabine could not be confirmed based on the comparison of the types or frequencies of the side effects when compared to conventional cytarabine.…”

Flow Cytometry Approach for the Identification of Liposomal Cytarabine Toxicity

“…It is being used for treatment and prophylaxis of CNS involvement in many hematological malignancies, mainly ALL and lymphomas [9,10], but also as therapy for solid tumor neoplastic meningitis [11]. Side effects with LC are not common [12,13], but moderate to severe neurotoxicity has been reported [14][15][16][17]. Central (headache, vertigo, seizures, intracranial hypertension, etc...) or peripheral (cauda equina syndrome, radiculopathy) neurological symptoms may develop, but they are not specific and infections or cerebrovascular and metabolic diseases may also be responsible.…”