Clinical pharmacology of encapsulated sustained-release cytarabine.
BACKGROUND
The therapeutic effectiveness of chemotherapy is often limited by the inability to sustain cytotoxic concentrations at the tumor site. Cytarabine liposome injection (DepoCyt), a sterile, injectable suspension of the antimetabolite cytarabine, encapsulated into multivesicular, lipid-based particles, has been developed to improve the treatment of neoplastic meningitis (NM) through sustained release of cytarabine.


OBJECTIVE
To review the pharmacokinetics, efficacy, and safety of intrathecal DepoCyt for the treatment of NM secondary to lymphoma or solid tumors.


RESULTS
In preclinical and clinical studies, DepoCyt markedly extended the duration of tumor exposure to cytotoxic concentrations of cytarabine compared with administration of unbound cytarabine. Data from recent clinical studies demonstrate that DepoCyt improves complete response rates among patients with NM secondary to lymphoma. Trends in time to neurologic progression and median survival also favored DepoCyt over unbound cytarabine in these studies. Data have also been presented that suggest that patients with NM secondary to solid tumors benefit more from DepoCyt than from conventional treatment approaches. Chemical arachnoiditis (i.e., headache, fever, nausea, vomiting) was common in patients receiving DepoCyt, however, symptoms were manageable with oral dexamethasone.


CONCLUSIONS
Encapsulation of cytarabine into liposomes for sustained release prolongs tumor exposure to cytotoxic concentrations of cytarabine, which may improve therapeutic efficacy in patients with NM secondary to lymphoma or solid tumors.
Murry
D J
DJ
School of Pharmacy and Pharmacal Sciences, Purdue University, Indianapolis, IN 46202, USA. dmurry@iupui.edu
Blaney
S M
SM
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D003561:Cytarabine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D003692:Delayed-Action Preparations; D006801:Humans
D000964:Antimetabolites, Antineoplastic; D003692:Delayed-Action Preparations; D003561:Cytarabine