Clinical pharmacology of encapsulated sustained-release cytarabine

D. J. Murry, S. M. Blaney

Research output: Contribution to journalReview article

55 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1173-1178
Number of pages6
JournalAnnals of Pharmacotherapy
Volume34
Issue number10
DOIs
StatePublished - 2000

Keywords

  • DepoFoam technology
  • Liposome-encapsulated
  • Lymphomatous meningitis
  • Neoplastic meningitis
  • Sustained-release cytarabine

ASJC Scopus subject areas

  • Pharmacology (medical)

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