Preclinical, pharmacologic, and phase I studies of gemcitabine.

Anna Maria Storniolo, S. R. Allerheiligen, H. L. Pearce

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

Gemcitabine (2',2'-difluorodeoxycytidine) is a novel nucleoside analogue that exerts its antitumor activity via multiple mechanisms of action. These include (1) incorporation of gemcitabine into replicating DNA, which inhibits DNA replication and cell growth, (2) masked DNA chain termination, and (3) several self-potentiation mechanisms that serve to increase intracellular levels of the active compound. Preclinical experiments in various cell lines and animal models demonstrate a broad range of cytotoxic activity. Pharmacokinetic studies of gemcitabine delivered by its usual schedule (30-minute weekly infusion) reveal a short plasma half-life and a high clearance into central and peripheral compartments (two-compartment model). The drug is excreted almost completely in the urine as the parent compound and primary metabolite (difluorodeoxyuridine). Phase I trials demonstrate that pharmacokinetics are schedule dependent and that, in general, gemcitabine is well tolerated. Dose-limiting toxicities are primarily myelosuppression, with other toxicities being rash, flu-like symptoms, and transient elevations in liver function tests.

Original languageEnglish (US)
JournalSeminars in Oncology
Volume24
Issue number2 Suppl 7
StatePublished - Apr 1997

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gemcitabine
Appointments and Schedules
Pharmacokinetics
Liver Function Tests
DNA
Exanthema
DNA Replication
Nucleosides
Half-Life
Animal Models
Urine
Cell Line
Growth

ASJC Scopus subject areas

  • Oncology

Cite this

Storniolo, A. M., Allerheiligen, S. R., & Pearce, H. L. (1997). Preclinical, pharmacologic, and phase I studies of gemcitabine. Seminars in Oncology, 24(2 Suppl 7).

Preclinical, pharmacologic, and phase I studies of gemcitabine. / Storniolo, Anna Maria; Allerheiligen, S. R.; Pearce, H. L.

In: Seminars in Oncology, Vol. 24, No. 2 Suppl 7, 04.1997.

Research output: Contribution to journalArticle

Storniolo, AM, Allerheiligen, SR & Pearce, HL 1997, 'Preclinical, pharmacologic, and phase I studies of gemcitabine.', Seminars in Oncology, vol. 24, no. 2 Suppl 7.
Storniolo, Anna Maria ; Allerheiligen, S. R. ; Pearce, H. L. / Preclinical, pharmacologic, and phase I studies of gemcitabine. In: Seminars in Oncology. 1997 ; Vol. 24, No. 2 Suppl 7.
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