Tipifarnib: Farnesyl transferase inhibition at a crossroads

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Tipifarnib is an oral nonpeptidomimetic farnesyl transferase inhibitor developed to inhibit a variety of farnesylated targets potentially relevant to the therapy of various malignancies. The agent has, thus far, been tested in a wide array of both solid tumors and myeloid malignancies. Phase I trials have demonstrated that tipifarnib is best given in a twice-daily fashion in doses of 600-1200 mg/day to avoid significant neuropathy, fatigue and myelosuppression. Subsequent trials demonstrated that pauses in therapy (with staccato dosing schedules) seem to increase tolerability without a clear decrease in efficacy. Phase II and III trials of tipifarnib as monotherapy for breast, colorectal, lung (both non-small cell and small cell), brain, pancreatic and urothelial cancers have all been disappointing. Combination trials of tipifarnib with cytotoxic, hormonal or biological therapies are ongoing. Tipifarnib has displayed the most interesting activity in the myeloid malignancies of myelodysplastic syndrome, myelofibrosis with myeloid metaplasia and elderly/high-risk acute myeloid leukemia. Overall clinical response rates of approximately 20-30% have been reported in myelodysplastic syndrome and acute myeloid leukemia patients who have few alternative therapeutic options. US FDA approval for tipifarnib awaits results of subsequent Phase III trials of the agent in elderly acute leukemia.

Original languageEnglish (US)
Pages (from-to)313-319
Number of pages7
JournalExpert Review of Anticancer Therapy
Volume6
Issue number3
DOIs
StatePublished - Mar 1 2006
Externally publishedYes

Fingerprint

tipifarnib
Transferases
Myelodysplastic Syndromes
Acute Myeloid Leukemia
Neoplasms
Primary Myelofibrosis
Biological Therapy
Pancreatic Neoplasms
Fatigue
Appointments and Schedules
Leukemia
Breast
Therapeutics
Lung
Brain

Keywords

  • Acute myeloid leukemia
  • Farnesyl transferase inhibitor
  • Myelofibrosis
  • r115777
  • Tififarnib

ASJC Scopus subject areas

  • Oncology
  • Pharmacology (medical)

Cite this

Tipifarnib : Farnesyl transferase inhibition at a crossroads. / Mesa, Ruben.

In: Expert Review of Anticancer Therapy, Vol. 6, No. 3, 01.03.2006, p. 313-319.

Research output: Contribution to journalArticle

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