A phase I, pharmacokinetic (PK), and pharmacodynamic (PD) study of the farnesyl transferase inhibitor (FTI) R115777 in combination with weekly paclitaxel in patients (pts) with advanced solid cancers

Patnaik, Amita; Mita, Akira; Izbicka, Elzbieta; Carrizales, Gilbert; Howes, Angela; Troenaru, M.; Tolcher, A. W.; Zhang, S.; Berg, Kasper Drimer; Rowinsky, Eric K.

doi:10.1200/jco.2004.22.14_suppl.3136

JCO

2004

DOI: 10.1200/jco.2004.22.14_suppl.3136

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A phase I, pharmacokinetic (PK), and pharmacodynamic (PD) study of the farnesyl transferase inhibitor (FTI) R115777 in combination with weekly paclitaxel in patients (pts) with advanced solid cancers

Amita Patnaik

Akira Mita

Elzbieta Izbicka

et al.

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Tipifarnib: farnesyl transferase inhibition at a crossroads

Mesa¹

2006

Expert Review of Anticancer Therapy

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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.

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Tipifarnib: farnesyl transferase inhibition at a crossroads

Mesa¹

2006

Expert Review of Anticancer Therapy

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A phase I, pharmacokinetic (PK), and pharmacodynamic (PD) study of the farnesyl transferase inhibitor (FTI) R115777 in combination with weekly paclitaxel in patients (pts) with advanced solid cancers

Cited by 1 publication

References 0 publications

Tipifarnib: farnesyl transferase inhibition at a crossroads

Tipifarnib: farnesyl transferase inhibition at a crossroads

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