ArticleBlood2009
Active oral regimen for elderly adults with newly diagnosed acute myelogenous leukemia: a preclinical and phase 1 trial of the farnesyltransferase inhibitor tipifarnib (R115777, Zarnestra) combined with etoposide.
Article in Blood, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00112853 (A Phase I Trial of Oral Etoposide in Combination With the Farnesyltransferase Inhibitor R115777), which is not on this map. Cited by 32 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase I Trial of Oral Etoposide in Combination With the Farnesyltransferase Inhibitor R115777 (ZARNESTRA, Tipifarnib, NSC #702818, IND #58,359) in Elderly Adults With Newly Diagnosed Acute Myelogenous Leukemia (AML)
Who cites it
32 citing papers in PubMed, 53 citations in OpenAlex.
- Trial
- Trial
- The Role of the Bone Marrow Microenvironment in the Pathogenesis of Acute Myeloid Leukemia.Biomedicines · 2026Review
- Review
- Utilizing Synergistic Potential of Mitochondria-Targeting Drugs for Leukemia Therapy.Frontiers in oncology · 2020Article
- Article
- Acute myeloid leukemia in the elderly: do we know who should be treated and how?Leukemia & lymphoma · 2014Review
- Farnesyltransferase inhibitor tipifarnib inhibits Rheb prenylation and stabilizes Bax in acute myelogenous leukemia cells.Haematologica · 2014Article
- Decitabine in patients with newly diagnosed and relapsed acute myeloid leukemia.Leukemia & lymphoma · 2013Article
- Targeting mutant KRAS for anticancer therapeutics: a review of novel small molecule modulators.Journal of medicinal chemistry · 2013Review
- Pediatric relapsed or refractory leukemia: new pharmacotherapeutic developments and future directions.Drugs · 2013Review
- γ-H2AX foci formation as a pharmacodynamic marker of DNA damage produced by DNA cross-linking agents: results from 2 phase I clinical trials of SJG-136 (SG2000).Clinical cancer research : an official journal of the American Association for Cancer Research · 2013Article
- Targeting of CD34+CD38- cells using Gemtuzumab ozogamicin (Mylotarg) in combination with tipifarnib (Zarnestra) in Acute Myeloid Leukaemia.BMC cancer · 2012Article
- Heterogeneity of molecular markers in chronic myelomonocytic leukemia: a disease associated with several gene alterations.Cellular and molecular life sciences : CMLS · 2012Review
- The clinically relevant pharmacogenomic changes in acute myelogenous leukemia.Pharmacogenomics · 2012Review
- γ-H2AX and other histone post-translational modifications in the clinic.Biochimica et biophysica acta · 2012Review
- Are low-intensity induction strategies better for older patients with acute myeloid leukemia?Leukemia research · 2012Article
- Modulation of anthracycline-induced cytotoxicity by targeting the prenylated proteome in myeloid leukemia cells.Journal of molecular medicine (Berlin, Germany) · 2012Article
- Plumbagin inhibits tumour angiogenesis and tumour growth through the Ras signalling pathway following activation of the VEGF receptor-2.British journal of pharmacology · 2012Article
- Article
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Authors and funding
22 authors at 5 institutions in 1 country.
Funding
Abstract
The farnesyltransferase inhibitor tipifarnib exhibits modest activity against acute myelogenous leukemia. To build on these results, we examined the effect of combining tipifarnib with other agents. Tipifarnib inhibited signaling downstream of the farnesylated small G protein Rheb and synergistically enhanced etoposide-induced antiproliferative effects in lymphohematopoietic cell lines and acute myelogenous leukemia isolates. We subsequently conducted a phase 1 trial of tipifarnib plus etoposide in adults over 70 years of age who were not candidates for conventional therapy. A total of 84 patients (median age, 77 years) received 224 cycles of oral tipifarnib (300-600 mg twice daily for 14 or 21 days) plus oral etoposide (100-200 mg daily on days 1-3 and 8-10). Dose-limiting toxicities occurred with 21-day tipifarnib. Complete remissions were achieved in 16 of 54 (30%) receiving 14-day tipifarnib versus 5 of 30 (17%) receiving 21-day tipifarnib. Complete remissions occurred in 50% of two 14-day tipifarnib cohorts: 3A (tipifarnib 600, etoposide 100) and 8A (tipifarnib 400, etoposide 200). In vivo, tipifarnib plus etoposide decreased ribosomal S6 protein phosphorylation and increased histone H2AX phosphorylation and apoptosis. Tipifarnib plus etoposide is a promising orally bioavailable regimen that warrants further evaluation in elderly adults who are not candidates for conventional induction chemotherapy. These clinical studies are registered at www.clinicaltrials.gov as #NCT00112853.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.