Trial reportInvestigational new drugs2012
Phase I/II multicenter study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of AZD4877 in patients with refractory acute myeloid leukemia.
Trial report in Investigational new drugs, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00486265 (A Phase I/II, Open-Label, Multi-Center, Two-Part Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of AZD4877 Administered on Days 1, 2 and 3 in Adult Patients With Recurrent or Refractory Acute Myelogenous Leukemia), which is not on this map. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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/II, Open-Label, Multi-Center, Two-Part Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of AZD4877 Administered on Days 1, 2 and 3 in Adult Patients With Recurrent or Refractory Acute Myelogenous Leukemia (AML) Excluding Promyelocytic Leukemia
Who cites it
26 citing papers in PubMed, 51 citations in OpenAlex.
- Phase II study to assess the efficacy, safety and tolerability of the mitotic spindle kinesin inhibitor AZD4877 in patients with recurrent advanced urothelial cancer.Investigational new drugs · 2013Trial
- Kinesin Spindle Protein (KIF11) in Mitosis and Cancer.International journal of molecular sciences · 2025Review
- The role of kinesin superfamily proteins in hepatocellular carcinoma.Medical oncology (Northwood, London, England) · 2024Review
- CENP-E Inhibition Induces Chromosomal Instability and Synergizes with Diverse Microtubule-Targeting Agents in Breast Cancer.Cancer research · 2024Article
- The two sides of chromosomal instability: drivers and brakes in cancer.Signal transduction and targeted therapy · 2024Review
- Diverse microtubule-targeted anticancer agents kill cells by inducing chromosome missegregation on multipolar spindles.PLoS biology · 2023Article
- Optical Control of Mitosis with a Photoswitchable Eg5 Inhibitor.Angewandte Chemie (International ed. in English) · 2022Article
- Is more better? An analysis of toxicity and response outcomes from dose-finding clinical trials in cancer.BMC cancer · 2021Article
- Article
- Second-Generation Antimitotics in Cancer Clinical Trials.Pharmaceutics · 2021Review
- KIF11 is upregulated in colorectal cancer and silencing of it impairs tumor growth and sensitizes colorectal cancer cells to oxaliplatin via p53/GSK3β signaling.Journal of Cancer · 2021Article
- Would the Recommended Dose Have Been Different Using Novel Dose-Finding Designs? Comparing Dose-Finding Designs in Published Trials.JCO precision oncology · 2021Article
- Mitotic Poisons in Research and Medicine.Molecules (Basel, Switzerland) · 2020Review
- Kinesin family members KIF2C/4A/10/11/14/18B/20A/23 predict poor prognosis and promote cell proliferation in hepatocellular carcinoma.American journal of translational research · 2020Article
- High kinesin family member 18A expression correlates with poor prognosis in primary lung adenocarcinoma.Thoracic cancer · 2019Article
- Dual inhibition of Kif15 by oxindole and quinazolinedione chemical probes.Bioorganic & medicinal chemistry letters · 2019Article
- A New Way to Treat Brain Tumors: Targeting Proteins Coded by Microcephaly Genes?: Brain tumors and microcephaly arise from opposing derangements regulating progenitor growth. Drivers of microcephaly could be attractive brain tumor targets.BioEssays : news and reviews in molecular, cellular and developmental biology · 2018Review
- KIFC1: a promising chemotherapy target for cancer treatment?Oncotarget · 2016Review
- Article
- Aurea mediocritas: the importance of a balanced genome.Cold Spring Harbor perspectives in biology · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
Abstract
Eg5 (kinesin spindle protein) is a microtubule motor protein, essential for centrosome separation during mitosis. This Phase I/II, open-label, multicenter, two-part study investigated AZD4877, a potent Eg5 inhibitor, in patients with acute myeloid leukemia. Primary objectives were to determine the maximum tolerated dose (MTD) (part A), assess efficacy (part B) and determine the pharmacokinetic profile (parts A and B). Secondary objectives included assessment of safety and tolerability. AZD4877 was administered at a range of doses (2, 4, 7, 10, 13, 16 and 18 mg/day) as a 1-hour intravenous infusion on three consecutive days of a continuous 2-week schedule. The MTD in part A was defined as 16 mg/day based on dose-limiting stomatitis at 16 and 18 mg/day, hyperbilirubinemia at 16 mg/day and palmar-plantar erythrodysesthesia syndrome at 18 mg/day. Systemic exposure to AZD4877 generally increased with increasing dose whereas half-life was not dose dependent. No evaluable patients experienced a complete remission (CR) or CR with incomplete blood count recovery (CRi), demonstrating no evidence of AZD4877 efficacy in this population. Evidence of monoasters in all but the 4 mg/day dose group provided proof of mechanism for AZD4877. This study was terminated due to lack of efficacy. (ClinicalTrials.gov identifier NCT00486265).
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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.