Trial reportBritish journal of cancer1999
Phase I and pharmacokinetic study of the topoisomerase II catalytic inhibitor fostriecin.
Trial report in British journal of cancer, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 55 citations in OpenAlex.
- Phase I and pharmacokinetic study of fostriecin given as an intravenous bolus daily for five consecutive days.Investigational new drugs · 2004Trial
- Covalent warhead assembly in fostriecin biosynthesis involves malonylation-lactonisation by a bifunctional thioesterase and enzymatic demalonylation.Nature communications · 2026Article
- Concise Synthesis of Fostriecin and Analogs through Late-Stage Chemoenzymatic Installation of Their Key Pharmacophores.Journal of the American Chemical Society · 2025Article
- Formal Synthesis of Fostriecin via Asymmetric Alcohol-Mediated Carbonyl Allylation.Organic letters · 2025Article
- Strategies for Solubility and Bioavailability Enhancement and Toxicity Reduction of Norcantharidin.Molecules (Basel, Switzerland) · 2022Review
- Total and Formal Syntheses of Fostriecin.Organic chemistry frontiers : an international journal of organic chemistry · 2020Article
- Total Synthesis and Structural Validation of Phosdiecin A via Asymmetric Alcohol-Mediated Carbonyl Reductive Coupling.Journal of the American Chemical Society · 2019Article
- Synthetic Strategies Employed for the Construction of Fostriecin and Related Natural Products.Chemical reviews · 2016Review
- Development and validation of a robust and sensitive assay for the discovery of selective inhibitors for serine/threonine protein phosphatases PP1α (PPP1C) and PP5 (PPP5C).Assay and drug development technologies · 2014Article
- Suppression of Ser/Thr phosphatase 4 (PP4C/PPP4C) mimics a novel post-mitotic action of fostriecin, producing mitotic slippage followed by tetraploid cell death.Molecular cancer research : MCR · 2013Article
- Total synthesis and evaluation of phostriecin and key structural analogues.The Journal of organic chemistry · 2010Article
- Total synthesis of fostriecin: via a regio- and stereoselective polyene hydration, oxidation, and hydroboration sequence.Organic letters · 2010Article
- Rubratoxin A specifically and potently inhibits protein phosphatase 2A and suppresses cancer metastasis.Cancer science · 2010Article
- Anti-proliferative effects of simocyclinone D8 (SD8), a novel catalytic inhibitor of topoisomerase II.Investigational new drugs · 2010Article
- Genetic manipulation of the biosynthetic process leading to phoslactomycins, potent protein phosphatase 2A inhibitors.Journal of industrial microbiology & biotechnology · 2006Review
- The role of serine/threonine protein phosphatases in exocytosis.The Biochemical journal · 2003Review
- Protein phosphatase 2A enhances activation of human immunodeficiency virus type 1 by phorbol myristate acetate.Journal of virology · 2003Article
- Anticancer activity and protein phosphatase 1 and 2A inhibition of a new generation of cantharidin analogues.Investigational new drugs · 2002Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We conducted a phase I and pharmacokinetic study of the topoisomerase II catalytic inhibitor fostriecin. Fostriecin was administered intravenously over 60 min on days 1-5 at 4-week intervals. Dose was escalated from 2 mg m(-2) day(-1) to 20 mg m(-2) day(-1) in 20 patients. Drug pharmacokinetics was analysed with high performance liquid chromatography with UV-detection. Plasma collected during drug administration was tested in vitro for growth inhibition of a teniposide-resistant small-cell lung cancer (SCLC) cell line. The predominant toxicities were elevated liver transaminases (maximum common toxicity criteria (CTC) grade 4) and serum creatinine (maximum CTC grade 2). These showed only a limited increase with increasing doses, often recovered during drug administration and were fully reversible. Duration of elevated alanine-amino transferase (ALT) was dose-limiting in one patient at 20 mg m(-2). Other frequent toxicities were grade 1-2 nausea/vomiting, fever and mild fatigue. Mean fostriecin plasma half-life was 0.36 h (initial; 95% CI, 0-0.76 h) and 1.51 h (terminal; 95% CI, 0.41-2.61 h). A metabolite, most probably dephosphorylated fostriecin, was detected in plasma and urine. No tumour responses were observed, but the plasma concentrations reached in the patients were insufficient to induce significant growth inhibition in vitro. The maximum tolerated dose (MTD) has not been reached, because drug supply was stopped at the 20 mg m(-2) dose level. However, further escalation seems possible and is warranted to achieve potentially effective drug levels. Fostriecin has a short plasma half-life and longer duration of infusion should be considered.
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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.