ArticleCancer chemotherapy and pharmacology2012
Phase I dose escalation study of KOS-1584, a novel epothilone, in patients with advanced solid tumors.
Article in Cancer chemotherapy and pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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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.
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Who cites it
7 citing papers in PubMed, 17 citations in OpenAlex.
- Review
- Resistance to anti-tubulin agents: From vinca alkaloids to epothilones.Cancer drug resistance (Alhambra, Calif.) · 2019Review
- Biosensor-aided high-throughput screening of hyper-producing cells for malonyl-CoA-derived products.Microbial cell factories · 2017Article
- Recent Advances in the Development of Antineoplastic Agents Derived from Natural Products.Drugs · 2015Review
- Quantitative method for the determination of iso-fludelone (KOS-1803) in human plasma by LC-MS/MS.Journal of pharmaceutical and biomedical analysis · 2014Article
- Epothilones: From discovery to clinical trials.Current topics in medicinal chemistry · 2014Review
- Phase I clinical, pharmacokinetic, and pharmacodynamic study of KOS-862 (Epothilone D) in patients with advanced solid tumors and lymphoma.Investigational new drugs · 2012Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
purposeFirst-in-man study of KOS-1584, a second generation epothilone.
methodsPatients with advanced solid malignancies received KOS-1584 every 3 weeks until disease progression. Using a modified Fibonacci dose escalation scheme, one patient was enrolled at each dose level until the first instance of grade 2 toxicity. Thereafter, a standard 3 + 3 design was utilized.
resultsSixty-six patients in 14 cohorts were dosed from 0.8 to 48 mg/m(2). Diarrhea, arthralgias, and encephalopathy were dose-limiting toxicities (DLTs) at doses ≥36 mg/m(2). At the recommended phase II dose (RP2D), the most common adverse effects were peripheral neuropathy (low grade), fatigue, arthralgias/myalgias, and diarrhea (31, 6%). The incidence of neutropenia was low. The overall clearance, volume of distribution, and half-life of KOS-1584 were 11 ± 6.17 L/h/m(2), 327 ± 161 L/m(2), and 21.9 ± 8.75 h, respectively. The half-life for the seco-metabolite (KOS-1891) was 29.6 ± 13.8 h. KOS-1584 exhibited linear pharmacokinetics. A dose-dependent increase in microtubulin bundle formation was observed at doses ≥27 mg/m(2). Two patients achieved partial responses and 24 patients had stable disease (SD).
conclusionsThe RP2D of KOS-1584 is 36 mg/m(2). The lack of severe neurologic toxicity, diarrhea, neutropenia, or hypersensitivity reactions; favorable pharmacokinetic profile; and early evidence of activity support further evaluation.
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