Trial reportBritish journal of clinical pharmacology2002
Pharmacokinetics and pharmacodynamics of combination chemotherapy with paclitaxel and epirubicin in breast cancer patients.
Trial report in British journal of clinical pharmacology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Administration sequences in single-day chemotherapy regimens for breast cancer: a comprehensive review from a practical perspective.Frontiers in oncology · 2024Pooled it
- Multicenter randomized phase III trial of epirubicin plus paclitaxel vs epirubicin followed by paclitaxel in metastatic breast cancer patients: focus on cardiac safety.British journal of cancer · 2004Trial
- Characterization of anticancer therapy-induced microvascular dysfunction in patients with breast cancer supports targeted intervention.JCI insight · 2025Article
- Extracellular vesicles as the next-generation modulators of pharmacokinetics and pharmacodynamics of medications and their potential as adjuvant therapeutics.Clinical and translational medicine · 2024Review
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- Conquering Cancer Multi-Drug Resistance Using Curcumin and Cisplatin Prodrug-Encapsulated Mesoporous Silica Nanoparticles for Synergistic Chemo- and Photodynamic Therapies.Nanomaterials (Basel, Switzerland) · 2022Article
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- Primary Culture of Undifferentiated Pleomorphic Sarcoma: Molecular Characterization and Response to Anticancer Agents.International journal of molecular sciences · 2017Article
- Myxofibrosarcoma primary cultures: molecular and pharmacological profile.Therapeutic advances in medical oncology · 2017Article
- A Prospective Study to Evaluate the Effect of Paclitaxel on Cardiac Ejection Fraction.Breast care (Basel, Switzerland) · 2017Article
- Activity of Eribulin in a Primary Culture of Well-Differentiated/Dedifferentiated Adipocytic Sarcoma.Molecules (Basel, Switzerland) · 2016Article
- Article
- Pharmacological effects of formulation vehicles : implications for cancer chemotherapy.Clinical pharmacokinetics · 2003Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsTo investigate the pharmacokinetics and pharmacodynamics of epirubicin and paclitaxel in combination, as well as the effects of paclitaxel and its vehicle Cremophor EL on epirubicin metabolism.
methodsTwenty-seven female patients with metastatic breast cancer received epirubicin 90 mg m-2 i.v. followed 15 min or 30 h later by a 3 h i.v. infusion of paclitaxel 175, 200 and 225 mg m-2. Plasma concentrations of paclitaxel, epirubicin and epirubicinol were measured and the relationship between neutropenia and drug pharmacokinetics was evaluated using a sigmoid maximum effect (Emax) model. Finally, the influence of paclitaxel and Cremophor EL on epirubicin metabolism by whole blood was examined.
resultsAn increase in epirubicinol plasma concentrations occurred after the start of the paclitaxel infusion, resulting in a significant increase in the area under the plasma concentration-time curve (AUC) of epirubicinol (+0.5 micromol l-1 h [95% CI for the difference: 0.29, 0.71],+0.66 micromol l-1 h [95% CI for the difference: 0.47, 0.85] and +0.82 micromol l-1 h [95% CI for the difference: 0.53, 1.11] at paclitaxel doses of 175, 200 and 225 mg m-2, respectively), compared with epirubicin followed by paclitaxel 30 h later (0.61+/-0.1 micromol l-1 h). A significant increase in epirubicin AUC (+0.74 micromol l-1 h [95% CI for the difference: 0.14, 1.34] and +1.09 micromol l-1 h [95% CI for the difference: 0.44, 1.74]) and decrease in drug clearance (CLTB) (-25.35 l h-1 m-2[95% CI for the difference: -50.18, -0.52] and -35.9 l h-1 m-2[95% CI for the difference -63,4,-8,36]) occurred in combination with paclitaxel 200 and 225 mg m-2 with respect to the AUC (3.16+/-0.6 micromol l-1 h) and CLTB (74.4+/-28.4 l h-1 m-2) of epirubicin followed by paclitaxel 30 h later. An Emax relationship was observed between neutropaenia and the time over which paclitaxel plasma concentrations were equal to or greater than 0.1 micromol l-1 (tC0.1). The tC0.1 value predicted to yield a 50% decrease in neutrophil count was 7.7 h. Finally, Cremophor EL markedly inhibited the metabolism of epirubicin to epirubicinol in whole blood.
conclusionsPaclitaxel/Cremophor EL affects the disposition of epirubicinol and epirubicin. Furthermore, the slope factor of the Emax relationship between neutropenia and tC0.1 of paclitaxel suggests that the drugs might also interact at the pharmacodynamic level.
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