Trial reportBritish journal of cancer1999
Dose escalation and pharmacokinetic study of a humanized anti-HER2 monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast cancer.
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 30 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 113 citations in OpenAlex.
- Influence of tumour burden on trastuzumab pharmacokinetics in HER2 positive non-metastatic breast cancer.British journal of clinical pharmacology · 2016Trial
- Article
- Pharmacokinetics of trastuzumab and its efficacy and safety in HER2-positive cancer patients.Cancer chemotherapy and pharmacology · 2024Review
- Mechanistic Modeling of Intrathecal Chemotherapy Pharmacokinetics in the Human Central Nervous System.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- The quest for balance between capturing data and model complexity: A quantitative clinical pharmacology approach applied to monoclonal antibodies.CPT: pharmacometrics & systems pharmacology · 2023Article
- Review
- Potential and pitfalls ofEJNMMI research · 2021Article
- Is weight-based IV dosing of trastuzumab preferable to SC fixed-dose in some patients? A systematic scoping review.Breast (Edinburgh, Scotland) · 2021Article
- Phase I study of TrasGEX, a glyco-optimised anti-HER2 monoclonal antibody, in patients with HER2-positive solid tumours.ESMO open · 2018Article
- Fixed Dosing of Monoclonal Antibodies in Oncology.The oncologist · 2017Review
- Population PBPK modelling of trastuzumab: a framework for quantifying and predicting inter-individual variability.Journal of pharmacokinetics and pharmacodynamics · 2017Article
- Unveiling changes in the landscape of patient populations in cancer early drug development.Oncotarget · 2017Review
- Physiologically-based pharmacokinetic modeling to predict the clinical pharmacokinetics of monoclonal antibodies.Journal of pharmacokinetics and pharmacodynamics · 2016Article
- Potential Sources of Inter-Subject Variability in Monoclonal Antibody Pharmacokinetics.Clinical pharmacokinetics · 2016Review
- Phase 1 combination study of eribulin mesylate with trastuzumab for advanced or recurrent human epidermal growth factor receptor 2 positive breast cancer.Investigational new drugs · 2015Article
- Quantitative measurement of the target-mediated internalization kinetics of biopharmaceuticals.Pharmaceutical research · 2015Article
- A phase 1 study of a heterologous prime-boost vaccination involving a truncated HER2 sequence in patients with HER2-expressing breast cancer.Molecular therapy. Methods & clinical development · 2015Article
- Incorporating target-mediated drug disposition in a minimal physiologically-based pharmacokinetic model for monoclonal antibodies.Journal of pharmacokinetics and pharmacodynamics · 2014Article
- Determining the optimal dose in the development of anticancer agents.Nature reviews. Clinical oncology · 2014Review
- Incorporating Target Shedding Into a Minimal PBPK-TMDD Model for Monoclonal Antibodies.CPT: pharmacometrics & systems pharmacology · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We conducted a phase I pharmacokinetic dose escalation study of a recombinant humanized anti-p185HER2 monoclonal antibody (MKC-454) in 18 patients with metastatic breast cancer refractory to chemotherapy. Three or six patients at each dose level received 1, 2, 4 and 8 mg kg(-1) of MKC-454 as 90-min intravenous infusions. The first dose was followed in 3 weeks by nine weekly doses. Target trough serum concentration has been set at 10 microg ml(-1) based on in vitro observations. The mean value of minimum trough serum concentrations at each dose level were 3.58 +/- 0.63, 6.53 +/- 5.26, 40.2 +/- 7.12 and 87.9 +/- 23.5 microg ml(-1) respectively. At 2 mg kg(-1), although minimum trough serum concentrations were lower than the target trough concentration with a wide range of variation, trough concentrations increased and exceeded the target concentration, as administrations were repeated weekly. Finally 2 mg kg(-1) was considered to be sufficient to achieve the target trough concentration by the weekly dosing regimen. One patient receiving 1 mg kg(-1) had grade 3 fever, one at the 1 mg kg(-1) level had severe fatigue defined as grade 3, and one at 8 mg kg(-1) had severe bone pain of grade 3. No antibodies against MKC-454 were detected in any patients. Objective tumour responses were observed in two patients; one receiving 4 mg kg(-1) had a partial response in lung metastases and the other receiving 8 mg kg(-1) had a complete response in soft tissue metastases. These results indicate that MKC-454 is well tolerated and effective in patients with refractory metastatic breast cancers overexpressing the HER2 proto-oncogene. Further evaluation of this agent with 2-4 mg kg(-1) weekly intravenous infusion is warranted.
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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.