Histamine‐2 (H <sub>2</sub>) antagonists can be safely removed from standard paclitaxel premedication regimens

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Abstract

Aims

The aim of this study is to investigate the rates of hypersensitivity reactions (HSRs) in patients receiving paclitaxel chemotherapy, with and without a histamine‐2 (H ₂) antagonists.

Method

This prospective, multi‐centre, cohort study compared patients receiving paclitaxel treated with premedication regimens containing chlorphenamine, dexamethasone and an H ₂ antagonist vs patients treated without an H ₂ antagonist. Rates of HSRs were described and logistic multivariable regression was used to investigate any associations with H ₂ antagonist treatment, adjusting for confounding variables.

Results

A total of 1043 individuals were included in the study; of these, 638 (61%) patients received an H ₂ antagonist and 405 (49%) were not given an H ₂ antagonist. Incidence of HSR in the cohort treated with H ₂ antagonists was 11.31% ( n = 70) vs 9.86% ( n = 41) in the cohort without. There was no statistically significant difference between the rates of HSR observed in those receiving and not receiving an H ₂ antagonist (odds ratio 1.04, 95% CI 0.65, 1.66, P = .9).

Conclusions

Results presented within the study are consistent with other recently published evidence to suggest that H ₂ antagonists do not confer any advantage as part of premedication regimens in reducing the incidence of HSR in patients treated with paclitaxel.

Related collections

Most cited references 26

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THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: G protein-coupled receptors.

Stephen Ph Alexander, Arthur Christopoulos, Anthony P. Davenport … (2021)

The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15538. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.

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Jeffrey B. Jones, Glynn Baker, D Trump … (1990)

Taxol is an antitumor agent in clinical trial that has been shown to have activity against advanced ovarian carcinoma and melanoma. Hypersensitivity reactions (HSRs) have been one of the toxicities observed with administration of this drug. Of 301 patients treated, 32 patients have had definite (27 patients) or possible (five patients) hypersensitivity reactions to taxol. All but one patient had the reaction from the first or second exposure to this agent. Reactions occurred at a variety of doses and were characterized most frequently by dyspnea, hypotension, bronchospasm, urticaria, and erythematous rashes. Thirteen (41%) patients had received premedication designed to prevent such toxicity; nevertheless, they sustained HSRs. Prolonging the drug infusion appears to have somewhat reduced, but not obviated, the risk of HSRs. The cause (taxol itself or its excipient Cremophor EL; Badische Anilin und Soda-Fabrik AG [BASF], Ludwigshafen, Federal Republic of Germany) and the mechanism of these reactions to taxol are unknown. We provide guidelines to prevent or minimize such toxicity and treat reactions if they still occur.

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Antonio Wolff, J Sparano, George Sledge … (2008)

We compared the efficacy of two different taxanes, docetaxel and paclitaxel, given either weekly or every 3 weeks, in the adjuvant treatment of breast cancer. We enrolled 4950 women with axillary lymph node-positive or high-risk, lymph node-negative breast cancer. After randomization, all patients first received 4 cycles of intravenous doxorubicin and cyclophosphamide at 3-week intervals and were then assigned to intravenous paclitaxel or docetaxel given at 3-week intervals for 4 cycles or at 1-week intervals for 12 cycles. The primary end point was disease-free survival. As compared with patients receiving standard therapy (paclitaxel every 3 weeks), the odds ratio for disease-free survival was 1.27 among those receiving weekly paclitaxel (P=0.006), 1.23 among those receiving docetaxel every 3 weeks (P=0.02), and 1.09 among those receiving weekly docetaxel (P=0.29) (with an odds ratio >1 favoring the groups receiving experimental therapy). As compared with standard therapy, weekly paclitaxel was also associated with improved survival (odds ratio, 1.32; P=0.01). An exploratory analysis of a subgroup of patients whose tumors expressed no human epidermal growth factor receptor type 2 protein found similar improvements in disease-free and overall survival with weekly paclitaxel treatment, regardless of hormone-receptor expression. Grade 2, 3, or 4 neuropathy was more frequent with weekly paclitaxel than with paclitaxel every 3 weeks (27% vs. 20%). Weekly paclitaxel after standard adjuvant chemotherapy with doxorubicin and cyclophosphamide improves disease-free and overall survival in women with breast cancer. (ClinicalTrials.gov number, NCT00004125 [ClinicalTrials.gov].). Copyright 2008 Massachusetts Medical Society.

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Author and article information

Contributors

Calum Polwart:

ORCID: https://orcid.org/0000-0002-4774-6366

calum.polwart@nhs.net

Pinkie Chambers:

ORCID: https://orcid.org/0000-0002-6669-9411

p.chambers@ucl.ac.uk

Journal

Journal ID (nlm-ta): Br J Clin Pharmacol

Journal ID (iso-abbrev): Br J Clin Pharmacol

Journal ID (doi): 10.1111/(ISSN)1365-2125

Journal ID (publisher-id): BCP

Title: British Journal of Clinical Pharmacology

Publisher: John Wiley and Sons Inc. (Hoboken )

ISSN (Print): 0306-5251

ISSN (Electronic): 1365-2125

Publication date (Electronic): 08 May 2022

Publication date (Print): September 2022

Publication date PMC-release: 08 May 2022

Volume: 88

Issue: 9 ( doiID: 10.1111/bcp.v88.9 )

Pages: 4191-4198

Affiliations

[ ¹ ] The Royal Marsden NHS Foundation Trust London UK

[ ² ] South Tees Hospitals NHS Foundation Trust Middlesbrough UK

[ ³ ] The Mid Yorkshire Hospitals NHS Trust Wakefield UK

[ ⁴ ] Department of Practice and Policy UCL School of Pharmacy & University College London Hospitals NHS Foundation Trust London UK

Author notes

[*] [* ] Correspondence

Pinkie Chambers, Department of Practice and Policy, UCL School of Pharmacy & University College London Hospitals NHS Foundation Trust, 29–39 Brunswick Square, London WC1N 1AX, UK.

Email: p.chambers@ 123456ucl.ac.uk

Author information

Emma Foreman https://orcid.org/0000-0002-4348-9040

Calum Polwart https://orcid.org/0000-0002-4774-6366

Andrew Walker https://orcid.org/0000-0002-7836-4686

Pinkie Chambers https://orcid.org/0000-0002-6669-9411

Article

Publisher ID: BCP15363

DOI: 10.1111/bcp.15363

PMC ID: 9545865

PubMed ID: 35470452

SO-VID: e02e08ad-b0ca-4b18-b440-9e222875c7f2

License:

This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

History

Date revision received : 12 April 2022

Date received : 21 December 2021

Date accepted : 15 April 2022

Page count

Figures: 1, Tables: 3, Pages: 8, Words: 5049

Custom metadata

source-schema-version-number 2.0

cover-date September 2022

details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:6.2.0 mode:remove_FC converted:07.10.2022

ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine

Keywords: chemotherapy,h2 antagonists,hypersensitivity,paclitaxel

Data availability:

ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine

Keywords: chemotherapy, h2 antagonists, hypersensitivity, paclitaxel

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