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A prospective multi-centre, randomized study comparing the addition of tapering dexamethasone to other standard of care therapies for taxane-associated pain syndrome (TAPS) in breast cancer patients

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Abstract

Purpose

Taxane-associated pain syndrome (TAPS) is common with docetaxel and is characterised by myalgias and arthralgias starting 2–3 days after treatment and can last for up to 7 days. Anecdotal evidence suggests that corticosteroids can reduce TAPS. This multicentre, randomized trial evaluated the effect of additional tapering dexamethasone on TAPS.

Methods

130 breast cancer patients commencing docetaxel were randomized to dexamethasone premedication (8 mg/twice daily for 3 days) or dexamethasone premedication followed by tapering dexamethasone (4 mg/daily for 2 days followed by 2 mg/daily for 2 days). The primary endpoint was absolute change in FACT-Taxane questionnaire during the first chemotherapy cycle. Secondary endpoints: proportion of patients with clinically significant TAPS, QoL, pain and toxicity.

Results

110/130 patients had complete data included in the primary analysis. The fall in FACT-Taxane scores was lower in the experimental group on day 5 (p = 0.05), but not on day 7 (p = 0.21). There was no difference in FACT-Taxane scores over the entire study duration (p = 0.59). Fewer patients in the experimental arm reported TAPS on day 5 (30 vs. 47%). There was a borderline significant attenuation of impairment of QoL with experimental treatment on day 5 (p = 0.06), but not day 7 (p = 0.53). Tapered schedule was associated with more dyspepsia and insomnia.

Conclusion

A tapering schedule of dexamethasone was associated with a brief reduction in docetaxel-associated symptoms which was observed only during dexamethasone exposure and did not persist after discontinuation of the drug.

Trial Registration

ClinicalTrials.gov NCT03348696

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Data availability

De-identified dataset is available upon request and approval by the Ontario Cancer Research Ethics Board.

Code availability

Not applicable

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Acknowledgements

We are grateful to the patients, their families and their physicians for their participation in this study. Accrual by physician was: Clemons (84), Simos (23), Ng (6), Zibdawi (6), Hsu (3), Srikanthan (2), Gertler (2), Sehdev (1) Hilton (1) Rana (2).

Funding

Funding of this study was through the Rethinking Clinical Trials (REaCT program) and the Cancer Care Ontario - Clinical Programs and Quality Initiatives grant (Government of Ontario, 2017) to support the expansion of REaCT trials to other cancer centres in Ontario.

Author information

Authors and Affiliations

  1. Department of Medicine, Division of Medical Oncology, The Ottawa Hospital Cancer Centre, The Ottawa Hospital, 501 Smyth Road, Ottawa, ON, Canada

    Mark Clemons, Terry Ng, Bassam Basulaiman & Arif Awan

  2. Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada

    Mark Clemons, Marta Sienkiewicz, Dean Fergusson, Lisa Vandermeer, Deanna Saunders & Brian Hutton

  3. Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, ON, Canada

    Mark Clemons, Dean Fergusson & Brian Hutton

  4. The Stronach Regional Cancer Centre, Newmarket, ON, Canada

    Demetrios Simos & Labib Zibdawi

  5. Division of Medical Oncology & Hematology, Department of Medicine, Princess Margaret Cancer Centre and the University of Toronto, Toronto, ON, Canada

    Eitan Amir

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  1. Mark Clemons
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Consortia

on behalf of the REThinking Clinical Trials (REaCT) Investigators

Contributions

MC, DF, LV, BH, and EA designed the study and prepared the protocol. MC, DSimos, MS, TN, LZ, BB, AA, and DSaunders collected the data. MC acted as principal investigator, MS and DSaunders coordinated data entry and EA did the statistical analysis. MC, MS, LV, DSaunders and EA had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. MC, MS, DSaunders, and EA wrote the manuscript. All authors were involved in the critical review of the manuscript and approved the final version.

Corresponding author

Correspondence to Mark Clemons.

Ethics declarations

Ethics approval and consent to participate

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and the Ontario Cancer Research Ethics Board and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Integrated informed consent was obtained from all trial participants included in the study.

Consent for publication

The participants gave consent to de-identified publication of aggregate study results.

Conflict of interest

MC reports personal fees (honoraria) from Pfizer, outside the submitted work. TN reports personal fees (honoraria) from ARIAD, Takeda and Boehringer-Ingelheim, outside the submitted work. AA has participated on an advisory board for Novartis, Eli Lily, Exactis innovation and Pfizer, has received honoraria from Apobiologix and Roche and has received travel funds from Roche. BH reports consulting fees from Cornerstone Research, outside the submitted work. All other authors declare no competing interests.

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Clemons, M., Simos, D., Sienkiewicz, M. et al. A prospective multi-centre, randomized study comparing the addition of tapering dexamethasone to other standard of care therapies for taxane-associated pain syndrome (TAPS) in breast cancer patients. Support Care Cancer 29, 5787–5795 (2021). https://doi.org/10.1007/s00520-021-06142-8

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