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A phase 2 study for evaluating doxycycline 50 mg once daily and 100 mg once daily as preemptive treatment for skin toxicity in patients with metastatic colorectal cancer treated with an anti-EGFR and chemotherapy

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Abstract

Purpose

To assess the efficacy, safety, and quality-of-life outcomes of doxycycline 50 or 100 mg once daily in the prevention of skin toxicity in patients undergoing chemotherapy plus anti-EGFR therapy as first-line treatment of metastatic colorectal cancer (mCRC).

Methods

Phase II, multicenter, single-arm, exploratory study was conducted in 7 Spanish hospitals. The primary study outcome was the incidence of ≥ grade 2 skin toxicities during the 6-week skin treatment period. Quality of life was assessed with the Dermatology Life Quality Index (DLQI) questionnaire. Patients had to receive either doxycycline 50 mg once daily in a first stage with 10 patients, or, if more than three patients presented ≥ grade 2 skin toxicities, the next 30 patients had to receive 100 mg once daily.

Results

Thirty-four patients with RAS wild-type mCRC were enrolled in the study. Ten patients were first treated with doxycycline 50 mg once daily, and the following 24 were treated with doxycycline 100 mg once daily. A total of 60.0% (95% CI 29.6–90.0) and 20.8% (95% CI 4.6–37.0) of patients who received doxycycline 50 mg/day and 100 mg/day, respectively, had at least one ≥ grade 2 skin toxicity. Patients treated with doxycycline 100 mg once daily experienced less QoL deterioration. Only 1 patient reported a mild doxycycline-related gastrointestinal adverse event.

Conclusion

Our results suggest that doxycycline doses as low as 100 mg once daily are efficacious and well tolerated for the prevention of skin toxicity in patients with mCRC who undergo treatment with chemotherapy plus EGFR-targeted therapies.

Trial registration

ClinicalTrials.gov NCT03448731.

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Data availability

The clinical trial data are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors thank the CRIS Foundation for sponsoring the study. The authors also thank Juan Luis Sanz and Susana Vara (APICES, Madrid; Spain) for their support with the study design, setup, coordination and project management, monitoring, and statistical analysis and Fernando Rico-Villademoros (APICES, Madrid, Spain) for writing a draft of this manuscript.

Funding

The study was funded by Amgen S.A. Amgen S.A. reviewed a draft of this manuscript and provided non-binding comments to the authors.

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Authors and Affiliations

Authors

Contributions

Patricia Ramírez-Daffós: conceptualization, methodology, formal analysis, investigation, writing-original draft, and writing-review and editing.

Encarnación Jiménez-Orozco, Matilde Bolaños, Beatriz González Astorga, Sandra Rubiales, Eduardo Ceballos-Barbancho, José Manuel Rodríguez García, and Juan-José Reina: investigation and writing-review and editing.

Corresponding author

Correspondence to Patricia Ramírez-Daffós.

Ethics declarations

Ethics approval

This study was approved by the independent ethics committee CEIm Provincial de Sevilla (Sevilla, Spain).

Consent to participate

Written informed consent was obtained from all individual participants included in the study.

Consent for publication

Not applicable.

Competing interests

Beatriz González Astorga has received Speaker honorarium from Merck, Amgen, Sanofi, and Servier; Eduardo Ceballos-Barbancho has received research grants to institution from Angem; Juan José Reina has been advisory board member for Roche, Merck, Amgen, Servier, Bayer, Sanofi, Pfizer, Astra-Zeneca, and Ipsen. The remaining authors declare no conflict of interest.

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Ramírez-Daffós, P., Jiménez-Orozco, E., Bolaños, M. et al. A phase 2 study for evaluating doxycycline 50 mg once daily and 100 mg once daily as preemptive treatment for skin toxicity in patients with metastatic colorectal cancer treated with an anti-EGFR and chemotherapy. Support Care Cancer 30, 8081–8088 (2022). https://doi.org/10.1007/s00520-022-07254-5

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