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Pilot study of treatment of patients with deep infiltrative endometriosis with methotrexate carried in lipid nanoparticles

  • Gynecologic Endocrinology and Reproductive Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Objective

Previously, lipid nanoparticles (LDE) injected in women with endometriosis were shown to concentrate in the lesions. Here, the safety and feasibility of LDE carrying methotrexate (MTX) to treat deep infiltrating endometriosis was tested.

Design

Prospective pilot study.

Setting

Perola Byington Hospital Reference for Women’s Health.

Subjects

Eleven volunteers (aged 30–47 years, BMI 26.15 ± 6.50 kg/m2) with endometriosis with visual analog scale pelvic pain scores (VAS) > 7 and rectosigmoid lesions were enrolled in the study.

Intervention

Three patients were treated with LDE–MTX at single intravenous 25 mg/m2 dose of MTX and eight patients with two 25 mg/m2 doses with 1-week interval.

Main outcome measures

Clinical complaints, blood count, and biochemistry were analyzed before treatment and on days 90, 120, and 180 after LDE–MTX administration. Endometriotic lesions were evaluated by pelvic and transvaginal ultrasound (TVUS) before treatment and on days 30 and 180 after LDE–MTX administration.

Results

No clinical complaints related with LDE–MTX treatment were reported by the patients, and no hematologic, renal, or hepatic toxicities were observed in the laboratorial exams. FSH, LH, TSH, free T4, anti-Müllerian hormone, and prolactin levels were also within normal ranges during the observation period. Scores for deep dyspareunia (p < 0.001), chronic pelvic pain (p = 0.008), and dyschezia (p = 0.025) were improved over the 180-day observation period. There was a non-significant trend for reduction of VAS scores for dysmenorrhea. Bowel lesions by TVUS were unchanged. No clear differences between the two dose levels in therapeutic responses were observed.

Conclusion

Results support the safety and feasibility of using LDE–MTX in women with deep infiltrating endometriosis as a novel and promising therapy for the disease. More prolonged treatment schemes should be tested in future placebo-controlled studies aiming to establish the usefulness of this novel nanomedicine approach.

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Acknowledgements

We would like to thank Helymar da Costa Machado, statistician from Hospital da Mulher (CAISM), University of Campinas, for assistance with the statistical analysis. We would also like to thank Kelly Mancini, a supervising nurse of the chemotherapy sector at the Perola Byington Hospital, for providing all the logistic organizations to receive our patients.

Funding

This study was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, grant 2014/03742-0), Brazil.

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Authors and Affiliations

  1. Gynecological Endoscopy Center of the Perola Byington Hospital Reference for Women’s Health, São Paulo, Brazil

    Roberta Avila-Tavares & Luciano Gibran

  2. Department of Obstetrics and Gynecology, School of Medical Sciences, University of Campinas, Campinas, Brazil

    Roberta Avila-Tavares & Luiz Gustavo Oliveira Brito

  3. Lipid Metabolism Laboratory, Heart Institute, University of Sao Paulo, São Paulo, Brazil

    Thauany Martins Tavoni & Raul Cavalcante Maranhão

  4. Alta Medicina Diagnóstica, São Paulo, Brazil

    Manoel Orlando Gonçalves

  5. Department of Obstetrics and Gynecology, Medical School Hospital, University of Sao Paulo, São Paulo, Brazil

    Edmund Chada Baracat & Sergio Podgaec

Authors
  1. Roberta Avila-Tavares
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  2. Luciano Gibran
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  3. Luiz Gustavo Oliveira Brito
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  4. Thauany Martins Tavoni
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  5. Manoel Orlando Gonçalves
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  6. Edmund Chada Baracat
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  7. Raul Cavalcante Maranhão
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  8. Sergio Podgaec
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Corresponding author

Correspondence to Roberta Avila-Tavares.

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Conflict of interest

R.A-T. has nothing to disclose. L.G. has nothing to disclose.L.G.O.B. has nothing to disclose. T.M.T. has nothing to disclose. M.O.G. has nothing to disclose. E.C.B. has nothing to disclose.R.C.M. has nothing to disclose. S.P. has nothing to disclose.

Data sharing statement

All data generated in the current study are available from the corresponding author upon request.

IRB ethical approval statement

The study protocol was approved by the Institutional Review Board of the Perola Byington Hospital (#1.937.704) and by the Ethical Committee of the Hospital of the School of Medicine of the University of Sao Paulo (#3.402.300).

Trial registration:

RBR-7jx2byj, URL: https://ensaiosclinicos.gov.br/rg/RBR-7jx2byj Date of registration: 01/11/22.

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Avila-Tavares, R., Gibran, L., Brito, L.G.O. et al. Pilot study of treatment of patients with deep infiltrative endometriosis with methotrexate carried in lipid nanoparticles. Arch Gynecol Obstet 309, 659–667 (2024). https://doi.org/10.1007/s00404-023-07246-8

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