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Cited by 167Adrenal and Paraganglionic TumorsAdrenal Hormones and DisordersHormonal Regulation and Hypertension

Prospective evaluation of mitotane toxicity in adrenocortical cancer patients treated adjuvantly

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Daffara, F., De Francia, S., Reimondo, G., Zaggia, B., Aroasio, E., Porpiglia, F., Volante, M., Termine, A. +5 more·2008·Endocrine Related Cancer
DOI 10.1677/erc-08-0103
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Abstract

Toxicity of adjuvant mitotane treatment is poorly known; thus, our aim was to assess prospectively the unwanted effects of adjuvant mitotane treatment and correlate the findings with mitotane concentrations. Seventeen consecutive patients who were treated with mitotane after radical resection of adrenocortical cancer (ACC) from 1999 to 2005 underwent physical examination, routine laboratory evaluation, monitoring of mitotane concentrations, and a hormonal work-up at baseline and every 3 months till ACC relapse or study end (December 2007). Mitotane toxicity was graded using NCI CTCAE criteria. All biochemical measurements were performed at our center and plasma mitotane was measured by an in-house HPLC assay. All the patients reached mitotane concentrations >14 mg/l and none of them discontinued definitively mitotane for toxicity; 14 patients maintained consistently elevated mitotane concentrations despite tapering of the drug. Side effects occurred in all patients but were manageable with palliative treatment and adjustment of hormone replacement therapy. Mitotane affected adrenal steroidogenesis with a more remarkable inhibition of cortisol and DHEAS than aldosterone. Mitotane induced either perturbation of thyroid function mimicking central hypothyroidism or, in male patients, inhibition of testosterone secretion. The discrepancy between salivary and serum cortisol, as well as between total and free testosterone, is due to the mitotane-induced increase in hormone-binding proteins which complicates interpretation of hormone measurements. A low-dose monitored regimen of mitotane is tolerable and able to maintain elevated drug concentrations in the long term. Mitotane exerts a complex effect on the endocrine system that may require multiple hormone replacement therapy.

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  • In 17 patients with radically resected adrenocortical carcinoma, mitotane was administered associated with glucocorticoid replacement therapy; excluding three patients under L-T4 treatment and one with subclinical hypothyroidism, during the first year, FT4 became subnormal in 12/13 evaluable patients (92%), with L-T4 replacement started after 9 months in four.

    “In 17 patients with radically resected ACC, mitotane was administered associated with glucocorticoid replacement therapy (90). Excluding three patients under L-T4 treatment and one with SCH, during the first year, FT4 became subnormal in 12/13 evaluable patients (92%), with L-T4 replacement started after 9 months in four.”

    From L-T4 therapy in the presence of pharmacological interferents (2020) · cites this paper as [90]

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  1. MacFarlane DA 1958 Cancer of the adrenal cortex: the natural history, prognosis and treatment in the study of 50 cases. Annals of the Royal College of Surgeons of England 109 613-618.

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Authors
Daffara, F., De Francia, S., Reimondo, G., Zaggia, B., Aroasio, E., Porpiglia, F., Volante, M., Termine, A., Di Carlo, F., Dogliotti, L., Angeli, A., Berruti, A., & Terzolo, M.
Affiliations
Ospedale San Luigi Gonzaga (IT)
Corresponding author
Terzolo, M.
ORCID
Venue
Endocrine Related Cancer
Publisher
Bioscientifica
Published
2008-09-10
Volume
15
Issue
4
Pages
1043-1053
ISSN
  • 1351-0088 (ISSN-L)
  • 1479-6821
DOI
10.1677/erc-08-0103
OpenAlex
W2166261257
Cited by
167
References
44
Citations by year
2026: 3 · 2025: 7 · 2024: 12 · 2023: 6 · 2022: 15 · 2021: 10 · 2020: 17 · 2019: 5 · 2018: 12 · 2017: 8 · 2016: 8 · 2015: 12 · 2014: 12 · 2013: 10 · 2012: 11
FWCI
6.67
Type
journal article
Language
en
Open access
Locations
  • Endocrine Related Cancer (publishedVersion)
  • PubMed (publishedVersion)
  • Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
  • Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
Funders
Regione Piemonte
Topics
  • Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
Keywords
mitotane, adrenocortical carcinoma, adjuvant therapy, drug toxicity, adrenal steroidogenesis, cortisol, dehydroepiandrosterone sulfate, aldosterone, thyroid function, central hypothyroidism, salivary cortisol, hormone binding proteins, hormone replacement therapy
MeSH terms
Adrenal Cortex Neoplasms, Adult, Chromatography, High Pressure Liquid, Female, Humans, Hydrocortisone, Hypothyroidism, Male, Middle Aged, Mitotane, Neoplasm Staging, Prospective Studies, Testosterone, Survival Rate, Chemotherapy, Adjuvant, Antineoplastic Agents, Hormonal, Young Adult

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