prikaz prve stranice dokumenta Adjuvant mitotane versus surveillance in low-grade, localised adrenocortical carcinoma (ADIUVO): an international, multicentre, open-label, randomised, phase 3 trial and observational study
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Scientific paper - Original scientific paper
Adjuvant mitotane versus surveillance in low-grade, localised adrenocortical carcinoma (ADIUVO): an international, multicentre, open-label, randomised, phase 3 trial and observational study
The Lancet Diabetes & Endocrinology, 11 (2023), 10; 720-730. https://doi.org/10.1016/S2213-8587(23)00193-6
Terzolo, Massimo; Fassnacht, Martin; Perotti, Paola; Libe, Rossella; Kaštelan, Darko; Lacroix, Andre; Arlt, Wiebke; Haak, Haram Reinout; Loli, paola; Decoudier, Benedicte; Lasolle, Helene; Quinkler, Marcus; Haissaguerre, Magalie; Chabre, Olivier; Caron, Philippe; Stigliano, Antonio; Giordano, Roberta; Zatelli, Maria Chiara; Bancos, Irina; Fragoso, Maria Candida Barisson Villares; Canu, Letizia; Luconi, Michaela; Puglisi, Soraya; Basiel, Vittoria; Reimondo, Giuseppe; Kroiss, Matthias; Megerle, Felix; Hahner, Stefanie; Kimpel, Otilia; Dušek, Tina; Nölting, Svenja; Bourdeau, Isabelle; Baudin, Eric; Berchialla, Paola; Bovis, Francesca; Sormani, Maria Pia; Bruzzi, Paolo; Beuschlein, Felix; Bertherat, Jerome; Berruti, Alfredo More authors...

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Terzolo, M., Fassnacht, M., Perotti, P., Libe, R., Kaštelan, D., Lacroix, A. ... Berruti, A. (2023). Adjuvant mitotane versus surveillance in low-grade, localised adrenocortical carcinoma (ADIUVO): an international, multicentre, open-label, randomised, phase 3 trial and observational study. The Lancet Diabetes & Endocrinology, 11. (10), 720-730. doi: 10.1016/S2213-8587(23)00193-6

Terzolo, Massimo, et al. "Adjuvant mitotane versus surveillance in low-grade, localised adrenocortical carcinoma (ADIUVO): an international, multicentre, open-label, randomised, phase 3 trial and observational study." The Lancet Diabetes & Endocrinology, vol. 11, no. 10, 2023, pp. 720-730. https://doi.org/10.1016/S2213-8587(23)00193-6

Terzolo, Massimo, Martin Fassnacht, Paola Perotti, Rossella Libe, Darko Kaštelan, Andre Lacroix, Wiebke Arlt, et al. "Adjuvant mitotane versus surveillance in low-grade, localised adrenocortical carcinoma (ADIUVO): an international, multicentre, open-label, randomised, phase 3 trial and observational study." The Lancet Diabetes & Endocrinology 11, no. 10 (2023): 720-730. https://doi.org/10.1016/S2213-8587(23)00193-6

Terzolo, M., et al. (2023) 'Adjuvant mitotane versus surveillance in low-grade, localised adrenocortical carcinoma (ADIUVO): an international, multicentre, open-label, randomised, phase 3 trial and observational study', The Lancet Diabetes & Endocrinology, 11(10), pp. 720-730. doi: 10.1016/S2213-8587(23)00193-6

Terzolo M, Fassnacht M, Perotti P, Libe R, Kaštelan D, Lacroix A, and sur.. Adjuvant mitotane versus surveillance in low-grade, localised adrenocortical carcinoma (ADIUVO): an international, multicentre, open-label, randomised, phase 3 trial and observational study. The Lancet Diabetes & Endocrinology [Internet]. 2023 October [cited 2024 November 14];11(10):720-730. doi: 10.1016/S2213-8587(23)00193-6

M. Terzolo, et al., "Adjuvant mitotane versus surveillance in low-grade, localised adrenocortical carcinoma (ADIUVO): an international, multicentre, open-label, randomised, phase 3 trial and observational study", The Lancet Diabetes & Endocrinology, vol. 11, no. 10, pp. 720-730, October 2023. [Online]. Available at: https://urn.nsk.hr/urn:nbn:hr:105:260017. [Accessed: 14 November 2024]

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Title (english)Adjuvant mitotane versus surveillance in low-grade, localised adrenocortical carcinoma (ADIUVO): an international, multicentre, open-label, randomised, phase 3 trial and observational study
AuthorMassimo Terzolo
AuthorMartin Fassnacht
AuthorPaola Perotti
AuthorRossella Libe
AuthorDarko Kaštelan
AuthorAndre Lacroix
AuthorWiebke Arlt
AuthorHaram Reinout Haak
Authorpaola Loli
AuthorBenedicte Decoudier
AuthorHelene Lasolle
AuthorMarcus Quinkler
AuthorMagalie Haissaguerre
AuthorOlivier Chabre
AuthorPhilippe Caron
AuthorAntonio Stigliano
AuthorRoberta Giordano
AuthorMaria Chiara Zatelli
AuthorIrina Bancos
AuthorMaria Candida Barisson Villares Fragoso
AuthorLetizia Canu
AuthorMichaela Luconi
AuthorSoraya Puglisi
AuthorVittoria Basiel
AuthorGiuseppe Reimondo
AuthorMatthias Kroiss
AuthorFelix Megerle
AuthorStefanie Hahner
AuthorOtilia Kimpel
AuthorTina Dušek
AuthorSvenja Nölting
AuthorIsabelle Bourdeau
AuthorEric Baudin
AuthorPaola Berchialla
AuthorFrancesca Bovis
AuthorMaria Pia Sormani
AuthorPaolo Bruzzi
AuthorFelix Beuschlein
AuthorJerome Bertherat
AuthorAlfredo Berruti
Author's institutionUniversity of Zagreb
School of Medicine
(Department of Internal Medicine)
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Clinical Medical Sciences
Internal Medicine
Abstract (english)
Background: Adjuvant treatment with mitotane is commonly used after resection of adrenocortical carcinoma; however, treatment remains controversial, particularly if risk of recurrence is not high. We aimed to assess the efficacy and safety of adjuvant mitotane compared with surveillance alone following complete tumour resection in patients with adrenocortical carcinoma considered to be at low to intermediate risk of recurrence. Methods: ADIUVO was a multicentre, open-label, parallel, randomised, phase 3 trial done in 23 centres across seven countries. Patients aged 18 years or older with adrenocortical carcinoma and low to intermediate risk of recurrence (R0, stage I-III, and Ki67 ≤10%) were randomly assigned to adjuvant oral mitotane two or three times daily (the dose was adjusted by the local investigator with the target of reaching and maintaining plasma mitotane concentrations of 14-20 mg/L) for 2 years or surveillance alone. All consecutive patients at 14 study centres fulfilling the eligibility criteria of the ADIUVO trial who refused randomisation and agreed on data collection via the European Network for the Study of Adrenal Tumors adrenocortical carcinoma registry were included prospectively in the ADIUVO Observational study. The primary endpoint was recurrence-free survival, defined as the time from randomisation to the first radiological evidence of recurrence or death from any cause (whichever occurred first), assessed in all randomly assigned patients by intention to treat. Overall survival, defined as time from the date of randomisation to the date of death from any cause, was a secondary endpoint analysed by intention to treat in all randomly assigned patients. Safety was assessed in all patients who adhered to the assigned regimen, which was defined by taking at least one tablet of mitotane in the mitotane group and no mitotane at all in the surveillance group. The ADIUVO trial is registered with ClinicalTrials.gov, NCT00777244, and is now complete. Findings: Between Oct 23, 2008, and Dec 27, 2018, 45 patients were randomly assigned to mitotane and 46 to surveillance alone. Because the study was discontinued prematurely, 5-year recurrence-free and overall survival are reported instead of recurrence-free and overall survival as defined in the protocol. 5-year recurrence-free survival was 79% (95% CI 67-94) in the mitotane group and 75% (63-90) in the surveillance group (hazard ratio 0·74 [95% CI 0·30-1·85]). Two people in the mitotane group and five people in the surveillance group died, and 5-year overall survival was not significantly different (95% [95% CI 89-100] in the mitotane group and 86% [74-100] in the surveillance group). All 42 patients who received mitotane had adverse events, and eight (19%) discontinued treatment. There were no grade 4 adverse events or treatment-related deaths. Interpretation: Adjuvant mitotane might not be indicated in patients with low-grade, localised adrenocortical carcinoma considering the relatively good prognosis of these patients, and no significant improvement in recurrence-free survival and treatment-associated toxicity in the mitotane group. However, the study was discontinued prematurely due to slow recruitment and cannot rule out an efficacy of treatment.
Keywords (english)
Languageenglish
Publication typeScientific paper - Original scientific paper
Publication statusPublished
Peer reviewPeer review
Publication versionPublished version
Journal titleThe Lancet Diabetes & Endocrinology
Numberingvol. 11, no. 10, pp. 720-730
p-ISSN2213-8587
e-ISSN2213-8595
DOIhttps://doi.org/10.1016/S2213-8587(23)00193-6
URN:NBNurn:nbn:hr:105:260017
Publication2023-10
Document URLhttps://linkinghub.elsevier.com/retrieve/pii/S2213-8587(23)00193-6
Type of resourceText
Access conditionsOpen access
Terms of useLicence Attribution 4.0 International (CC BY 4.0) icon
Created on2024-08-21 07:53:51