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. 2021 Apr 4;11(4):269.
doi: 10.3390/jpm11040269.

What Is the Optimal Duration of Adjuvant Mitotane Therapy in Adrenocortical Carcinoma? An Unanswered Question

Vittoria Basile  1 , Soraya Puglisi  1 , Barbara Altieri  2 , Letizia Canu  3 , Rossella Libè  4 , Filippo Ceccato  5 , Felix Beuschlein  6   7 , Marcus Quinkler  8 , Anna Calabrese  1 , Paola Perotti  1 , Paola Berchialla  9 , Ulrich Dischinger  2 , Felix Megerle  2 , Eric Baudin  10 , Isabelle Bourdeau  11 , André Lacroix  11 , Paola Loli  12 , Alfredo Berruti  13 , Darko Kastelan  14 , Harm R Haak  15   16 , Martin Fassnacht  2   17 , Massimo Terzolo  1
Affiliations

What Is the Optimal Duration of Adjuvant Mitotane Therapy in Adrenocortical Carcinoma? An Unanswered Question

Vittoria Basile et al. J Pers Med. .

Abstract

A relevant issue on the treatment of adrenocortical carcinoma (ACC) concerns the optimal duration of adjuvant mitotane treatment. We tried to address this question, assessing whether a correlation exists between the duration of adjuvant mitotane treatment and recurrence-free survival (RFS) of patients with ACC. We conducted a multicenter retrospective analysis on 154 ACC patients treated for ≥12 months with adjuvant mitotane after radical surgery and who were free of disease at the mitotane stop. During a median follow-up of 38 months, 19 patients (12.3%) experienced recurrence. We calculated the RFS after mitotane (RFSAM), from the landmark time-point of mitotane discontinuation, to overcome immortal time bias. We found a wide variability in the duration of adjuvant mitotane treatment among different centers and also among patients cared for at the same center, reflecting heterogeneous practice. We did not find any survival advantage in patients treated for longer than 24 months. Moreover, the relationship between treatment duration and the frequency of ACC recurrence was not linear after stratifying our patients in tertiles of length of adjuvant treatment. In conclusion, the present findings do not support the concept that extending adjuvant mitotane treatment over two years is beneficial for ACC patients with low to moderate risk of recurrence.

Keywords: adjuvant treatment; adrenocortical cancer; mitotane; recurrence; recurrence free survival; timing.

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Conflict of interest statement

Puglisi Soraya has received a grant for scientific writing from HRA Pharma; Massimo Terzolo has received research grants from HRA Pharma, and advisory board honoraria from HRA Pharma and Corcept Therapeutics; the others authors have stated explicitly that there are no conflicts of interest in connection with this article. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Distribution of the duration of adjuvant mitotane for each center (only centers with at least five patients have been included in this analysis). 1 = Berlin; 2 = Munich; 3 = Wurzburg; 4 = Florence; 5 = Orbassano; 6 = Padua; 7 = IGR (Villejuif); 8 = Montreal. N = number of patients.
Figure 2
Figure 2
Kaplan–Meier estimates of recurrence-free survival (RFS) in patients treated <24 months versus patients treated >24 months.
Figure 3
Figure 3
Kaplan–Meier estimates of recurrence free survival after adjuvant mitotane discontinuation (RFSAM) in patients treated <24 months vs. patients treated >24 months.
See this image and copyright information in PMC

References

    1. Else T., Kim A.C., Sabolch A., Raymond V.M., Kandathil A., Caoili E.M., Jolly S., Miller B.S., Giordano T.J., Hammer G.D. Adrenocortical carcinoma. Endocr. Rev. 2014;35:282–326. doi: 10.1210/er.2013-1029. - DOI - PMC - PubMed
    1. Tierney J.F., Chivukula S.V., Poirier J., Pappas S.G., Schadde E., Hertl M., Kebebew E., Keutgen X. National Treatment Practice for Adrenocortical Carcinoma: Have They Changed and Have We Made Any Progress? J. Clin. Endocrinol. Metab. 2019;104:5948–5956. doi: 10.1210/jc.2019-00915. - DOI - PubMed
    1. Souteiro P., Donato S., Costa C., Pereira C.A., Simoes-Pereira J., Oliveira J., Belo S., Santos A.P., Cardoso H., Leite V., et al. Diagnosis, treatment, and survival analysis of adrenocortical carcinomas: A multicentric study. Hormones. 2020;19:197–203. doi: 10.1007/s42000-019-00161-1. - DOI - PubMed
    1. Amini N., Margonis G.A., Kim Y., Tran T.B., Postlewait L.M., Maithel S.K., Wang T.S., Evans D.B., Hatzaras I., Shenoy R., et al. Curative Resection of Adrenocortical Carcinoma: Rates and Patterns of Postoperative Recurrence. Ann. Surg. Oncol. 2016;23:126–133. doi: 10.1245/s10434-015-4810-y. - DOI - PMC - PubMed
    1. Bedrose S., Daher M., Altameemi L., Habra M.A. Adjuvant Therapy in Adrenocortical Carcinoma: Reflections and Future Directions. Cancers. 2020;12:508. doi: 10.3390/cancers12020508. - DOI - PMC - PubMed