How close are we to personalized mitotane dosing in the treatment of adrenocortical carcinoma? State of the art and future perspectives

References

• Kerkhofs TM, Verhoeven RH, Van Der Zwan JM, et al. Adrenocortical carcinoma: a population-based study on incidence and survival in the netherlands since 1993. Eur.J.Cancer. 2013;49(11):2579–2586.
   PubMed Web of Science ®Google Scholar
• Fassnacht M, Dekkers O, Else T, et al. European society of endocrinology clinical practice guidelines on the management of adrenocortical carcinoma in adults, in collaboration with the european network for the study of adrenal tumors. Eur.J.Endocrinol. 2018;179(4):G1-G46.
   Web of Science ®Google Scholar
• Fassnacht M, Assie G, Baudin E, et al. Electronic address: clinicalguidelines@esmo org, adrenocortical carcinomas and malignant phaeochromocytomas: ESMO-EURACAN clinical practice guidelines for diagnosis, treatment and follow-up. Ann.Oncol. 2020;31(11):1476–1490.
   PubMed Web of Science ®Google Scholar
• Altieri B, Ronchi CL, Kroiss M, et al. Next-generation therapies for adrenocortical carcinoma. Best Pract Res Clin Endocrinol Metab. 2020;34(3):101434.
   PubMed Web of Science ®Google Scholar
• Nelson AA, Woodard G. Adrenal cortical atrophy and liver damage produced in dogs by feeding 2,2-bis-(parachloro-phenyl)-1,1-dichloroethane. Fed.Proc. 1948;7:277.
   PubMedGoogle Scholar
• Bergenstal DM, Hertz R, Lipsett MB, et al. Chemotherapy of adrenocortical cancer with O,P’DDD. Ann Intern Med. 1960;53:672–682.
   Web of Science ®Google Scholar
• Basile V, Puglisi S, Calabrese A, et al. Unwanted hormonal and metabolic effects of postoperative adjuvant mitotane treatment for adrenocortical cancer. Cancers (Basel). 2020;12(9):2615.
   Web of Science ®Google Scholar
• Kroiss M, Quinkler M, Lutz WK, et al. Drug interactions with mitotane by induction of CYP3A4 metabolism in the clinical management of adrenocortical carcinoma. Clin Endocrinol (Oxf). 2011;75(5):585–591.
   PubMed Web of Science ®Google Scholar
• Chortis V, Taylor AE, Schneider P, et al. Mitotane therapy in adrenocortical cancer induces CYP3A4 and Inhibits 5alpha-reductase, explaining the need for personalized glucocorticoid and androgen replacement. J.Clin.Endocrinol.Metab. 2013;98(1):161–171.
   PubMed Web of Science ®Google Scholar
• Moolenaar AJ, Niewint JW, Oei IT. Estimation of O,P’-DDD in plasma by gas-liquid chromatography. Clin.Chim.Acta. 1977;76(2):213–218.
   PubMed Web of Science ®Google Scholar
• Hermsen IG, Den Hartigh J, Haak HR. Mitotane serum level analysis; good agreement between two different assays. Clin Endocrinol (Oxf). 2010;73(2):271–272.
   PubMed Web of Science ®Google Scholar
• Friedl B, Kurlbaum M, Kroiss M, et al. A method for the minimally invasive drug monitoring of mitotane by means of volumetric absorptive microsampling for a home-based therapeutic drug monitoring. Anal Bioanal Chem. 2019;411(17):3951–3962.
   PubMed Web of Science ®Google Scholar
• Von Slooten H, Van Seters AP, Smeenk D, et al. O,P’-DDD (mitotane) levels in plasma and tissues during chemotherapy and at autopsy. Cancer Chemother Pharmacol. 1982;9(2):85–88.
   PubMed Web of Science ®Google Scholar
• Van Slooten H, Moolenaar AJ, Van Seters AP, et al. The treatment of adrenocortical carcinoma with O,P’-DDD: prognostic implications of serum level monitoring. Eur J Cancer Clin Oncol. 1984;20(1):47–53.
   PubMedGoogle Scholar
• Haak HR, Hermans J, Van De Velde CJ, et al. Optimal treatment of adrenocortical carcinoma with mitotane: results in a consecutive series of 96 patients. Br.J.Cancer. 1994;69(5):947–951.
   PubMed Web of Science ®Google Scholar
• Baudin E, Pellegriti G, Bonnay M, et al. Impact of monitoring plasma 1,1-dichlorodiphenildichloroethane (O,P’DDD) levels on the treatment of patients with adrenocortical carcinoma. Cancer. 2001;92(6):1385–1392.
   PubMed Web of Science ®Google Scholar
• Hermsen IG, Fassnacht M, Terzolo M, et al. Plasma concentrations of O,P’DDD, O,P’DDA, and O,P’DDE as predictors of tumor response to mitotane in adrenocortical carcinoma: results of a retrospective ENS@T multicenter study. J.Clin.Endocrinol.Metab. 2011;96(6):1844–1851.
   PubMed Web of Science ®Google Scholar
• Terzolo M, Baudin AE, Ardito A, et al. Mitotane levels predict the outcome of patients with adrenocortical carcinoma treated adjuvantly following radical resection. Eur.J.Endocrinol. 2013;169(3):263–270.
   PubMed Web of Science ®Google Scholar
• Puglisi S, Calabrese A, Basile V, et al. Mitotane concentrations influence the risk of recurrence in adrenocortical carcinoma patients on adjuvant treatment. J.Clin.Med 2019;8(11):1850.
   PubMed Web of Science ®Google Scholar
• Puglisi S, Calabrese A, Basile V, et al. Mitotane concentrations influence outcome in patients with advanced adrenocortical carcinoma. Cancers (Basel). 2020;12(3):740.
   Web of Science ®Google Scholar
• Kerkhofs TM, Derijks LJ, Ettaieb MH, et al. Short-term variation in plasma mitotane levels confirms the importance of trough level monitoring. Eur.J.Endocrinol. 2014;171(6):677–683.
   PubMed Web of Science ®Google Scholar
• Cusato J, De Francia S, Allegra S, et al. Circannual variation of mitotane and its metabolites plasma levels in patients with adrenocortical carcinoma. J.Pharm.Pharmacol. 2017;69(11):1524–1530.
   PubMed Web of Science ®Google Scholar
• Kerkhofs TM, Baudin E, Terzolo M, et al. Comparison of two mitotane starting dose regimens in patients with advanced adrenocortical carcinoma. J.Clin.Endocrinol.Metab. 2013;98(12):4759–4767.
   PubMed Web of Science ®Google Scholar
• Mauclere-Denost S, Leboulleux S, Borget I, et al. High-dose mitotane strategy in adrenocortical carcinoma: prospective analysis of plasma mitotane measurement during the first 3 months of follow-up. Eur.J.Endocrinol. 2012;166(2):261–268.
   PubMed Web of Science ®Google Scholar
• Faggiano A, Leboulleux S, Young J, et al. Rapidly progressing high O,P’DDD doses shorten the time required to reach the therapeutic threshold with an acceptable tolerance: preliminary results. Clin Endocrinol (Oxf). 2006;64(1):110–113.
   PubMed Web of Science ®Google Scholar
• Terzolo M, Pia A, Berruti A, et al. Low-dose monitored mitotane treatment achieves the therapeutic range with manageable side effects in patients with adrenocortical cancer. J.Clin.Endocrinol.Metab. 2000;85(6):2234–2238.
   PubMed Web of Science ®Google Scholar
• Moy RH. Studies of the pharmacology of O,p’DDD in man. J Lab Clin Med. 1961;58:296–304.
   PubMed Web of Science ®Google Scholar
• Moolenaar AJ, Van Slooten H, Van Seters AP, et al. Blood levels of O,P’-DDD following administration in various vehicles after a single dose and during long-term treatment. Cancer Chemother Pharmacol. 1981;7(1):51–54.
   PubMed Web of Science ®Google Scholar
• Corso CR, Acco A, Bach C, et al. Pharmacological profile and effects of mitotane in adrenocortical carcinoma. Br.J.Clin.Pharmacol. 2020. DOI:10.1111/bcp.14721.
   PubMed Web of Science ®Google Scholar
• Kerkhofs TM, Derijks LJ, Ettaieb H, et al. Development of a pharmacokinetic model of mitotane: toward personalized dosing in adrenocortical carcinoma. Ther Drug Monit. 2015;37(1):58–65.
   PubMed Web of Science ®Google Scholar
• Arshad U, Taubert M, Kurlbaum M, et al. Enzyme autoinduction by mitotane supported by population pharmacokinetic modelling in a large cohort of adrenocortical carcinoma patients. Eur.J.Endocrinol. 2018;179(5):287–297.
   PubMed Web of Science ®Google Scholar
• Cazaubon Y, Talineau Y, Feliu C, et al. Population pharmacokinetics modelling and simulation of mitotane in patients with adrenocortical carcinoma: an individualized dose regimen to target all patients at three months? Pharmaceutics. 2019;11(11):566.
   PubMed Web of Science ®Google Scholar
• Yin A, Ettaieb MHT, Swen JJ, et al. Population pharmacokinetic and pharmacogenetic analysis of mitotane in patients with adrenocortical carcinoma: towards individualized dosing. Clin.Pharmacokinet. 2021;60(1):89-102.
   Web of Science ®Google Scholar
• Cai W, Counsell RE, Djanegara T, et al. Metabolic activation and binding of mitotane in adrenal cortex homogenates. J.Pharm.Sci. 1995;84:134–138.
   PubMed Web of Science ®Google Scholar
• Scripture CD, Sparreboom A, Figg WD. Modulation of cytochrome P450 activity: implications for cancer therapy. Lancet Oncol. 2005;6(10):780–789.
   PubMed Web of Science ®Google Scholar
• Mornar A, Sertic M, Turk N, et al. Simultaneous analysis of mitotane and its main metabolites in human blood and urine samples by SPE-HPLC technique. Biomed.Chromatogr. 2012;26(11):1308–1314.
   PubMed Web of Science ®Google Scholar
• D’Avolio A, De Francia S, Basile V, et al. Influence of the CYP2B6 polymorphism on the pharmacokinetics of mitotane. Pharmacogenet Genomics. 2013;23(6):293–300.
   PubMed Web of Science ®Google Scholar
• Ronchi CL, Sbiera S, Volante M, et al. CYP2W1 is highly expressed in adrenal glands and is positively associated with the response to mitotane in adrenocortical carcinoma. PLoS One. 2014;9(8):e105855.
   PubMed Web of Science ®Google Scholar
• Altieri B, Sbiera S, Herterich S, et al. Effects of germline CYP2W1*6 and CYP2B6*6 single nucleotide polymorphisms on mitotane treatment in adrenocortical carcinoma: a multicenter ENSAT study. Cancers (Basel). 2020;12(2):359.
   Web of Science ®Google Scholar
• Attivi D, Ajana I, Astier A, et al. Development of microemulsion of mitotane for improvement of oral bioavailability. Drug Dev Ind Pharm. 2010;36(4):421–427.
   PubMed Web of Science ®Google Scholar
• Menaa F, Menaa B. Development of mitotane lipid nanocarriers and enantiomers: two-in-one solution to efficiently treat adreno-cortical carcinoma. Curr.Med.Chem. 2012;19(34):5854–5862.
   PubMed Web of Science ®Google Scholar
• Zancanella P, Oliveira DML, De Oliveira BH, et al. Mitotane liposomes for potential treatment of adrenal cortical carcinoma: ex vivo intestinal permeation and in vivo bioavailability. Pharm.Dev.Technol. 2020;25(8):949–961.
   PubMed Web of Science ®Google Scholar
• Haider MS, Schreiner J, Kendl S, et al. A micellar mitotane formulation with high drug-loading and solubility: physico-chemical characterization and cytotoxicity studies in 2D and 3D in vitro tumor models. Macromol.Biosci. 2020;20(1):e1900178.
   PubMed Web of Science ®Google Scholar
• Fassnacht M, Terzolo M, Allolio B, et al. Combination chemotherapy in advanced adrenocortical carcinoma. N.Engl.J.Med. 2012;366(23):2189–2197.
   PubMed Web of Science ®Google Scholar
• Villa R, Orlandi L, Berruti A, et al. Modulation of cytotoxic drug activity by mitotane and lonidamine in human adrenocortical carcinoma cells. Int.J.Oncol. 1999;14(1):133–138.
   PubMed Web of Science ®Google Scholar
• Gagliano T, Gentilin E, Benfini K, et al. Mitotane enhances doxorubicin cytotoxic activity by inhibiting P-gp in human adrenocortical carcinoma cells. Endocrine. 2014;47(3):943–951.
   PubMed Web of Science ®Google Scholar
• Jouinot A, Royer B, Chatelut E, et al. Pharmacokinetic interaction between mitotane and etoposide in adrenal carcinoma: a pilot study. Endocr Connect. 2018;7(12):1409–1414.
   PubMed Web of Science ®Google Scholar
• Germano A, Rapa I, Volante M, et al. Cytotoxic activity of gemcitabine, alone or in combination with mitotane, in adrenocortical carcinoma cell lines. Mol.Cell.Endocrinol. 2014;382(1):1–7.
   PubMed Web of Science ®Google Scholar
• Germano A, Rapa I, Volante M, et al. RRM1 modulates mitotane activity in adrenal cancer cells interfering with its metabolization. Mol.Cell.Endocrinol. 2015;401:105–110.
   PubMed Web of Science ®Google Scholar
• Creemers SG, Van Koetsveld PM, Van Den Dungen ES, et al. Inhibition of human adrenocortical cancer cell growth by temozolomide in vitro and the role of the MGMT gene. J.Clin.Endocrinol.Metab. 2016;101(12):4574–4584.
   PubMed Web of Science ®Google Scholar
• Borges KS, Andrade AF, Silveira VS, et al. The aurora kinase inhibitor AMG 900 increases apoptosis and induces chemosensitivity to anticancer drugs in the NCI-H295 adrenocortical carcinoma cell line. Anticancer Drugs. 2017;28(6):634–644.
   PubMed Web of Science ®Google Scholar
• Fragni M, Fiorentini C, Rossini E, et al. In vitro antitumor activity of progesterone in human adrenocortical carcinoma. Endocrine. 2019;63(3):592–601.
   PubMed Web of Science ®Google Scholar
• Fragni M, Palma Lopez LP, Rossini E, et al. In vitro cytotoxicity of cabazitaxel in adrenocortical carcinoma cell lines and human adrenocortical carcinoma primary cell cultures. Mol.Cell.Endocrinol. 2019;498:110585.
   PubMed Web of Science ®Google Scholar
• Abate A, Rossini E, Bonini SA, et al. Cytotoxic effect of trabectedin in human adrenocortical carcinoma cell lines and primary cells. Cancers (Basel). 2020;12(4):928.
   Web of Science ®Google Scholar
• Nagy Z, Baghy K, Hunyadi-Gulyas E, et al. Evaluation of 9-Cis retinoic acid and mitotane as antitumoral agents in an adrenocortical xenograft model. Am.J.Cancer.Res. 2015;5(12):3645–3658.
   PubMed Web of Science ®Google Scholar
• Bertazza L, Barollo S, Mari ME, et al. Biological effects of EF24, a curcumin derivative, alone or combined with mitotane in adrenocortical tumor cell lines. Molecules. 2019;24(12):2202.
   PubMed Web of Science ®Google Scholar
• Rubin B, Pilon C, Pezzani R, et al. The effects of mitotane and 1alpha,25-dihydroxyvitamin D3 on wnt/beta-catenin signaling in human adrenocortical carcinoma cells. J.Endocrinol.Invest. 2020;43(3):357–367.
   PubMed Web of Science ®Google Scholar
• Head L, Kiseljak-Vassiliades K, Clark TJ, et al. Response to immunotherapy in combination with mitotane in patients with metastatic adrenocortical cancer. J Endocr Soc. 2019;3(12):2295–2304.
   PubMed Web of Science ®Google Scholar
• Germano A, Rapa I, Duregon E, et al. Tissue expression and pharmacological in vitro analyses of mTOR and SSTR pathways in adrenocortical carcinoma. Endocr Pathol. 2017;28(2):95–102.
   PubMed Web of Science ®Google Scholar
• Shawa H, Deniz F, Bazerbashi H, et al. Mitotane-induced hyperlipidemia: a retrospective cohort study. Int.J.Endocrinol. 2013;2013:624962.
   PubMed Web of Science ®Google Scholar
• Kroiss M, Plonne D, Kendl S, et al. Association of mitotane with chylomicrons and serum lipoproteins: practical implications for treatment of adrenocortical carcinoma. Eur.J.Endocrinol. 2016;174(3):343–353.
   PubMed Web of Science ®Google Scholar
• Hescot S, Seck A, Guerin M, et al. Lipoprotein-free mitotane exerts high cytotoxic activity in adrenocortical carcinoma. J.Clin.Endocrinol.Metab. 2015;100(8):2890–2898.
   PubMed Web of Science ®Google Scholar
• Sbiera S, Leich E, Liebisch G, et al. Mitotane inhibits sterol-O-acyl transferase 1 triggering lipid-mediated endoplasmic reticulum stress and apoptosis in adrenocortical carcinoma cells. Endocrinology. 2015;156(11):3895–3908.
   PubMed Web of Science ®Google Scholar
• Weigand I, Altieri B, Lacombe AMF, et al. Expression of SOAT1 in adrenocortical carcinoma and response to mitotane monotherapy: An ENSAT multicenter study. J.Clin.Endocrinol.Metab. 2020;105(8):2642–2653.
   PubMed Web of Science ®Google Scholar
• Boulate G, Amazit L, Naman A, et al. Potentiation of mitotane action by rosuvastatin: new insights for adrenocortical carcinoma management. Int.J.Oncol. 2019;54(6):2149–2156.
   PubMed Web of Science ®Google Scholar
• Kroiss M, Sbiera S, Kendl S, et al. Drug synergism of proteasome inhibitors and mitotane by complementary activation of ER stress in adrenocortical carcinoma cells. Horm.Cancer. 2016;7(5–6):345–355.
   PubMed Web of Science ®Google Scholar
• Ruggiero C, Doghman-Bouguerra M, Ronco C, et al. The GRP78/BiP inhibitor HA15 synergizes with mitotane action against adrenocortical carcinoma cells through convergent activation of ER stress pathways. Mol.Cell.Endocrinol. 2018;474:57–64.
   PubMed Web of Science ®Google Scholar
• Warde KM, Schoenmakers E, Ribes Martinez E, et al. Liver X receptor inhibition potentiates mitotane-induced adrenotoxicity in ACC. Endocr.Relat.Cancer. 2020;27(6):361–373.
   PubMed Web of Science ®Google Scholar
• Subramanian C, Kuai R, Zhu Q, et al. Synthetic high-density lipoprotein nanoparticles: a novel therapeutic strategy for adrenocortical carcinomas. Surgery. 2016;159(1):284–294.
   PubMed Web of Science ®Google Scholar
• Sbiera S, Kendl S, Weigand I, et al. Hsp90 inhibition in adrenocortical carcinoma: limited drug synergism with mitotane. Mol.Cell.Endocrinol. 2019;480:36–41.
   PubMed Web of Science ®Google Scholar