Mitotane for Adrenocortical Carcinoma: Dosing Guidelines and Therapeutic Drug Monitoring

　　1.Pre-Treatment Assessment

　　Before initiating mitotane therapy,a comprehensive baseline evaluation is essential.This typically includes liver function tests,complete blood count,renal function assessment,and endocrine hormone profiling.Pre-menopausal women should also undergo pelvic ultrasound examination.The patient's overall performance status and comorbidities must be assessed to guide individualized dose planning.

　　2.Recommended Dosage and Administration

　　Mitotane is available as 500 mg oral tablets that must be swallowed whole—they should not be split,chewed,or crushed.The recommended initial dose is 2 to 6 grams per day,divided into 3 to 4 doses taken with meals.Consuming the medication with fatty foods can significantly enhance bioavailability.The dose is then gradually escalated based on tolerability and plasma drug levels,with most patients reaching a maintenance dose of approximately 9 to 10 grams per day.

　　3.Importance of Therapeutic Drug Monitoring

　　Mitotane is highly lipophilic with an elimination half-life ranging from 18 to 159 days,resulting in significant inter-individual pharmacokinetic variability.The recommended therapeutic window for plasma trough concentration is 14 to 20 mg/L.Concentrations below 14 mg/L are associated with insufficient antitumor efficacy,while levels exceeding 20 mg/L markedly increase the risk of neurotoxicity.Since steady-state concentrations typically require 3 to 5 months to achieve,plasma levels should be monitored every 3 to 4 weeks during the initial phase and every 6 to 12 weeks once stable.

　　4.Hormone Replacement and Precautions

　　Mitotane induces adrenal cortex atrophy;therefore,all patients must receive concurrent glucocorticoid replacement therapy(e.g.,hydrocortisone),often at doses higher than standard physiological replacement.Patients should strictly adhere to the prescribed regimen and never adjust doses or discontinue therapy without medical guidance.Regular monitoring of liver function,blood counts,and endocrine parameters is essential throughout treatment.Common adverse effects include gastrointestinal disturbances(nausea,vomiting,diarrhea),neurological symptoms(dizziness,somnolence,ataxia),and generalized fatigue.Any severe or worsening symptoms should be promptly reported to the treating physician.

　　5.Summary

　　As the only globally approved systemic agent for adrenocortical carcinoma,mitotane's efficacy and safety depend heavily on structured dose titration and ongoing therapeutic drug monitoring.An individualized approach combined with multidisciplinary management helps maximize antitumor benefit while minimizing toxicity risks.