Mitotane is an inhibitor of adrenal steroidogenesis with cytostatic activity used in the adjuvant and palliative treatment of adrenocortical cancer. Evidence shows that achieving a therapeutic range of between 14 and 20 mg/l is associated with optimal disease control whereas blood levels above this can result in more severe gastrointestinal and neurological toxicity. Therapeutic drug monitoring is available but in real life achieving and remaining within the ideal range can be difficult. Various guidelines recommend different starting doses, does escalation schedules and monitoring frequencies. In addition, body fat content may influence the speed in which optimal blood levels can be obtained. We performed a retrospective case note review of all patients within the West Yorkshire Neuroendocrine Tumour Service treated with mitotane between 2010 and 2018. In our cohort of 21 patients 10 (50%) of patients were started on 12 g/day, 5 (25%) on 3 g/day and 5 (25%) on 47 g/day. The average duration of treatment was 15 months (range 338). The mean time required to achieve a plasma level > 10 mg/l was 4 months (range 18 m) and to achieve therapeutic range 5.6 months (range 212 m). 6/21 patients failed to reach the therapeutic range. In the 21 patients the mean percentage of treatment course spent above 10 mg/l was 42%; within the therapeutic range was 20% and above the therapeutic range was 5%. There appeared to be no significant association between time to achieving the therapeutic range or time spent in therapeutic range and body mass index. The main reasons for stopping treatment were toxicity, rapid disease progression or completion of adjuvant treatment. No definite correlation between duration of therapeutic mitotane concentration and outcome could be determined in this small and heterogeneous cohort.
02 Dec 2019
UK and Ireland Neuroendocrine Tumour Society