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Endocrine Abstracts (2013) 31 P57 | DOI: 10.1530/endoabs.31.P57

1Department of Endocrinology, King’s College Hospital, London, UK; 2Department of Radiology, King’s College Hospital, London, UK; 3Department of Histopathology, King’s College Hospital, London, UK; 4Department of Biochemistry, King’s College Hospital, London, UK.


Background: Mitotane is an adrenolytic chemotherapy, currently accepted as first line adjuvant therapy in adrenocortical carcinoma. Mitotane has a narrow therapeutic window. Serum levels of >14 mg/l are required to achieve a cytotoxic effect and levels of >20 mg/l are potentially toxic. There are two strategies for mitotane initiation: a low-dose regimen (3 g) and a high-dose regimen (increase to 6g/day over 4 days and reduce to 4.5 g/day after 10 days).

Methods: We conducted a retrospective review of consecutive mitotane use for adrenocortical carcinoma in a UK tertiary centre from 2006 to 2012. Mitotane initiation was completed using a nurse-led protocol.

Results: Initiation: Twenty patients were identified: 15 were prescribed the high-dose regimen and five the low-dose regimen. Eighty-five percent (17/20) achieved the therapeutic threshold (>14 mg/l). Mean time to reach therapeutic level was 2.2 months. Twenty percent (4/20) achieved therapeutic threshold in the first month. In total, seventy percent (14/20) achieved therapeutic levels within 3 months of initiation. Mitotane levels were performed 2-weekly for the first 3 months. The maximum dose used ranged from 3 to 8 g/day (mean 5.5 g/day).

Maintenance

Of the 20 patients initiated on mitotane, twenty-five percent (5/20) discontinued treatment because of side effects and/or intolerance (neurological and gastrointestinal symptoms). A further twenty-five percent (5/20) discontinued following disease progression with subsequent mortality. In total, seventy-five percent (15/20) of patients continued to maintenance phase (>3 months). Of these, seventy-seven percent of serum mitotane levels were above therapeutic threshold and fifty-three percent were within the range 14–20 mg/l. The mean maintenance dose of mitotane for this group was 4.8 g/day (range 2.5–8.0 g/day). Ten patients currently remain on mitotane.

Conclusion: Initiation of mitotane can be safely performed on an outpatient basis, using a nurse-led protocol. Seventy percent of patients in our series achieved mitotane levels above the therapeutic threshold within 3 months, comparing favourably to other published series.

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