Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2007) 14 P126

ECE2007 Poster Presentations (1) (659 abstracts)

Clinical and biochemical effects of adjuvant mitotane treatment in patients with adrenocortical cancer (ACC)

Fulvia Daffara 1 , Silvia De Francia 2 , Giuseppe Reimondo 1 , Barbara Zaggia 1 , Paola Sperone 3 , Francesco Di Carlo 2 , Alberto Angeli 1 , Alfredo Berruti 3 & Massimo Terzolo 1

1Dipartimento di Scienze Cliniche e Biologiche - Medicina Interna I, ASO San Luigi, Orbassano, Italy, 2Dipartimento di Scienze Cliniche e Biologiche - Laboratorio di Farmacologia, ASO San Luigi, Orbassano, Italy, 3Dipartimento di Scienze Cliniche e Biologiche - Oncologia Medica, ASO San Luigi, Orbassano, Italy.

Objective: Seventeen patients (9 women, 8 men aged 36 years, 22–58) radically resected for ACC were treated with adjuvant mitotane and prospectically followed from 2000 to 2006.

Methods: Stage of ACC: was: 1 stage I,; 12 stage II, 4 stage III; Weiss score 6, 3–9; Ki67% 20, 4–67. Eleven patients had functional tumors. Median duration of treatment was 15 months (range:4–84) and 14 patients are currently on mitotane, 2 died, 1 discontinued treatment after 5 years. All patients were treated with a low-dose regimen (till to 3–4 g/die) and underwent monitoring of plasma mitotane level every 3 months. None of the patients discontinued mitotane definitively for side effects and 16/17 patients reached the therapeutic levels after a median time of 3 months. At the last follow up, 6/17 (35%) patients have relapsed, 15 patients are still alive.

Results: Hyperprolactinemia was observed in 50% of men and 40% of women, 62% of men become partially hypogonadic: reduction of free testosterone was greater than total testosterone. Central hypothyroidism developed in 9 patients who were treated, while 4 patients already on thyroxine required dose increment. Fifteen patients developed overt hypoadrenalism, while 1 patient showed normal cortisol and elevated ACTH, 11 patients developed hypoaldosteronism. Total cholesterol level were slightly enhanced with increase of HDL and reduction of LDL, triglicerides were normal. Reduction of folate level and consequent increase of homocysteine was also observed. Mitotane levels were inversely correlated with cortisol (P=0.007), aldosterone (P=0.01) and FT4 levels (P=0.03), while they were positively correlated with PRA (P=0.004) and HDL levels (P=0.005).

Conclusions: In conclusion, a low-dose regimen of adjuvant mitotane is well tolerated and able to reach the therapeutic interval. Adequate supplementation of adrenal and sex steroid and thyroid hormones is necessary. Some effects of mitotane may be ascribed to either adrenolytic or estrogen-like actions of the drug.

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