Quando l’oncologo ha bisogno
dell’endocrinologo
Topics
• Tumori del surrene
Carcinoma della corteccia surrenalica
Incidenza 0,5-2/1.000.000/anno
Picco bimodale in età pediatrica e tra la 4° e la
5° decade
Rapporto maschi/femmine 1,5/1
Per lo piu’ sporadico
Li-Fraumeni
MEN-1
Congenital adrenal hyperplasia
Familial polyposi colon
Carcinoma della corteccia surrenalica:
60-65% funzionanti
•
•
•
•
Cushing
Virilizzazione
Femminizzazione
Iperaldosteronismo
Carcinoma corticosurrenalico :
chirurgia
Chemioterapia : mitotane
editorials
Cl
C
Cl
C
Cl
Cl
Cl
P-450
NADPH, O2
Cl
Cl
Cl
−HCl
C
H
H
Cl
C
Cl
C
H
OH
Cl
C
H
O
H2O
O,p'-DDD
(Mitotane)
Cl
Cl
Acylation of
bionucleophiles
C
H
COOH
O,p'-DDA
Figure 1. Metabolism of Mitotane.
RETAKE
1st
AUTHOR: Schteingart
ICM
Mitotane is hydroxylated at the β-carbon
and transformed by dehydrochlorination into
2nd an acyl chloride. The acyl
FIGURE: 1 of 1
REG
F
chloride either covalently binds to bionucleophiles in the target cells or is transformed
3rd to an acetic acid derivative
CASE
Revised
for excretion.
EMail
Enon
ARTIST:
ts
Line
H/T
Combo
4-C
H/T
SIZE
33p9
AUTHOR, PLEASE
NOTE:
in different animal species.6 The dog adrenal,
require
a lengthy, multicenter, international study.
Figure has been redrawn and type has been reset.
which is the most responsive to mitotane, is
alsocheckMeanwhile,
we are left with well-designed, multiPlease
carefully.
the most capable of metabolic transformation and center, retrospective studies such as the one conJOB:
35623
06-07-07
covalent binding. In contrast,
the
human adrenal ducted byISSUE:
Terzolo
et al.1
is less capable of both metabolic transformation
A limitation of mitotane therapy has been its
and covalent binding and is thus less responsive.
marked toxicity at daily doses exceeding 6 g. DosAs depicted in Figure 1, the pathway of mito- es sufficient to achieve “therapeutic” levels of 16
tane metabolism follows the well-known process µg per milliliter are usually associated with unby which chloramphenicol causes toxicity. Mito- desirable toxicity. An important finding in the
tane is hydroxylated at the β-carbon and quickly study by Terzolo et al. is that favorable outcomes
transformed by dehydrochlorination into an acyl were achieved with relatively low doses of mitochloride. The acyl chloride either covalently binds tane — 1 to 3 g per day was sufficient to produce
to bionucleophiles in the target cells or through the desired effect with reduced toxic effects.
loss of water is transformed into an acetic acid
Though physicians who are treating patients
derivative for renal excretion. The initial hydroxyl- with adrenocortical carcinoma may continue to
ation step is carried out in the mitochondria and request randomized clinical trials concerning adcatalyzed by a P-450 enzyme, giving adrenal se- juvant therapy with mitotane, the study by Terzolo
lectivity to the action of mitotane.7 Developing et al. provides the best evidence to date that adcancer cells will vary in their ability to metabolize juvant mitotane treatment for adrenocortical carmitotane because of alterations in this metabolic cinoma has benefit after radical surgery, and it
process. Tumors with an ability to metabolize mi- should make the therapeutic choice of using the
Linee guida ESMO 2012
Chemioterapia : oltre il mitotane
ESMO 2012
Suspected diagnosis
Confirmatory test
Diagnostic test
Preoperative managment
Postoperative management
ESMO 2012
Take home messages
Patologo
Gastroenterologo
Oncologo
Endocrinologo
Radiologo
Interventista
Medico
Nucleare
Chirurgo
Take home messages
Take home messages
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