[Therapy of the adrenocortical carcinoma with Lysodren (o,p'-DDD). Therapeutic management by monitoring o,p'-DDD blood levels].
BACKGROUND
o,p'-DDD (1-dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)-ethane), which leads to a cytotoxic necrosis of the adrenal glands, currently is therapy of choice for metastasized adrenocortical carcinomas. Clinical experience is still poor, but most studies demonstrate an increment of survival time in patients treated with o,p'-DDD after incomplete surgery. The therapeutic range is close and therefore dosage is difficult, mainly based on clinical signs. Methods for routine determination of o,p'-DDD are not yet broadly available.


METHODS
We developed a method for the determination of o,p'-DDD and report our experience with the monitoring of serum levels of o,p'-DDD in our patients. Nine patients have been included, eight patients with metastasized adrenocortical carcinoma were treated with o,p'-DDD.


RESULTS
At time of evaluation six of eight patients had deceased, 27.9 +/- 25.1 months after recurrence of the disease. Time of survival for all patients was 28.2 +/- 22.0 months since diagnosis of recurrence. In three patients the target dose of 9-10 g/d could not be reached due to the clinical situation. The serum levels of these patients were low (6.3 +/- 4.2 micrograms/ml). Mean survival time was significantly longer for those patients who reached serum levels above 14 micrograms/ml in comparison to those who failed to reach such high levels (41.3 +/- 16.2 vs 6.3 +/- 3.6 months, p < 0.01). The dose which was necessary to reach high levels was individually different. All patients developed adrenocortical insufficiency. Other side effects were fatigue (seven patients), gastrointestinal problems and elevated liver enzymes (six patients each), changes in blood count (five patients) and central nervous disorder (four patients). All patients developing intolerable side effects had very high serum levels of o,p'-DDD (> 20 micrograms/ml).


CONCLUSIONS
Our data confirm that the efficacy of a therapy with o,p'-DDD as well as the risk to develop intolerable side effects depend on the serum levels of o,p'-DDD. Monitoring of o,p'-DDD therapy by measuring serum levels of o,p'-DDD helps to adapt this therapy individually, avoiding serious side effects as well as to realize antitherapeutical resistance. Determination of o,p'-DDD serum levels helps to decide over intensification or cessation of therapy.
Heilmann
P
P
Abteilung für Innere Medizin I, Endokrinologie und Stoffwechsel, Universitätsklinikum Heidelberg. Peter_Heilmann@med.uni-heidelberg.de
Wagner
P
P
Nawroth
P P
PP
Ziegler
R
R
D000306:Adrenal Cortex Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000556:secondary / Q000601:surgery; D018268:Adrenocortical Carcinoma / Q000097:blood / Q000188:drug therapy* / Q000556:secondary / Q000601:surgery; D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008939:Mitotane / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D009364:Neoplasm Recurrence, Local; D016019:Survival Analysis; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D008939:Mitotane