title: High-dose mitotane strategy in adrenocortical carcinoma: prospective analysis of plasma mitotane measurement during the first 3 months of follow-up.
abstract: BACKGROUND
  The benefit-to-risk ratio of a high-dose strategy at the initiation of mitotane treatment of adrenocortical carcinoma (ACC) remains unknown.
  
  
  METHODS
  To evaluate the performance of a high-dose strategy, defined as the highest tolerated dose administered within 2 weeks and maintenance therapy over 4 weeks, we conducted a single-center, prospective study with two main objectives: to evaluate the percentage of patients who achieve a plasma mitotane level above 14 mg/l and to evaluate the tolerance of mitotane within the first 3 months of treatment. Plasma mitotane levels were measured monthly using HPLC.
  
  
  RESULTS
  Twenty-two patients with ACC were prospectively enrolled. The high-dose mitotane strategy (4 g/day or more in all patients, with a median of 6 g/day within 2 weeks) enabled to reach the therapeutic threshold of >14 mg/l at 1, 2, or 3 months in 6/22 patients (27%), 7/22 patients (32%), and 7/22 patients (32%) respectively. In total, a therapeutic plasma mitotane level was reached in 14 out of 22 patients (63.6%) during the first 3 months in ten patients, and after 3 months in four patients. Grade 3-4 neurological or hematological toxicities were observed in three patients (13.6%).
  
  
  CONCLUSIONS
  Employing a high-dose strategy at the time of mitotane initiation enabled therapeutic plasma levels of mitotane to be reached within 1 month in 27% of the total group of patients. If this strategy is adopted, we suggest that mitotane dose is readjusted according to plasma mitotane levels at 1 or/and 2 months and patient tolerance.
authors: Department of Nuclear Medicine and Endocrine Tumors, Institut Gustave Roussy, Univ. Paris Sud, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France.
authors: Sophie
authors: S
authors: Mauclère-Denost
authors: Sophie
authors: S
authors: Leboulleux
authors: Isabelle
authors: I
authors: Borget
authors: Angelo
authors: A
authors: Paci
authors: Jacques
authors: J
authors: Young
authors: Abir
authors: A
authors: Al Ghuzlan
authors: Desiree
authors: D
authors: Deandreis
authors: Laurence
authors: L
authors: Drouard
authors: Antoine
authors: A
authors: Tabarin
authors: Philippe
authors: P
authors: Chanson
authors: Martin
authors: M
authors: Schlumberger
authors: Eric
authors: E
authors: Baudin
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D018268:Adrenocortical Carcinoma / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D001774:Blood Chemical Analysis; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D008939:Mitotane / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood* / Q000493:pharmacokinetics; D009994:Osmolar Concentration; D013997:Time Factors
chemical_list: D018931:Antineoplastic Agents, Hormonal; D008939:Mitotane