title: Low-dose monitored mitotane treatment achieves the therapeutic range with manageable side effects in patients with adrenocortical cancer.
abstract: Eight patients with adrenocortical cancer were treated with low doses of mitotane (2-3 g daily) while monitoring drug plasma levels. When the mitotane concentrations reached the therapeutic range (defined as mitotane plasma levels between 14-20 microg/mL), a dose reduction was performed to avoid toxicity. Thereafter, the mitotane dose was tailored according to plasma levels. A progressive increase in plasma mitotane concentrations was observed during treatment, and a highly significant linear correlation was found between plasma drug levels and the total mitotane dose. The therapeutic threshold was reached in all patients after 3-5 months and a total mitotane dose of 283-387 g/days (median, 363). The duration of treatment was 8-40 months (median, 9). Toxicity was manageable in all but one patient, who discontinued treatment. It is therefore possible to design a standard low dose schedule, e.g. 3 g/daily for about 3-4 months with following dose adjustments guided by the monitoring of plasma mitotane levels. This approach is able to provide therapeutic mitotane concentrations and limit the unwanted effects. The present data provide a rationale to change the approach to mitotane treatment in patients with adrenocortical carcinoma from high dose to low dose regimens.
authors.affiliation: Dipartimento di Scienze Cliniche e Biologiche, Medicina Interna I, Università di Torino, Italy. terzolo@usa.net
authors.forename: M
authors.initials: M
authors.lastname: Terzolo
authors.forename: A
authors.initials: A
authors.lastname: Pia
authors.forename: A
authors.initials: A
authors.lastname: Berruti
authors.forename: G
authors.initials: G
authors.lastname: Osella
authors.forename: A
authors.initials: A
authors.lastname: Alì
authors.forename: V
authors.initials: V
authors.lastname: Carbone
authors.forename: E
authors.initials: E
authors.lastname: Testa
authors.forename: L
authors.initials: L
authors.lastname: Dogliotti
authors.forename: A
authors.initials: A
authors.lastname: Angeli
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D000324:Adrenocorticotropic Hormone / Q000097:blood; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D002784:Cholesterol / Q000097:blood; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008939:Mitotane / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use*; D009367:Neoplasm Staging; D012044:Regression Analysis; D012189:Retrospective Studies; D014280:Triglycerides / Q000097:blood; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014280:Triglycerides; D008939:Mitotane; D000324:Adrenocorticotropic Hormone; D002784:Cholesterol; D005723:gamma-Glutamyltransferase