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The Clinical Application of Tumor Treating Fields Therapy in Glioblastoma

The Clinical Application of Tumor Treating Fields Therapy in Glioblastoma

Published on: April 16, 2019

Practical treatment using mitotane for adrenocortical carcinoma.

Massimo Terzolo¹, Barbara Zaggia, Barbara Allasino

¹aInternal Medicine I bPharmacology, Department of Clinical and Biological Sciences, University of Turin, Italy.

Current Opinion in Endocrinology, Diabetes, and Obesity

|April 16, 2014

Summary

Mitotane effectively treats advanced adrenocortical carcinoma and aids recovery post-surgery. Maintaining optimal mitotane levels (14-20 µg/l) is crucial for efficacy and managing drug interactions, especially with steroid replacement.

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Area of Science:

Endocrinology
Pharmacology
Oncology

Background:

Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine tumor.
Mitotane is a key therapeutic agent for ACC, but its precise mechanisms and optimal use require further elucidation.

Purpose of the Study:

To describe novel findings on mitotane's mechanism of action.
To evaluate mitotane's efficacy as an adjunctive postoperative measure.
To assess mitotane's role in treating advanced adrenocortical carcinoma.

Main Methods:

In-vitro studies investigating mitotane's effects on steroidogenesis.
Retrospective analyses of patient data on recurrence-free survival.
Pharmacokinetic assessments to confirm therapeutic windows and dose-concentration relationships.

Main Results:

Mitotane suppresses steroidogenic pathway gene transcription.
Mitotane induces CYP3A4, increasing metabolic clearance of drugs, including steroids.
Adjunctive mitotane use is associated with prolonged recurrence-free survival.
A therapeutic window for mitotane plasma concentrations was confirmed, though dose-concentration relationship is variable.
Genetic variability influences mitotane metabolism and individual responses.

Conclusions:

Maintain mitotane plasma concentrations of 14-20 µg/l for both adjunctive and monotherapy settings.
Initiate mitotane with a high-dose regimen for monotherapy in advanced ACC.
Anticipate and manage pharmacologic interactions, including increased steroid replacement needs, due to mitotane-induced drug metabolism.
Consider genetic factors influencing mitotane metabolism for personalized treatment approaches.