Adrenal Carcinoma Medication

Updated: Dec 06, 2022
  • Author: Bagi RP Jana, MD, MBA, MHA, FACP; Chief Editor: Lawrence T Kim, MD, FACS, FACE  more...
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Medication Summary

Adjuvant or palliative treatment for adrenocortical carcinoma (AC) has been studied by using mitotane, cisplatin, etoposide, and doxorubicin. Mitotane leads to autodestruction of the adrenal cortex. Therefore, it is used in almost all protocols in the hope that it will decrease any autonomous hormone production and suppress tumor growth. Chemotherapy has focused on 3 antineoplastics—cisplatin, etoposide, and doxorubicin—given alone or in combination; studies have focused on the regimen etoposide and cisplatin and on etoposide, doxorubicin, and cisplatin.


Chemotherapeutic Agents

Class Summary

These agents inhibit cell growth and proliferation. Cancer chemotherapy is based on an understanding of tumor cell growth and how drugs affect it. After cells divide, they enter a period of growth (phase G1), followed by DNA synthesis (phase S). The next phase is a premitotic phase (phase G2). Finally, a period of mitotic cell division (phase M) occurs.

Rates of cell division vary for different tumors. Most common cancers grow slowly compared with normal tissues, and the rate may decrease if tumors are large. This difference allows healthy cells to recover from chemotherapy more quickly than do malignant cells, and this is the rationale for current cyclic dosage schedules.

In interfering with cell reproduction, some antineoplastic agents are specific to certain phases of the cell cycle, whereas others (eg, alkylating agents, anthracyclines, cisplatin) are not phase specific. Cellular apoptosis (ie, programmed cell death) is another potential mechanism of many antineoplastic agents.

Mitotane (Lysodren)

Mitotane is an option for the management of AC because it is a relatively specific adrenocortical cytotoxin. It decreases the production of cortisol by causing adrenal atrophy and affecting mitochondria in adrenocortical cells. No pediatric standards or dosages have been established; doses in children must be individualized.


Cisplatin inhibits DNA synthesis and, therefore, cell proliferation, by causing DNA cross-linking and denaturation of the double helix.

Doxorubicin (Adriamycin)

Doxorubicin, a cytotoxic anthracycline antibiotic isolated from cultures of Streptomyces peucetius var. caesius, is mutagenic and carcinogenic. It blocks DNA and RNA synthesis by inserting between adjacent base pairs and binding to the sugar-phosphate backbone of DNA, inhibiting DNA polymerase. The drug binds to nucleic acids presumably by specific intercalation of the anthracycline nucleus with the DNA double helix. It can also cause DNA strand breakage, because of its effects on topoisomerase II.

Doxorubicin is a powerful iron chelator; the iron-doxorubicin complex induces the production of free radicals that can destroy DNA and cancer cells.

Doxorubicin's maximum toxicity occurs during the S phase of cell cycle. The drug has a multiphasic disappearance curve, with half-lives of up to 30 hours. This agent does not cross blood-brain barrier but is taken up rapidly by the heart, lungs, liver, kidney, and spleen. The dosage is related to body surface area.

Antiproliferative drugs may be useful for palliating symptoms in patients with diffuse metastases. Liposomes in different drug products can vary in chemical and physical properties, which can substantially affect functional properties.

Etoposide (Toposar)

Etoposide is a glycosidic derivative of podophyllotoxin that exerts a cytotoxic effect by stabilizing the normally transient covalent intermediates formed between the DNA substrate and topoisomerase II. The drug leads to single-stranded and double-stranded DNA breaks that arrest cellular proliferation in the late S or early G2 phase of cell cycle.


PD-1/PD-L1 Inhibitors