Systemic chemotherapy (chemo) uses drugs that are given into a vein or by mouth (in pill form). These drugs enter the bloodstream and reach throughout the body, making this treatment useful for cancer that has spread or metastasized to organs beyond the adrenal gland. It is only used for adrenal gland cancer that has become widespread. Chemo does not cure adrenal cancer. It is most often used for adrenal cancer that has spread or come back after surgery

The drug most often used for people with adrenal cortical carcinoma is a drug called mitotane. Mitotane blocks hormone production by the adrenal gland and also destroys adrenal cancer cells. Some studies have shown that starting mitotane treatment when all of the cancer is thought to be gone may delay the return of the cancer. If the cancer has not been completely removed by surgery or has come back, mitotane will shrink the cancer in about 30% of patients. On average, the response lasts about one year. But the response time can be longer for some patients.

Mitotane is particularly helpful for people with adrenal carcinomas who are suffering from the effects of excessive hormone production, Even when it doesn't shrink the tumor, mitotane can reduce abnormal hormone production and relieve symptoms. About 80% of patients with excess hormone secretion are helped by mitotane. This drug can cause major side effects, however. The most common are nausea, vomiting, diarrhea, rashes, and sleepiness. Sometimes lower doses of the drug can still be effective and cause fewer side effects. This drug comes as a pill and is taken 3 to 4 times a day.

Giving mitotane after the cancer is completely removed with surgery may help keep the cancer from growing back. This approach is called adjuvant chemotherapy. It works well for other types of cancer, but has not been studied well in adrenal cortex cancer.