Advanced or Metastatic Adrenal Cancer Regimen: Etoposide + Doxorubicin + Cisplatin + Mitotane (EDP-M)
Fassnacht M et al. N Engl J Med 2012;366:2189–2197
Mitotane 500–5000 mg/day; administer orally, continually
If possible, mitotane is started a minimum of 1 week before cytotoxic treatment is initiated. The ultimate goal is to attain mitotane concentrations in blood of 14–20 mcg/mL over time, as tolerated, trying not to exceed these values as side effects worsen with higher values. Note that side effects may preclude this range from being attained
Initiate treatment with doses of 1000–1500 mg per day at bedtime to minimize sedative effects during waking hours, and escalate doses as tolerated
Large daily doses may be divided in ≥2 doses
Doxorubicin 40 mg/m2; administer by intravenous injection over 3–5 minutes on day 1, every 4 weeks (total dosage/cycle = 40 mg/m2)
Prehydration for cisplatin: ≥500 mL 0.9% sodium chloride injection (0.9% NS) per day; administer intravenously at ≥100 mL/hour for 2 consecutive days, starting before cisplatin on days 3 and 4
Cisplatin 40 mg/m2 per day; administer intravenously in 50–500 mL of 0.9% NS over 30–60 minutes for 2 doses on 2 consecutive days, days 3 and 4, every 4 weeks (total dosage/cycle = 80 mg/m2)
Posthydration for cisplatin: ≥500 mL 0.9% NS per day; administer intravenously at ≥100 mL/hour for 2 consecutive days, after cisplatin on days 3 and 4. Encourage increased oral fluid intake. Monitor and replace magnesium and electrolytes as needed
± Mannitol diuresis: May be given to patients who have received adequate hydration
Mannitol 12.5–25 g may be administered by intravenous injection before or during cisplatin administration, or
Mannitol 10–40 g; administer intravenously over 1–4 hours before or during cisplatin administration, or may be prepared as an admixture with cisplatin
Note: Diuresis with mannitol requires maintaining hydration with intravenously administered fluid during and for hours after mannitol administration
Etoposide 100 mg/m2 per dose; administer intravenously diluted to a concentration within the range 0.2–0.4 mg/mL in 5% dextrose injection or 0.9% NS over at least 60 minutes for 3 consecutive days, on days 2, 3, and 4, every 4 weeks (total dosage/cycle = 300 mg/m2)
Glucocorticoid replacement is necessary in all patients taking mitotane
Hydrocortisone 15–20 mg orally every morning, plus:
Hydrocortisone 7.5–10 mg orally every evening
Mineralocorticoid replacement is also recommended:
Fludrocortisone acetate 100–200 mcg/day orally every morning, or:
Fludrocortisone acetate 100 mcg/day orally every morning and every evening
Supportive Care
Antiemetic prophylaxis
Emetogenic potential on day 1: MODERATE
Emetogenic potential on day 2: LOW
Emetogenic potential on days 3 and 4: HIGH. Potential for delayed symptoms
See Chapter 39 for antiemetic recommendations
Hematopoietic growth factor (CSF) prophylaxis
Primary prophylaxis is NOT indicated
See Chapter 43 for more information
Antimicrobial prophylaxis
Risk of fever and neutropenia is LOW
Antimicrobial primary prophylaxis to be considered:
See Chapter 47 for more information
Patient Population Studied