Table 2.

Summary of pharmacologic therapies for Cushing’s disease (28, 30, 31, 55, 71, 75–80).

Name	Dose	Route	Mechanism of action	Efficacy to normalize urine free cortisol (%)	Responders characteristics	Tumor size reduction	Side effects	Comments
Pasireotide	600–900 μg twice daily	Subcutaneous	Agonist SSTR5 > 2	30–40	UFC < 5× ULN	25–80%	GI and biliary issues Hyperglycemia QT prolongation	Only drug approved for CD
Pasireotide LAR	10–30 mg monthly	Intramuscular		30–50	UFC < 2× ULN	10–20%
Cabergoline	0.5–6 mg weekly (in divided doses)	Oral	Dopamine agonist (D2)	25–40	Small subgroup of corticotrophs adenomas expressing D2 receptor	N/A	Hypotension Nausea Headache	Usually short-term response
Temozolomide	150–200 mg/m2/day ×5 days monthly	Oral	Methylation DNA	80	Possibly patients with negative MGMT mutation	0 (stable)–50% for most patients; rarely patients had progressive tumor growth	GI issues Headache Dizziness Hearing loss	Aggressive adenomas or carcinomas
Roscovitine	400 mg twice daily	Oral	Inhibition CDK/cyclin E	N/A	N/A	N/A	Preliminary: Asthenia Nausea Vomiting Hypokaliemia	Phase II study ongoing
Retinoic acid	80 mg once a day	Oral	Agonist RAR	25	Absence of COUP-TF1	N/A	Mucositis Photosensitivity Hypertriglyceridemia	Based on small studies
Gefitinib	250 mg once a day	Oral	Inhibition EGFR	N/A	USP8-mutated adenomas	N/A	Skin reaction Diarrhea Interstitial pneumonitis	Phase II study ongoing
Silibinin	To be determined	To be determined	Inhibition HSP90	N/A	N/A	N/A	Minimal	Animal studies only

N/A, not available; HSP90, heat shock protein 90; USP8, ubiquitin-specific protease 8; EGFR, epidermal growth factor receptor; CDK, cyclin-dependant kinase; UFC, urinary free cortisol; ULN, upper limit of normal; RAR, retinoic acid receptor; COUP-TF1, chicken ovalbumin upstream promoter transcription factor-1.