THERAPEUTICS

Brands

• Afinitor, Afinitor Disperz, Zortress, Certican

Generic?

• No

Class

• Immunosuppressant, antineoplastic agent

Commonly Prescribed for

(FDA approved in bold)

• Patients with subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis complex (TSC) who require therapeutic intervention but are not candidates for curative surgical resection in adults or children 1 year and older (Afinitor or Afinitor Disperz only)

• Adults with renal angiomyolipoma and TSC not requiring immediate surgery. (Afinitor only)

• Adults with progressive neuroendocrine tumors of pancreatic origin (PNET) that are unresectable, locally advanced, or metastatic (Afinitor only)

• Advanced renal cell carcinoma (RCC), failure to sunitinib or sorafenib (Afinitor only)

• Prophylaxis of organ rejection in adult patients undergoing kidney or liver transplantation (Zortress only)

• Postmenopausal women with advanced hormone receptor-positive, HER2- negative breast cancer in combination with exemestane after failure of treatment with letrozole or anastrozole (Afinitor only)

• Brainstem glioma

How the Drug Works

• A macrolide lactam that works as a mammalian target of rapamycin (mTOR) inhibitor by binding to the FK506 binding protein-12. It blocks the cell progression from G1 to S phase, causing apoptosis and cell death. It also inhibits hypoxia-inducible factor that subsequently decreases vascular endothelial growth factor. Overall, it inhibits cell proliferation, angiogenesis, and glucose uptake. Also, in TSC subjects, everolimus inhibits two regulators of mTORC1 signaling that are the oncogene suppressors harmatin (TSC1) and tuberin (TSC2)

How Long Until It Works

• Immunosuppression: usually within 1 week

• Tumor suppression: usually more than 1 month

If It Works

• Continue treatment if tolerated and effective. Monitor any adverse event

If It Doesn't Work

• Check drug concentration. Adjust dose if necessary. Consider surgical referral. Switch to other agents when needed

Best Augmenting Combos for Partial Response or Treatment-Resistance

• Combine with other immunosuppressive agents or antineoplastic agents