Class / Mechanism
- mTOR = mammalian target of rapamycin, a serine-threonine kinase regulating cell growth, proliferation, metabolism, and angiogenesis.
- Inhibition → ↓ protein synthesis, ↓ angiogenesis, ↓ cell cycle progression.
- Pathway: PI3K → AKT → mTOR → cell growth/survival.
- Cancer link: Overactive PI3K/AKT/mTOR signaling in many tumors.
Main Agents
| Drug | Brand |
|---|---|
| Sirolimus (Rapamune®) | Immunosuppressant (transplant); not used in oncology directly. |
| Temsirolimus (Torisel®) | IV; prodrug of sirolimus; mainly for renal cell carcinoma (RCC). |
| Everolimus (Afinitor®) | Oral; used in RCC, breast cancer (HR+/HER2–), pancreatic NETs, subependymal giant cell astrocytoma (SEGA), tuberous sclerosis. |
Oncology Indications
- Renal cell carcinoma (RCC).
- Breast cancer (HR+, HER2–, postmenopausal, often with exemestane).
- Pancreatic neuroendocrine tumors (PNETs).
- Subependymal giant cell astrocytoma (SEGA) and tuberous sclerosis–associated renal angiomyolipoma.
- Other solid tumors (off-label trials).
Toxicities (Class Effects)
🔹 Mucositis/Stomatitis – very common (often dose-limiting).
🔹 Rash, acneiform eruptions.
🔹 Hyperglycemia, hyperlipidemia (metabolic toxicities).
🔹 Myelosuppression (esp. anemia, thrombocytopenia).
🔹 Non-infectious pneumonitis (unique class toxicity, can be severe).
🔹 Immunosuppression → infections (oral, pulmonary, viral reactivation).
🔹 Delayed wound healing.
Pharmacist Considerations
- Monitor labs: glucose, lipids, CBC, renal/hepatic function.
- Stomatitis prophylaxis: dexamethasone mouth rinse may reduce incidence/severity.
- Infection risk: screen for HBV, monitor for pneumonia symptoms.
- Drug interactions: CYP3A4 and P-gp substrates → avoid strong inhibitors/inducers (azole antifungals, rifampin, clarithromycin).
- Hold for surgery (due to delayed wound healing).
- Adjust dose in hepatic impairment.
Quick Clinical Pearl
- Temsirolimus (IV) → premedicate with diphenhydramine to prevent hypersensitivity (contains polysorbate 80).
- Everolimus (oral) → more common in solid tumor oncology; stomatitis and hyperglycemia are big issues.