- Class: mTOR inhibitor (mechanistic target of rapamycin).
- Type: Intravenous small molecule (prodrug of sirolimus/rapamycin).
Mechanism of Action (MOA)
- Binds to FKBP-12, forming a complex that inhibits mTORC1.
- Blocks downstream signaling (PI3K/AKT/mTOR pathway) → inhibits cell growth, proliferation, angiogenesis, and protein synthesis.
- Causes G1 cell cycle arrest and reduces tumor vascularization.
Clinical Uses
- Advanced renal cell carcinoma (RCC) – poor-risk patients.
- Investigational use in other malignancies: breast cancer, mantle cell lymphoma.
Dosing (Adults)
- 25 mg IV once weekly, infused over 30–60 minutes.
- Dose adjustments:
- Hepatic impairment
- Concomitant strong CYP3A4 inhibitors/inducers
- Premedication not routinely required.
Toxicities
- Hematologic: anemia, thrombocytopenia, leukopenia.
- Metabolic: hyperglycemia, hyperlipidemia.
- Dermatologic: rash, mucositis/stomatitis.
- Fatigue, edema, asthenia.
- Rare: pneumonitis, interstitial lung disease.
- Impaired wound healing – avoid major surgery during therapy.
Monitoring
- CBC with differential.
- Blood glucose, lipid profile.
- Liver function tests.
- Signs of infection or pulmonary toxicity.
- Monitor for edema, weight gain, and wound healing issues.
Summary
Temsirolimus (Torisel®) is an IV mTOR inhibitor used in poor-risk advanced RCC. Key concerns include hematologic toxicity, metabolic disturbances, mucositis, and pneumonitis, requiring regular CBC, metabolic panels, liver function, and monitoring for pulmonary symptoms.