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Related Experiment Videos

Temsirolimus.

Wen W Ma1, Antonio Jimeno

  • 1Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins, Baltimore, Maryland 21231-1000, USA.

Drugs of Today (Barcelona, Spain : 1998)
|November 8, 2007
PubMed
Summary
This summary is machine-generated.

Temsirolimus, an mTOR inhibitor, shows anti-cancer effects by stopping cell growth and blood vessel formation. While effective, higher doses increase toxicities, impacting treatment tolerance in patients.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • The PI3k/Akt/mTOR pathway is crucial in cancer development.
  • Temsirolimus is a synthetic rapamycin ester inhibiting the mTOR protein.
  • mTOR inhibition leads to cell cycle arrest, antiangiogenesis, and apoptosis.

Purpose of the Study:

  • To evaluate the antitumor effects and toxicity of temsirolimus.
  • To determine optimal dosing for phase I trials.
  • To assess temsirolimus's efficacy in advanced cancers.

Main Methods:

  • In vitro studies on cancer cell lines.
  • In vivo xenograft models.
  • Phase I trials with flat intravenous dosing (25, 75, 250 mg weekly).
  • Phase III randomized trial comparing temsirolimus, interferon, or combination therapy.

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Main Results:

  • Temsirolimus demonstrated significant in vitro antitumor activity and in vivo cytostatic effects.
  • Biological activity was observed across all tested doses.
  • Increased doses correlated with higher frequency and intensity of toxicities (rash, mucositis, diarrhea, hyperlipidemia, hyperglycemia, thrombocytopenia).
  • Temsirolimus monotherapy improved survival in poor-risk clear-cell renal cell carcinoma patients compared to interferon alone in a Phase III trial.

Conclusions:

  • Temsirolimus exhibits significant anti-cancer activity through mTOR inhibition.
  • Dose escalation leads to increased toxicity, necessitating careful management.
  • Temsirolimus offers a survival benefit in specific patient populations, particularly clear-cell renal cell carcinoma.
  • Further research is needed to identify predictive biomarkers for temsirolimus efficacy.