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Updated: Jun 30, 2026
Development and Application of Rapamycin-regulated Tyrosine Phosphatases
Published on: September 6, 2024
Pilot study of rapamycin in patients with hormone-refractory prostate cancer
Robert J Amato1, Jaroslaw Jac, Taqi Mohammad
1University of Texas Health Science Center, Memorial Hermann Hospital, Houston, TX 77030, USA. ramato@uth.tmc.edu
Background:
Currently, no second-line treatment exists for hormonerefractory prostate cancer (HRPC) cases that fail docetaxel regimens. Rapamycin, an immunosuppressive macrolide, inhibits metastatic prostate tumor growth and angiogenesis in in vivo mouse models. This pilot study assessed the antitumor activity, safety, and toxicity of rapamycin in patients with HRPC.
Patients And Methods:
Eligible patients had HRPC and disease progression. The initial dose of rapamycin was 0.15 mg/kg followed by 0.04 mg/kg daily without interruption. Rapamycin levels were measured every 28 days with dose adjustments of 0.04-0.06 mg/kg as necessary to maintain levels between 6-10 ng/mL. Patients were evaluated every 4 weeks for prostate-specific antigen (PSA) and safety and every 8 weeks for radiographic response.
Results:
Thirteen patients were enrolled from January 2005 to February 2006. One was not evaluable for response. Responses were seen in 2 of 12 evaluable patients (17%). One patient experienced a 50% decrease in absolute PSA and partial radiographic response; another experienced a PSA response only. Four patients had stable disease (33%). The median progression-free survival was 4.2 months (range, 1.9-23.3 months), and overall survival was 23.3+ months (range, 1.9-34.3+ months). Diarrhea (69%), fatigue (46%), and nausea (46%) were the most common adverse events. Rapamycin was well tolerated and showed signs of antitumor activity.
Conclusion:
Rapamycin and other inhibitors of mammalian targets of rapamycin warrant further study in developing combination therapies with chemotherapy or radiation.
Insights
This study investigated rapamycin as a second-line treatment for hormone-refractory prostate cancer (HRPC). Rapamycin showed antitumor activity and was well tolerated, suggesting potential for combination therapies in advanced prostate cancer.
Area of Science:
- Oncology
- Pharmacology
Background:
- Hormone-refractory prostate cancer (HRPC) lacks effective second-line treatments after docetaxel failure.
- Rapamycin demonstrates anti-tumor and anti-angiogenic effects in preclinical prostate cancer models.
Purpose of the Study:
- To evaluate the antitumor activity, safety, and toxicity of rapamycin in patients with HRPC.
- To establish appropriate dosing for rapamycin in this patient population.
Main Methods:
- A pilot study involving 13 patients with HRPC and disease progression.
- Dosing initiated at 0.15 mg/kg, then 0.04 mg/kg daily, with adjustments to maintain rapamycin levels between 6-10 ng/mL.
- Regular monitoring of prostate-specific antigen (PSA), safety, and radiographic response.
Main Results:
- Two of 12 evaluable patients (17%) showed responses, including one with a 50% PSA decrease and partial radiographic response.
- Four patients (33%) achieved stable disease.
- Median progression-free survival was 4.2 months; median overall survival was 23.3+ months. Common adverse events included diarrhea, fatigue, and nausea.
Conclusions:
- Rapamycin exhibits antitumor activity and is well-tolerated in HRPC patients.
- Further investigation of rapamycin and mTOR inhibitors in combination therapies for prostate cancer is warranted.
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