Related Experiment Video
Updated: May 10, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
A phase II trial of temsirolimus in men with castration-resistant metastatic prostate cancer
Andrew J Armstrong1, Tong Shen, Susan Halabi
1Duke Cancer Institute and the Duke Prostate Center, Duke University, Durham NC; Department of Medicine, Division of Medical Oncology, Duke University, Durham NC; Department of Surgery, Division of Urology, Duke University, Durham NC; Duke University Medical Center, Duke University, Durham NC.
Background:
Phosphatase and tensin homologue (PTEN) loss is common in advanced prostate cancer, leading to constitutive activation of the PI3 kinase pathway. Temsirolimus blocks mammalian target of rapamycin (mTOR)/target of rapamycin complex 1 (TORC1), a key signaling node in this pathway; its activity in men with advanced castration-resistant metastatic prostate cancer (mCRPC) is unknown.
Methods:
We conducted a single-arm trial of weekly intravenous temsirolimus administration in men with chemorefractory mCRPC who had ≥ 5 circulating tumor cells (CTCs) at baseline. The primary end point was the change in CTCs at 8 weeks; secondary end points were composite progression-free survival (PFS) (excluding prostate-specific antigen [PSA]), PSA and radiographic response rates, safety, and survival. At PSA/CTC progression, an anti-androgen could be added while continuing temsirolimus.
Results:
Eleven patients were accrued out of a planned 20; the trial was stopped prematurely because of lack of efficacy/feasibility. Median age was 61 years, with 55% African-Americans and 36% Caucasian patients. Median baseline PSA level was 390 ng/dL, median baseline number of CTCs was 14 cells; 50% of patients had pain, and 63% had undergone ≥ 2 previous chemotherapy regimens. Median CTC decline was 48% and 3 patients experienced decline in CTCs to < 5. However, 73% of men had a persistently unfavorable number of CTCs (≥ 5) and only 1 patient had a ≥ 30% PSA decline. Median PFS was 1.9 months (95% confidence interval [CI], 0.9-3.1) and median overall survival (OS) was 8.8 months (95% CI, 3.1-15.6). Toxicities included grade 4 hypophosphatemia and central nervous system (CNS) hemorrhage, and frequent grade 3 fatigue, anemia, stomatitis, hypokalemia, weakness, and hyperglycemia.
Conclusion:
Temsirolimus lacked sufficient clinical activity in men with mCRPC, despite transient CTC improvements in some men. Future studies should focus on combination approaches or novel PI3K pathway inhibitors.
Insights
Temsirolimus showed limited efficacy in advanced prostate cancer patients with high circulating tumor cells (CTCs). The drug did not significantly improve progression-free survival or response rates, suggesting combination therapies may be needed.
Area of Science:
- Oncology
- Prostate Cancer Research
- Molecular Targeted Therapy
Background:
- Phosphatase and tensin homologue (PTEN) loss is prevalent in advanced prostate cancer, activating the PI3K pathway.
- Temsirolimus targets the mammalian target of rapamycin (mTOR)/TORC1 signaling pathway, a key component of this cascade.
- The efficacy of temsirolimus in advanced castration-resistant metastatic prostate cancer (mCRPC) was previously unknown.
Purpose of the Study:
- To evaluate the clinical activity of temsirolimus in men with chemorefractory metastatic castration-resistant prostate cancer (mCRPC).
- To assess the impact of temsirolimus on circulating tumor cells (CTCs) and other clinical endpoints in this patient population.
Main Methods:
- A single-arm trial involving weekly intravenous temsirolimus administration.
- Patients with mCRPC and at least 5 circulating tumor cells (CTCs) at baseline were enrolled.
- Primary endpoint was the change in CTCs at 8 weeks; secondary endpoints included progression-free survival (PFS), PSA response, and safety.
Main Results:
- The trial accrued 11 of 20 planned patients and was stopped early due to lack of efficacy.
- Median CTC decline was 48%, but 73% of patients maintained ≥ 5 CTCs.
- Median PFS was 1.9 months, and only one patient showed a ≥ 30% PSA decline.
- Significant toxicities included hypophosphatemia and CNS hemorrhage.
Conclusions:
- Temsirolimus demonstrated insufficient clinical activity in men with mCRPC, despite some transient CTC reductions.
- Future research should explore combination therapies or novel PI3K pathway inhibitors for mCRPC treatment.
- The study highlights the need for more effective strategies targeting the PI3K pathway in advanced prostate cancer.
More Related Videos
08:38Renal Capsule Xenografting and Subcutaneous Pellet Implantation for the Evaluation of Prostate Carcinogenesis and Benign Prostatic Hyperplasia
Published on: August 28, 2013
03:07Single-Port Robotic-assisted Transaxillary Breast-conserving Surgery: A Prospective, Single-arm, Non-randomized Phase IIa Clinical Trial
Published on: August 19, 2025
Related Concept Videos
01:11Clinical Trials: Overview
01:16Clinical Trials
There are four phases in a clinical trial. A phase one...