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Updated: May 8, 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 study evaluating the toxicity and efficacy of single-agent temsirolimus in chemotherapy-naïve
K Kruczek1, M Ratterman, K Tolzien
1Department of Medicine, Advocate Lutheran General Hospital, Park Ridge, IL, USA.
Background:
The mammalian target of rapamycin (mTOR) pathway is deregulated in castration-resistant prostate cancer (CRPC). We investigated the efficacy and toxicity of temsirolimus, an mTOR inhibitor, in chemotherapy-naïve CRPC.
Methods:
In this phase II open label study, eligible patients received IV temsirolimus at 25 mg weekly until objective disease progression, unacceptable toxicity or investigator's discretion. Toxicity was assessed every 4 weeks and responses every 8 weeks. Primary end point was calculating the overall response (OR) rate as well as measuring stable disease (SD) to assess the overall clinical benefit calculated as OR+SD. Secondary end points included prostatic-specific antigen (PSA) changes and time to progression biochemically and radiographically. Correlative studies included prospective assessment of quality of life (QoL) using two previously validated scales.
Results:
Although the sponsor halted the study early, 21 patients were enrolled of which, 15 were evaluable for efficacy and OR. Median age was 74 (range: 57-89), median PSA was 237.5 ng ml(-1) (range: 8.2-2360), visceral disease present in 11 patients (52%), and 17 patients (81%) patients had Gleason score (7-10). Two patients had a partial response (PR) and eight had SD. The OR was 13% (2/15) and the overall clinical benefit (OR+SD) was 67% (10/15). Median time to radiographic disease progression was 2 months (range 2-10 months). Biochemical response assessment was available for 14/15 patients. Any PSA decline was observed in four patients (28.5%; 4/14) with one patient (7%) having >50% PSA decline. Median time to progression by PSA was 2 months (range 1-10 months). With a median follow-up of 32 months, median overall survival (OS) was 13 months (range: 2-37) and three patients remain alive at the data cutoff (5/2013) for an OS of 14% at 4 years on an intent-to-treat analysis. Major non-haematologic toxicities included fatigue (19%) and pneumonia (14%). Main laboratory toxicities included hyperglycaemia (24%) and hypophosphatemia (14%). Also, 52% of enrolled patients had serious adverse events. Other toxicities were consistent with previously reported adverse events with temsirolimus. Despite these observed adverse events, temsirolimus did not adversely impact QoL.
Conclusion:
Temsirolimus monotherapy has minimal activity in chemotherapy-naïve CRPC.
Insights
Temsirolimus showed minimal efficacy in treating castration-resistant prostate cancer (CRPC) patients who had not received prior chemotherapy. While some patients experienced stable disease, the overall response rate was low, suggesting limited clinical benefit.
Area of Science:
- Oncology
- Pharmacology
Background:
- The mammalian target of rapamycin (mTOR) pathway is frequently dysregulated in castration-resistant prostate cancer (CRPC).
- Investigating novel therapeutic targets is crucial for improving outcomes in CRPC.
Purpose of the Study:
- To evaluate the efficacy and toxicity of temsirolimus, an mTOR inhibitor, in patients with chemotherapy-naïve CRPC.
- To assess the overall response rate and clinical benefit of temsirolimus monotherapy.
Main Methods:
- A phase II, open-label study involving 21 patients with chemotherapy-naïve CRPC.
- Patients received intravenous temsirolimus at 25 mg weekly until disease progression or unacceptable toxicity.
- Efficacy was assessed by objective response (OR), stable disease (SD), prostate-specific antigen (PSA) changes, and time to progression.
Main Results:
- Fifteen patients were evaluable for efficacy; 2 (13%) had a partial response, and 8 (53%) had stable disease, yielding an overall clinical benefit (OR+SD) of 67%.
- Median time to radiographic disease progression was 2 months; 7% of patients achieved >50% PSA decline.
- Median overall survival was 13 months, with common toxicities including fatigue, pneumonia, hyperglycemia, and hypophosphatemia.
Conclusions:
- Temsirolimus monotherapy demonstrated minimal activity in chemotherapy-naïve CRPC.
- The observed toxicities were consistent with known adverse events of temsirolimus, and quality of life was not adversely impacted.
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