| General information |
| Database: | DB00236 |
| Objective: | The mammalian target of rapamycin (mTOR) pathway is deregulated in castrationresistant prostate cancer (CRPC). They investigated the efficacy and toxicity of temsirolimus, an mTOR inhibitor, in chemotherapyna ve CRPC. |
| Authors: | Kruczek K, et al |
| Title: | a phase II study evaluating the toxicity and efficacy of singleagent temsirolimus in chemotherapyna ve castrationresistant prostate cancer. |
| Journal: | Br J Cancer |
| Year: | 2013 |
| PMID: | 24008662 |
| Trial Design |
| Clinical Trial Id: | NCT00919035 |
| Agent: | temsirolimus
|
| Target: | Serine/threonineprotein kinase mTOR
|
| Cancer Type: | prostate cancer |
| Cancer Subtype: | castrationresistant prostate cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a phase II open label study |
| Key Patients Feature: | Eligible patients were greater than or equal to 18 years of age, with a diagnosis of CRPC per standard definition. Patients had an ECOG performance status of less than or equal to 2 with measurable disease biochemically (using serum prostaticspecific antigen (PSA) measurements, with PSA of at least 5 ng/ml at baseline) and/or radiographically (using bone scans and/or computed tomography of measurable disease areas). Median age was 74 (range: 5789), median PSA was 237.5 ng ml(1) (range: 8.22360), visceral disease present in 11 patients (52%), and 17 patients (81%) patients had Gleason score (710). |
| Biomarker: | PSA |
| Biomark Analysis: | Serum prostatespecific antigen levels were prospectively monitored as a biomarker for cancer activity. |
| Control Group Info: | single arm |
| Treatment Info: | 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: | the overall response (OR) rate as well as measuring stable disease (SD) to assess the overall clinical benefit calculated as OR+SD. |
| Secondary End Point: | prostaticspecific antigen (PSA) changes and time to progression biochemically and radiographically. Correlative studies included prospective assessment of quality of life (QoL). |
| Patients Number: | 21 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Two patients had a partial response (PR) and eight had SD. The OR was 13% (2/15) . 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. |
| Disease Control Rate: | the overall clinical benefit (OR+SD) was 67% (10/15) |
| Median Time to Progression: | Median time to radiographic disease progression was 2 months (range 210 months). Median time to progression by PSA was 2 months (range 110 months). |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | Median overall survival (OS) was 13 months (range: 237) and three patients remain alive at the data cutoff (5/2013) for an OS of 14% at 4 years on an intenttotreat analysis. |
| Adverse Event(agent arm): | Major nonhaematologic 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. |
| Conclusions: | Temsirolimus monotherapy has minimal activity in chemotherapynaive CRPC. |