Entry Detail
| General information | |
| Database: | DB00210 |
| Objective: | One of the central unanswered questions in prostate cancer research is the significance of tyrosine kinase inhibitor (TKI)induced improvements in (99m)Tcmethylene diphosphonate ((99m)TcMDP) bone scans. Multitargeted tyrosine kinase inhibition has recently shown promise in the management of castrationresistant prostate cancer. In some cases, TKI inhibition has produced unprecedented improvements in bone metastases as detected by (99m)TcMDP bone scans. The significance of these improvements is not known. In order to gain insight about the effects of TKIs on bone scans in prostate cancer, they systematically evaluated images from a phase II study of sunitinib, a multitargeted TKI. |
| Authors: | Saylor PJ, |
| Title: | Multitargeted tyrosine kinase inhibition produces discordant changes between 99mTcMDP bone scans and other disease biomarkers: analysis of a phase II study of sunitinib for metastatic castrationresistant prostate cancer. |
| Journal: | J Nucl Med. |
| Year: | 2012 |
| PMID: | 22984218 |
| Trial Design | |
| Clinical Trial Id: | NCT00299741 |
| Agent: | sunitinib |
| Target: | FL cytokine receptor Mast/stem cell growth factor receptor Vascular endothelial growth factor receptor 2 Plateletderived growth factor receptor |
| Cancer Type: | prostate cancer |
| Cancer Subtype: | advanced castrationresistant prostate cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | an openlabelphase II study |
| Key Patients Feature: | eligible men with histologically confirmed adenocarcinoma of the prostate and evidence of progression despite castrate testosterone (serum testosterone < 50 ng/dL). |
| Biomarker: | PSA |
| Biomark Analysis: | Serum prostatespecific antigen levels were prospectively monitored as a biomarker for cancer activity. |
| Control Group Info: | single arm |
| Treatment Info: | Participants received sunitinib in 6wk cycles (50 mg daily; 4 wk on, 2 wk off). They examined baseline and 12wk bone scan images. |
| Primary End Point: | PSA response rate; |
| Secondary End Point: | an objective response rate according to the response evaluation criteria in solid tumors (RECIST). |
| Patients Number: | 34 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | Analysis at 12 wk revealed 1 partial response by the response evaluation criteria in solid tumors (RECIST) and 2 confirmed PSA responses. There were 25 subjects who underwent bone scans at both time points (baseline and week 12) and who had bone metastases detectable at baseline. Within that group of 25, they found 5 bone scan partial responses and 1 complete response. None of those 6 subjects exhibited a PSA response (more than and equal to 50% decline from baseline) or RECIST response. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | NA |
| Conclusions: | They found a relatively high rate of (99m)TcMDP bone scan response to sunitinib among men with metastatic prostate cancer. Further, they found that none of the subjects exhibiting bone scan responses experienced concordant improvements in PSA or CT evidence of disease by accepted criteria. This discordance argues that osteoblastic assessment provides an incomplete assessment of treatmentinduced changes. Rational development of multitargeted TKIs for prostate cancer requires improved understanding of treatmentinduced bone scan changes. Optimal imaging strategies may include evaluation of perfusion or direct tumor activity. |