Entry Detail
| General information | |
| Database: | DB00045 |
| Objective: | To determine the potential efficacy of targeting both the tumor and bone microenvironment in patients with castrationresistant prostate cancer (PC), the authors conducted a phase 12 trial combining docetaxel with dasatinib, an oral SRC inhibitor. |
| Authors: | Araujo JC, et al |
| Title: | Dasatinib combined with docetaxel for castrationresistant prostate cancer: results from a phase 12 study. |
| Journal: | cancer |
| Year: | 2012 |
| PMID: | 21976132 |
| Trial Design | |
| Clinical Trial Id: | NCT00439270 |
| Agent: | dasatinib |
| Target: | Protooncogene tyrosineprotein kinase SRC Abl Protooncogene tyrosineprotein kinase LCK Protooncogene tyrosineprotein kinase Fyn |
| Cancer Type: | prostate cancer |
| Cancer Subtype: | advanced prostate cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | docetaxel + dasatinib |
| Study Type: | an openlabelphase I/II study |
| Key Patients Feature: | Men aged more than and equal to 18 years were eligible if they had metastatic prostate cancer that had progressed despite castrate levels of serum testosterone (less than and equal to 50 ng/dL). |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Inphase 1, 16 men received dasatinib 50 to 120 mg once daily and docetaxel 60 to 75 mg/m(2) every 21 days. Inphase 2, 30 additional men received dasatinib 100 mg once daily/docetaxel 75 mg/m(2) every 21 days. |
| Primary End Point: | Efficacy endpoints included changes in prostatespecific antigen (PSA), measurable disease, bone scans, and markers of bone metabolism. Safety and pharmacokinetics were also studied. |
| Secondary End Point: | NA |
| Patients Number: | 46 |
| Trial Results | |
| DLT_MTD: | Drugdrug interactions and a maximum tolerated dose were not identified. |
| Objective Response Rate: | Durable 50% PSA declines occurred in 26 of 46 patients (57%). Of 30 patients with measurable disease, 18 (60%) had a partial response. Fourteen patients (30%) had disappearance of a lesion on bone scan. In bone marker assessments, 33 of 38 (87%) and 26 of 34 (76%) had decreases in urinary Ntelopeptide or bonespecific alkaline phosphatase levels, respectively. |
| Disease Control Rate: | Twentyeight patients (61%) received singleagent dasatinib after docetaxel discontinuation and had stabilization of disease for an additional 1 to 12 months. |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Combination dasatinib and docetaxel therapy was generally well tolerated. Thirteen of 46 patients (28%) had a grade 34 toxicity. |
| Conclusions: | The high objective response rate and favorable toxicity profile are promising and justify randomized studies of docetaxel and dasatinib in castrationresistant PC. Parallel declines in levels of PSA and bone markers are consistent with cotargeting of epithelial and bone compartments of the cancer. Treatment with singleagent dasatinib following docetaxel cessation warrants further study. |