Entry Detail
| General information | |
| Database: | DB00046 |
| Objective: | There is a need for efficacious therapies for metastatic castrationresistant prostate cancer (mCRPC) after disease progression on docetaxel. The SRC tyrosine kinase and its related family members may be important drivers of prostate cancer and can be inhibited by dasatinib. |
| Authors: | Twardowski PW, et al |
| Title: | a phase II trial of dasatinib in patients with metastatic castrationresistant prostate cancer treated previously with chemotherapy. |
| Journal: | Anticancer Drugs. |
| Year: | 2013 |
| PMID: | 23652277 |
| Trial Design | |
| Clinical Trial Id: | NA |
| Agent: | dasatinib |
| Target: | Protooncogene tyrosineprotein kinase SRC Abl Protooncogene tyrosineprotein kinase LCK Protooncogene tyrosineprotein kinase Fyn |
| Cancer Type: | prostate cancer |
| Cancer Subtype: | advanced castrationresistant prostate cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a phase II trial |
| Key Patients Feature: | patients with metastatic castrationresistant prostate cancer treated previously with chemotherapy |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | after one previous chemotherapy, pts were started with dasatinib at 70 mg twice daily, amended to 100 mg daily. |
| Primary End Point: | disease control (DC) rate, defined as complete response (CR), partial response (PR), or stable disease (SD) in prostate specific antigen (PSA), RECIST, bone scan, and FACTP score. |
| Secondary End Point: | progression free survival, toxicity, and pharmacokinetic and pharmacodynamic correlatives. |
| Patients Number: | 41 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | Dasatinib induced a decrease in phytohemagglutininstimulated CSF2, CD40L, GZMB, and IL2 mRNAs in blood cells, indicating target engagement. Decreases in plasma IL6 and bone alkaline phosphatase, and in urinary Ntelopeptide, were associated with DC. Dasatinib has definite but limited activity in advanced mCRPC |
| Disease Control Rate: | Five patients shotheyd DC after 8 weeks of therapy (18.5% DC, 95% CI: 6.338.1%). One PR (3.7% response rate, 95% CI: 0.119.0%) was observed in a patient treated for 284 days. Ttheylve patients (43%) discontinued treatment for toxicity. |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most common attributable grade 3 and 4 toxicities included fatigue (19%), hyponatremia (8%), diarrhea (8%), dyspnea (8%), gastrointestinal bleed (8%), pleural and pericardial effusions (4%), elevated lipase (4%), and anemia (4%).The most common cause of discontinuation of dasatinib was PD (54%); however, 43% of patients were taken off the protocol because of toxicities, predominantly fatigue. |
| Conclusions: | The observation of a patient with prolonged, objective, clinically significant benefit warrants molecular profiling to select the appropriate patient population. |