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Updated: Aug 17, 2025
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Biomarker Development Trial of Satraplatin in Patients with Metastatic Castration-Resistant Prostate Cancer
Bobby C Liaw1, Che-Kai Tsao1, Sonia Seng1
1Division of Hematology and Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Background:
In the phase III SPARC trial, satraplatin, an oral platinum analogue, demonstrated anticancer activity in men with metastatic castration-resistant prostate cancer (mCRPC). Repeat biopsies are uncommon in mCRPC, limiting the feasibility of tissue-based biomarkers. This phase II study sought to evaluate the feasibility and utility of blood-based biomarkers to identify platinum-sensitive mCRPC.
Methods:
Patients with mCRPC who had progressed on docetaxel were enrolled at a single center from 2011 to 2013. Subjects received satraplatin 80 mg/m2 by mouth daily on days 1-5 and prednisone 5 mg PO twice daily, on a 35-day cycle. Serial peripheral blood samples were collected for biomarker assessment.
Results:
Thirteen docetaxel-refractory mCRPC patients were enrolled, with a median age of 69 years (range 54-77 years) and median PSA of 71.7 ng/mL (range 0.04-3057). Four of 13 patients (31%) responded to satraplatin (defined as a PSA decline of ≥30%). Responders demonstrated improved time to disease progression (206 vs. 35 days, HR 0.26, 95% CI, 0.02-0.24, P = .003). A 6-gene peripheral blood RNA signature and serum tissue inhibitor of metalloproteinase-1 (TIMP-1) levels were assessed as biomarkers, but neither was significantly associated with response to satraplatin.
Conclusion:
In this small series, one-third of mCRPC patients responded to platinum-based chemotherapy. Peripheral blood biomarker measurement is feasible in mCRPC, though the biomarkers we investigated were not associated with platinum response. Other biomarkers, such as DNA damage repair mutations, should be evaluated.
Insights
This study found that one-third of men with metastatic castration-resistant prostate cancer (mCRPC) responded to satraplatin chemotherapy. While blood biomarkers are feasible, the ones tested did not predict response to platinum therapy.
Area of Science:
- Oncology
- Translational Research
- Biomarker Discovery
Background:
- Metastatic castration-resistant prostate cancer (mCRPC) presents challenges for biomarker identification due to infrequent repeat biopsies.
- Satraplatin, an oral platinum analogue, showed anticancer activity in mCRPC patients.
- There is a need for feasible, blood-based biomarkers to predict platinum sensitivity in mCRPC.
Purpose of the Study:
- To evaluate the feasibility and utility of blood-based biomarkers for identifying platinum-sensitive mCRPC.
- To assess patient response to satraplatin in docetaxel-refractory mCRPC.
Main Methods:
- A phase II study enrolled 13 docetaxel-refractory mCRPC patients.
- Patients received oral satraplatin and prednisone over 35-day cycles.
- Peripheral blood samples were collected for biomarker analysis, including a 6-gene RNA signature and serum TIMP-1 levels.
Main Results:
- Four out of 13 patients (31%) responded to satraplatin, defined by a PSA decline of ≥30%.
- Responders showed significantly improved time to disease progression compared to non-responders.
- Neither the 6-gene RNA signature nor serum TIMP-1 levels were significantly associated with satraplatin response.
Conclusions:
- Approximately one-third of mCRPC patients responded to platinum-based chemotherapy.
- Peripheral blood biomarker measurement is feasible in mCRPC.
- The investigated blood biomarkers were not associated with platinum response, suggesting the need to explore other biomarkers like DNA damage repair mutations.
