Related Experiment Video
Updated: Jul 31, 2025
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Flutamide With or Without PROSTVAC in Non-metastatic Castration Resistant (M0) Prostate Cancer
Ravi A Madan1, Marijo Bilusic1, Mark N Stein2
1National Cancer Institute, Bethesda, MD, USA.
Background:
Before 2018, there was no standard of care for non-metastatic (M0) castration resistant prostate cancer nmCRPC. Androgen receptor antagonists (ARAs) were commonly used sequentially nmCRPC.
Methods:
This was a multicenter, randomized clinical trial comparing the ARA flutamide+/-PROSTVAC, a pox viral vaccine targeting PSA that includes T-cell co-stimulatory molecules. Eligible men had negative CT and Tc99 bone scans, and rising PSA on ADT. Previous treatment with ARA was a stratification factor. Patients were also evaluated for antigen-specific immune responses using intracellular cytokine staining.
Results:
Thirty-three patients randomized to flutamide and 31 to flutamide+vaccine. The median age was 71.8 and 69.8 years, respectively. The median time to treatment failure after a median potential follow-up of 46.7 months was, 4.5 months (range 2-70) for flutamide alone vs. 6.9 months (2.5-40; P = .38) with flutamide+vaccine. Seven patients in each arm had a >50% PSA response. Antigen-specific responses were similar in both arms (58% of patients in flutamide alone and 56% in flutamide+vaccine). The treatments were well tolerated. The most common side effect > grade 2 was injection site reaction seen in 29/31 vaccine patients which were self-limiting.
Conclusion:
The combination of flutamide+PROSTVAC did not improve outcomes in men with nmCRPC compared with flutamide alone. (ClinicalTrials.gov Identifier: NCT00450463).
Insights
Adding the PROSTVAC vaccine to flutamide did not improve treatment outcomes for men with non-metastatic castration-resistant prostate cancer (nmCRPC). This clinical trial found no significant difference in time to treatment failure between the two groups. Prostate cancer research continues to seek effective nmCRPC therapies.
Area of Science:
- Oncology
- Immunology
- Prostate Cancer Research
Background:
- Prior to 2018, non-metastatic castration-resistant prostate cancer (nmCRPC) lacked a standard treatment protocol.
- Androgen receptor antagonists (ARAs) were often administered sequentially for nmCRPC management.
Purpose of the Study:
- To evaluate the efficacy of combining the androgen receptor antagonist flutamide with PROSTVAC, a pox viral vaccine targeting prostate-specific antigen (PSA).
- To compare treatment outcomes in patients with nmCRPC receiving flutamide alone versus flutamide plus PROSTVAC.
Main Methods:
- A multicenter, randomized clinical trial was conducted.
- Patients with non-metastatic prostate cancer and rising PSA on androgen deprivation therapy were randomized.
- Treatment arms included flutamide alone and flutamide plus PROSTVAC, with evaluation of antigen-specific immune responses.
Main Results:
- No significant difference in median time to treatment failure was observed between the flutamide alone arm (4.5 months) and the flutamide+PROSTVAC arm (6.9 months; P = .38).
- PSA response rates (>50% reduction) were similar in both groups (7 patients each).
- Antigen-specific immune responses were comparable between arms, and treatments were generally well-tolerated, with injection site reactions being the most common side effect in the vaccine group.
Conclusions:
- The combination of flutamide and PROSTVAC did not demonstrate improved outcomes for men with nmCRPC compared to flutamide monotherapy.
- The study suggests that this specific vaccine combination does not offer a clinical benefit in this patient population.
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