A phase II trial of an adenovirus/PSA vaccine for prostate cancer.

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Author(s): R. Amato, J. Hernandez-McClain, R. Harrop, P. Cen, G. Doshi; University of Texas Medical School, Houston, TX; Oxford BioMedica, Oxford, United Kingdom



Background: The attenuated vaccinia virus (MVA) has been engineered to deliver the tumor antigen 5T4 (TroVax). More than 90% of RCCs overexpress the 5T4 antigen. A series of clinical trials were conducted to evaluate the effectiveness of MVA 5T4 as a single agent or in combination with either IL-2 or IFN.

Methods: Eligibility: Pathologic diagnosis of clear cell or papillary RCC, progressive measurable metastases, any prior therapy, adequate physiological parameters, Karnofsky performance status ? 80%, and no active CNS involvement. A regimen of MVA 5T4 alone or in combination with IL-2 or IFN was given.

Results: A total of 53 pts received MVA 5T4 alone or in combination with IL-2 or IFN. 13 pts received MVA 5T4 alone, 25 pts received low dose subcutaneous IL-2, and 15 pts received IFN. Clinical responses were assessed by measuring changes in tumor burden via computed tomography or magnetic resonance imaging scan. 5T4-specific cellular and humoral responses were monitored throughout the study. 5T4 was well tolerated with no serious adverse events attributed to vaccination. Of 48 intention-to-treat pts, 43 mounted 5T4-specific antibody responses. 2 pts showed a complete response for > 36 months and 2 other pts had a partial response for > 24 months and 12 months respectively. 20 pts demonstrated disease stabilization for ? 3 months. Median progression-free survival and overall survival for all pts was 3.6 months (range 0.8-29.7) and 13.2 months (range 1-38) respectively. A significant relationship was detected between the magnitude of 5T4-specific antibody response and overall survival.


Conclusions: 5T4, whether administered alone or in combination, was well tolerated. High frequency of 5T4-specific immune responses and associated enhanced patient survival is encouraging and warrants further investigation.