Safety and immunogenicity exploratory analysis of the HER-1/VSSP vaccine in asymptomatic patients with metastatic prostate cancer
Abstract
Introduction: In the context of hormonal resistance in prostate cancer, patients in a good general state or asymptomatic may benefit from active immunotherapy in the time to progression.
Objective: Evaluate the safety, immunogenicity and clinical effect of the human epidermal growth factor receptor 1 (HER-1) vaccine preparation.
Methods: A preliminary report was developed for the Phase I clinical trial, randomized to two dose groups: 400 and 800 µg of extracellular domain subcutaneous vaccine (ECD- HER-1), the first five doses every 14 days (induction) and then every 28 days until one year of maintenance. A comparison was made of the variables for ten immunized asymptomatic patients with metastatic prostate cancer (p < 0.05). Adverse events were analyzed and classified. Identification was carried out of anti-HER-1 IgG antibody titers in immune serums that recognize tumor cell line A431, determining myeloid-derived suppressor cells.
Results: Mean age was 74 years (62-79), with a predominance of white skin color and Gleason score 7. A total 49 adverse events were recorded (13.6% related). Of these, 31.8% were severe or very severe and life-threatening, and none showed a causal relationship. Clinical and biochemical progression was observed in 50% of the patients after one year's follow-up. On day 112 anti-HER-1 antibody titers of 1/600 were detected in 2/10 patients. Non-recognition of immune serums to tumor cell line A431 was considered. Mean survival was not achieved.
Conclusions: Administration of the vaccine was safe, but the expected immunogenicity was not obtained. Benefit was not observed in the clinical and/or biochemical response. No significant differences were found between the dose groups.
Key words: prostate cancer; epidermal growth factor; cancer vaccine; toxicity.Downloads
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