A phase I study of personalized peptide vaccination for advanced urothelial carcinoma patients who failed treatment with methotrexate, vinblastine, adriamycin and cisplatin.

OBJECTIVE: • To investigate the safety and immune responses of 12 consecutive weeks of once-weekly personalized peptide vaccine (PPV) administration in patients with advanced urothelial carcinoma (UC) for whom therapy with methotrexate, vinblastine, adriamycin and cisplatin (MVAC) has failed.

PATIENTS AND METHODS: • A phase I trial was designed. Ten patients with MVAC-refractory advanced or metastatic UC were treated with weekly personalized peptide vaccine 12 times using positive peptides chosen from 14 and 16 peptides in patients with human leucocyte antigens A24 and A2, respectively. • Peptide-specific cytotoxic T lymphocyte precursor analysis by interferon-γ production and peptide-reactive immunoglobulin G (IgG) using an enzyme-linked immunosorbent assay was monitored during the treatment.

RESULTS: • The peptide vaccination was safe and well tolerated with no major adverse effects. Increased cytotoxic T lymphocyte response and the anti-peptide IgG titre were revealed by the post-vaccination sera in eight patients. • Clinical responses were as follows: one complete response, one partial response, two stable disease and six progressive disease. • Median progression-free survival and overall survival were 3.0 and 8.9 months, respectively. In the four responders, median progression-free survival and overall survival were 21 and 24 months, respectively.

CONCLUSIONS: • This phase I study showed the safety of and boosted immune responses in response to PPV for advanced UC. • The potential efficacy of 12 consecutive weekly vaccinations with PPV in patients with advanced UC merits further investigation based on these findings.