WT1 peptide immunotherapy for gynecologic malignancies resistant to conventional therapies: a phase II trial

The aim of the present study was to analyze the long-term survival effects of WT1 peptide vaccine, in addition to its anti-tumor effects and toxicity.

A phase II clinical trial was conducted during the period of 2004-2010 at Osaka University Hospital, Osaka, Japan. The patients who had gynecologic malignancies progressing against previous treatments received WT1 peptide vaccine intradermally at 1-week intervals for 12 weeks. The vaccination was allowed to further continue, unless the patient's condition became significantly worse due to the disease progression.

Forty out of 42 patients, who met all the inclusion criteria, underwent WT1 peptide vaccine. Among these 40 patients, stable disease was observed in 16 cases (40 %). Skin toxicity of a grade 1, 2 and 3 occurred in 25 cases (63 %), 9 cases (23 %) and a single case (3 %), respectively, and liver toxicity of grade 1 in a single case (3 %). The overall survival period was significantly longer in cases positive for the WT1 peptide-specific delayed-type hypersensitivity (DTH) reaction after the vaccination, compared to those negative for the DTH reaction (p = 0.023). Multivariate Cox proportional hazards analysis demonstrated that the adjusted hazard ratio for the negative DTH reaction was 2.73 (95 % CI 1.04-7.19, p = 0.043).

WT1 peptide vaccine may be a potential treatment, with limited toxicity, for gynecologic malignancies that have become resistant to conventional therapies. Larger scale of clinical studies is required to establish the efficacy of the WT1 peptide vaccine for gynecologic malignancies.