Japanese P2 study shows potential of combined vaccine and steroid drug in castration-resistant PCa

Multi-peptide vaccination therapy combined with the low-dose steroid drug dexamethasone shows promise in treating chemotherapy-naive castration resistant prostate cancer (CRPC) patients.

The study, which won the third prize for best abstract in oncology at the 28th European Association of Urology Congress held in Milan, Italy from 15 to 19 March, showed the promising benefit of this combination therapy in patients who are chemotherapy-naive or those not yet exposed to specific antigens.

"Results of our randomized prospective study suggest that multi-peptide vaccination therapy in combination with low dose dexamethasone has the therapeutic potential as a safe and efficient option for chemotherapy-naïve CRPC patients," said lead study author Dr. Takahiro Kimura, of the Jikei University School of Medicine, Dept. of Urology, Tokyo, Japan.

Since immunotherapy does not have a strong ability to decrease tumour burden, it is considerably difficult to evaluate the full extent of a significant therapeutic effect with peptide vaccines, explained Kimura. "Taking this into consideration, the present evidence is promising," he said.

The researchers have previously developed MHC class-I restricted peptide vaccines for prostate cancer and carried out a phase 1 trial to assess safety and immunological evaluation. In the present study, Kimura and his colleagues conducted a randomized phase 2 study to evaluate the efficacy of peptide vaccine therapy for chemotherapy naïve CRPC patients.

Early stage CRPC (PSA<10ng/ml) patients were randomized to two treatment groups; peptide vaccine with low dose (1mg/day) dexamethasone (Dx), while the other group were given low dose Dx alone. The patients were vaccinated subcutaneously with 3 mg of selected peptides (max. 4 kinds) six times at two weeks interval. Dx 1mg/day p.o. was started on the first day of peptide vaccination. Toxicity assessment, immunological and clinical responses were investigated every three months. The primary endpoint of the study is progression-free survival including serum PSA.

The euphemistic term castration-resistant prostate cancer (CRPC) has slowly entered the everyday lexicon of those who study and treat prostate cancer. Ahmann and Crawford utilized this term in 1987. Emanating from what used to be called hormone-refractory prostate cancer and/or androgen-independent prostate cancer, this CRPC consensus definition was first formally reintroduced at a 2005 ODAC discussion on prostate cancer trial end points. Subsequently, in 2008, it was specifically defined in a Prostate Cancer Working Group Guidelines report, published in Journal of Clinical Oncology.

At that time, Scher et al recognized that despite medical or surgical castration, prostate cancers were still sensitive to subcastrate levels of androgens, either emanating from the adrenal cortex or from prostate cancer cells themselves (with direct intracrine activation of the androgen receptor cascade).