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).
However, there have been some concerns expressed by clinicians, and more importantly by patients themselves, that the term castration implies some sort of testicular removal, which has a negative connotation for many men who have this disease.
Hormone-refractory prostate cancer and androgen-independent prostate cancer did not have this perceived stigma, but in contrast, they have proven to be considerably inaccurate, as second-generation androgen deprivation therapy clinical trials are beginning to demonstrate.
Therefore, we would like to propose that a term such as endocrine-resistant prostate cancer may be a better description to utilize with our colleagues and patients. It is both accurate and less emotionally charged. Seen in this fashion, it gives us in the field, as well as our patients, a clearer way to view therapeutic options (which will increase significantly in the years to come).
Therapeutically, if patients knew their disease was either endocrine sensitive or endocrine resistant, potentially approvable agents like Abiraterone, MDV-3100, and even estrogenic compounds could be clearly delineated from the evolving nonhormonal options that are also coming down the pike, like immunotherapy, targeted agents, and newer chemotherapies.
Kimura said that although percentage PSA decline is the same in both vaccination/dexamethasone and dexamethasone alone group, PSA-PFS was significantly longer (p<0.0008) in the vaccination group.
"This means that the anti-tumour immune response may play an important role in suppressing disease progression. This therapeutic strategy using peptide vaccines is likely to be comparable as that from currently developed anti-androgenic agents such as abiraterone acetate, MDV3100," Kimura noted.
Castration resistant prostate cancer is a difficult patient group to manage since although a number of therapeutic modalities have been developed, none have lived up to the full expectations and treatment options remain limited.
Kimura added that although the concept of immunotherapy for cancer is not new, recent technological advances have opened new avenues to explore and optimize peptide-based immunotherapy.
Provided by ArmMed Media
