Vaccine and corticosteroid combination shows promise in castration-resistant prostate cancer

Multipeptide vaccination therapy combined with the low-dose corticosteroid drug dexamethasone shows promise in treating chemotherapy-naïve castration-resistant prostate cancer (CRPC). A recent study showed the promising benefit of this combination therapy in patients who are chemotherapy-naïve or those not yet exposed to specific antigens.

"Results of our randomized prospective study suggest that multipeptide 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 Takahiro Kimura, MD, of the Department of Urology of Jikei University School of Medicine in Tokyo, Japan.

Since immunotherapy does not have a strong ability to decrease tumor 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 major histocompatibility complex 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.

Patients with early stage CRPC (PSA <10 ng/ml) were randomized to two treatment groups: peptide vaccine with low dose (1 mg/day) dexamethasone, or low dose dexamethasone alone. The patients were vaccinated subcutaneously with 3 mg of selected peptides (maximum of four kinds) 6 times at 2-week intervals. Dexamethasone 1 mg/day orally was started on the first day of peptide vaccination. Toxicity assessment, immunologic responses, and clinical responses were investigated every 3 months. The primary end point of the study is progression-free survival including serum prostate-specific antigen (PSA).

Kimura said that although percentage PSA decline is the same in both vaccination/dexamethasone and dexamethasone alone groups, PSA-progression-free survival (PFS) was significantly longer (P <.0008) in the vaccination group.

"This means that the antitumor 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 antiandrogenic agents such as abiraterone acetate, MDV3100," Kimura noted.

Castration-resistant prostate cancer is a difficult disease to manage. Although a number of therapeutic modalities have been developed, none have lived up to their potential efficacy, 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.

"Since the antitumor effects of peptide vaccination are driven by different mechanisms as those from ADT and chemotherapy, we may circumvent many of the pitfalls experienced with the current therapies. We believe that this treatment approach will be key in order to achieve a breakthrough as a new therapeutic option for CRPC," he said.

This study won third prize for best abstract at the 28th European Association of Urology Congress, which was held in Milan, Italy, March 15-19, 2013.

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