RESUMEN

BACKGROUND: Novel immune therapies targeting tumor specific antigens are being developed. Our purpose was to determine expression of the cancer testes antigen NY-ESO-1 in renal cell carcinoma (RCC), as NY-ESO-1 targeting approaches, particularly adoptive cell therapy, have not been evaluated in this disease. METHODS: We employed tissue microarrays containing >300 unique RCC cases and adjacent benign renal tissue to determine NY-ESO-1 expression using a quantitative immunofluorescence method. In addition, we studied NY-ESO-1 expression in 35 matched primary and metastatic RCC specimens to assess concordance between different tumor sites. RESULTS: NY-ESO-1 was highly expressed in a subset of RCCs. Expression in primary RCC specimens was significantly higher than adjacent normal renal tissue (P<0.0001) and higher in clear cell carcinomas than papillary RCC (P<0.0001). Expression levels in metastatic specimens were higher than in matched primary samples (P=0.0018), and the correlation between the two sites was modest (χ2=3.5, p=0.06). CONCLUSIONS: Aberrant NY-ESO-1 expression seen in clear cell RCC suggests that NY-ESO-1 targeting approaches should be studied in this disease. Expression is higher in metastatic sites, and discordance between primary and metastatic sites in some patients suggests that patient selection for these therapies should be based on expression in metastatic rather than nephrectomy specimens.

Asunto(s)

Antígenos de Neoplasias/análisis , Carcinoma de Células Renales/inmunología , Neoplasias Renales/inmunología , Proteínas de la Membrana/análisis , Antígenos de Neoplasias/biosíntesis , Antígenos de Neoplasias/inmunología , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/terapia , Estudios de Cohortes , Humanos , Inmunoterapia , Neoplasias Renales/patología , Neoplasias Renales/terapia , Proteínas de la Membrana/biosíntesis , Proteínas de la Membrana/inmunología , Terapia Molecular Dirigida , Metástasis de la Neoplasia , Análisis de Matrices Tisulares

RESUMEN

BACKGROUND: Cisplatin-based therapy is associated with acute and late toxicities. Therefore, a potentially less toxic carboplatin-based regimen was evaluated in patients with advanced seminoma. PATIENTS AND METHODS: Eighteen patients with advanced seminoma were treated on outpatient basis with carboplatin (AUC5) at day 1, etoposide (100 mgm(-2)) at days 1-5, and bleomycin (30 IU) at day 2 (CEB). Treatment was 3-weekly for a total of 4 cycles. Outcome and toxicities were analyzed. RESULTS: Median follow-up was 4 years and 7.5 months. Five-year progression-free survival was 86.6% (95% confidence interval (CI), 70.6%-100%), 5-year overall survival 100%, and 10-year overall survival 85% (95% CI, 63.3%-100%); 39% of all patients reached complete remission. Two patients underwent adjuvant treatment. Two patients relapsed; 1 is in ongoing remission 4 years after salvage therapy, the other died almost 6 years after CEB-therapy, despite multiple lines of salvage therapy. The main acute toxicity observed was hematologic. No late cardiovascular events or secondary malignancies were noted. CONCLUSION: CEB treatment is effective in advanced seminoma, showing minor toxicity. Progression-free and overall survival rates at 5 and 10 years are comparable to those achieved with cisplatin-based therapy. This indicates that carboplatin-combination therapy might be a good alternative to cisplatin-based therapy in the treatment of advanced seminomas.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Terapia Recuperativa , Seminoma/tratamiento farmacológico , Neoplasias Testiculares/tratamiento farmacológico , Adulto , Bleomicina/administración & dosificación , Carboplatino/administración & dosificación , Cisplatino/administración & dosificación , Etopósido/administración & dosificación , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Pronóstico , Inducción de Remisión , Seminoma/mortalidad , Seminoma/patología , Tasa de Supervivencia , Neoplasias Testiculares/mortalidad , Neoplasias Testiculares/patología

RESUMEN

Melanoma is the leading cause of fatal skin cancer, and in the past few decades, there has been an increase in the incidence of and mortality from metastatic melanoma. Until recently, the therapeutic options for treatment of metastatic melanoma were limited. The approval of ipilimumab (an anti-CTLA-4 antibody) and vemurafenib (mutant B-RAF(V600E) kinase inhibitor) by the Federal Drug Administration has led to a new era in melanoma treatment, and additional promising drugs and drug combinations are currently being investigated. As the choices of treatment for melanoma have expanded, the need to identify predictive biomarkers to tailor treatment strategies to individual tumor or immune system characteristics has become necessary. Such strategies have the potential of maximizing antitumor effect while minimizing toxicity and improving clinical benefit. In this article, we review the currently approved targeted therapies in melanoma and discuss the future of personalized therapy for this disease.