Outcomes of men with HIV and germ cell cancer: Results from an international collaborative study.

BACKGROUND: Previous studies have shown that men with HIV and germ cell cancer (HIV-GCC) have inferior overall survival (OS) in comparison with their HIV-negative counterparts. However, little information is available on treatments and outcomes of HIV-GCC in the era of combination antiretroviral therapy (cART). METHODS: This study examined men living with HIV who were 18 years old or older and had a diagnosis of histologically proven germ cell cancer (GCC). The primary outcomes were OS and progression-free survival (PFS). RESULTS: Data for 89 men with a total of 92 HIV-GCCs (2 synchronous GCCs and 1 metachronous bilateral GCC) were analyzed; among them were 64 seminomas (70%) and 28 nonseminomas (30%). The median age was 36 years, the median CD4 T-cell count at GCC diagnosis was 420 cells/µL, and 77% of the patients on cART had an HIV RNA load < 500 copies/mL. Stage I disease was found in 44 of 79 gonadal GCCs (56%). Among 45 cases with primary disseminated GCC, 78%, 18%, and 4% were assigned to the good-, intermediate-, and poor-prognosis groups, respectively, of the International Germ Cell Cancer Collaborative Group. Relapses occurred in 14 patients. Overall, 12 of 89 patients (13%) died. The causes of death were refractory GCC (n = 5), an AIDS-defining illness (n = 3), and other causes (n = 4). After a median follow-up of 6.5 years, the 5- and 10-year PFS rates were 81% and 73%, respectively, and the 5- and 10-year OS rates were 91% and 85%, respectively. CONCLUSIONS: The 5- and 10-year PFS and OS rates of men with HIV-GCC were similar to those reported for men with HIV-negative GCC. Patients with HIV-GCC should be managed identically to HIV-negative patients. LAY SUMMARY: Men living with HIV are at increased risk for germ cell cancer (GCC). Previous studies have shown that the survival of men with HIV-associated germ cell cancer (HIV-GCC) is poorer than the survival of their HIV-negative counterparts. This study examined the characteristics, treatments, and outcomes of 89 men with HIV-GCC in the era of effective combination antiretroviral therapies. The long-term outcomes of men with HIV-GCC were similar to those reported for men with HIV-negative GCC. Patients with HIV-GCC should be managed identically to HIV-negative patients.

A phase II trial of first-line sorafenib in patients with metastatic renal cell carcinoma unwilling to receive or with early intolerance to immunotherapy: SOGUG Study 06-01.

AIMS: Our aim was to evaluate first-line treatment of metastatic renal cell carcinoma (mRCC) with sorafenib in patients unwilling to receive immunotherapy or with early intolerance to immunotherapy. PATIENTS AND METHODS: Patients had clear-cell mRCC with good or intermediate risk status, were unsuited to cytokine therapy due to preference or intolerance (based on <4 weeks prior immunotherapy) and had not received antiangiogenic agents. Patients received sorafenib 400 mg twice daily until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). RESULTS: Twenty-six evaluable patients were enrolled at six centres between March and July 2006. The most common metastatic sites were lung and bone; nine patients had one or two metastatic lesions. Median PFS was 7.5 months (95% confidence interval [CI] 5.1-17.5) and overall survival (OS) 15.4 months (95% CI 12.9-17.4). Among 21 patients evaluable for response, 19 (90.5%) experienced disease control (including one complete response; four partial responses; 14 stable disease). The majority of adverse events were grade 1-2 (87.3%). The most common were asthenia (53.0%) and diarrhoea (50.0%). CONCLUSION: In patients with mRCC who were unwilling to receive or intolerant to immunotherapy, treatment with sorafenib led to a high rate of disease control with toxicities that were generally mild and manageable. The PFS achieved in this essentially treatment-naïve population compares favourably with that obtained in the randomised first-line phase II study.

Neoadjuvant temsirolimus effectiveness in downstaging advanced non-clear cell renal cell carcinoma.

A 35-year-old woman presented with a 12-cm right renal mass with retroperitoneal lymph node involvement and pulmonary and bone metastases. Renal mass biopsy revealed an unclassified high-grade non-clear cell renal cell carcinoma (RCC) with eosinophilic cells. Due to the extent of the disease, neoadjuvant temsirolimus was initiated. After 6 wk of treatment, a significant downstaging of the disease and complete disappearance of the metastases were noticed on computed tomography scan. Three months later, a laparoscopic radical nephrectomy and lymphadenectomy was performed. Final pathology confirmed a high-grade non-clear cell RCC, with necrotic changes on lymph node specimens, pT1bN0Mx.

A phase II study of vinorelbine and estramustine in patients with hormone-resistant prostate cancer.

INTRODUCTION: This phase II study was designed to evaluate the efficacy of vinorelbine in combination with estramustine in patients with chemotherapy-naïve hormone-refractory prostate cancer. MATERIAL AND METHODS: Patients received vinorelbine (i.v. 25 mg/m2) on days 1 and 8 every 3 weeks and estramustine (oral, 600 mg/m2) daily. Eligible patients were required to have progressive metastatic disease following the first hormonal manipulation. RESULTS: Of the 51 patients enrolled (median age = 69 years), 84% presented bone involvement and 75% had at least two organs involved at the time of study entry and 47 were evaluable for treatment efficacy. Prostate specific antigen (PSA) response (> or =50% decrease) which was the primary efficacy criterion was reported in 21 patients (41.2%) in the intent-to-treat (ITT) population and in 20 patients (48.8%) in the per protocol (PP) population. Of the 7 patients with measurable disease, 2 achieved partial response. Median progression-free survival and overall survival were 4.7 months (range: 1.9-8.6) and 14.3 months (range: 4.2-21.2), respectively. Grade 3-4 neutropenia was reported in 6.1% of patients and in 1% of cycles. The incidence of complicated neutropenia (febrile neutropenia reported in 1 patient and septic shock with severe neutropenia reported in 2 patients) was 5.8%. The most frequent grade 3-4 non-haematological events (% of patients > or =5%) included anorexia (10%), thrombosis/embolism (8%), vomiting and hypotension (6% each). There were 3 toxic deaths (5.9 %) resulting from pulmonary embolism, angina pectoris, and septic shock. The impact of combined chemotherapy on the quality-of-life (QL) of the patients was assessed between baseline and the first evaluation scheduled at 6 weeks indicated a marked reduction in pain while the rest of the symptoms remained stable. Overall, health status improved slightly over the treatment period. CONCLUSIONS: This study confirmed that the combination of vinorelbine and estramustine is an active regimen in patients with hormone-resistant prostate cancer who had not been treated previously with chemotherapy. Main toxicities included complicated neutropenia even though the incidence of severe neutropenia was low. We observed a higher incidence of toxic deaths which could have been related to the regimen of estramustine used in the study.

A phase II study of vinorelbine and estramustine in patients with hormone-resistant prostate cancer

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Introduction. This phase II study was designed to evaluate the efficacy of vinorelbine in combination with estramustine in patients with chemotherapy- naïve hormone-refractory prostate cancer. Material and methods. Patients received vinorelbine (i.v. 25 mg/m2) on days 1 and 8 every 3 weeks and estramustine (oral, 600 mg/m2) daily. Eligible patients were required to have progressive metastatic disease following the first hormonal manipulation. Results. Of the 51 patients enrolled (median age = 69 years), 84% presented bone involvement and 75% had at least two organs involved at the time of study entry and 47 were evaluable for treatment efficacy. Prostate specific antigen (PSA) response (≥50% decrease) which was the primary efficacy criterion was reported in 21 patients (41.2%) in the intent- to-treat (ITT) population and in 20 patients (48.8%) in the per protocol (PP) population. Of the 7 patients with measurable disease, 2 achieved partial response. Median progression-free survival and overall survival were 4.7 months (range: 1.9-8.6) and 14.3 months (range: 4.2-21.2), respectively. Grade 3-4 neutropenia was reported in 6.1% of patients and in 1% of cycles. The incidence of complicated neutropenia (febrile neutropenia reported in 1 patient and septic shock with severe neutropenia reported in 2 patients) was 5.8%. The most frequent grade 3-4 non-haematological events (% of patients ≥5%) included anorexia (10%), thrombosis/embolism (8%), vomiting and hypotension (6% each). There were 3 toxic deaths (5.9 %) resulting from pulmonary embolism, angina pectoris, and septic shock. The imimpact of combined chemotherapy on the quality-oflife (QL) of the patients was assessed between baseline and the first evaluation scheduled at 6 weeks indicated a marked reduction in pain while the rest of the symptoms remained stable. Overall, health status improved slightly over the treatment period. Conclusions. This study confirmed that the combination of vinorelbine and estramustine is an active regimen in patients with hormone-resistant prostate cancer who had not been treated previously with chemotherapy. Main toxicities included complicated neutropenia even though the incidence of severe neutropenia was low. We observed a higher incidence of toxic deaths which could have been related to the regimen of estramustine used in the study

Decisión terapéutica en tumores de células germinales testiculares avanzados / Therapeutic decision in advanced germ cell testicular tumors

OBJETIVO: Revisar el papel de las clasificaciones de grupos de riesgo, realizadas por Centros o Grupos Cooperativos de gran prestigio, que han tenido repercusión en el conocimiento y manejo terapeútico del TCG en todo el mundo. Asimismo se revisan los estudios publicados en la literatura en los últimos 15 años, que han proporcionado la evidencia para determinar los esquemas terapeúticos óptimos en cada subgrupo de riesgo. MÉTODO: Los pacientes con enfermedad avanzada pueden dividirse en dos o tres grupos (bajo y alto ó bajo, intermedio y alto riesgo) con diferente probabilidad de curación tras esquemas de tratamiento basados en cisplatino, clasificándose según la localización del tumor primario, la extensión de la enfermedad y los niveles de marcadores séricos. El tratamiento estándar de la enfermedad avanzada consiste en quimioterapia (QT) de primera línea con cisplatino, etopósido y bleomicina (BEP) seguido de cirugía en los casos con enfermedad residual RESULTADOS: Alrededor de un 10 por ciento de los pacientes con factores de buen pronóstico y un 30-50 por ciento con factores de mal pronóstico no serán curados tras la QT de primera línea, siendo posible rescatar a algunos de ellos con esquemas de segunda línea. La búsqueda de regímenes más eficaces en pacientes de alto riesgo, así como de regímenes menos tóxicos en los de bajo riesgo se ha visto entorpecida por la falta de consenso entre los grupos de trabajo sobre los criterios de clasificación de los pacientes en estos subgrupos pronóstico. La reciente aparición de una clasificación de consenso internacional posibilitará que los ensayos en pacientes de riesgo contengan grupos homogéneos de enfermos con el fin de obtener resultados fiables y reproducibles en distintas poblaciones CONCLUSIONES: Los tumores de células germinales (TCG) representan el paradigma de los tumores curables del adulto. Los pacientes con estadíos iniciales (I) presentan un excelente pronóstico con una probabilidad de curación >98 por ciento y han sido ampliamente revisados en otros capítulos de esta monografía. El pronóstico de los estadíos avanzados sigue siendo mejor que el de cualquiera de los tumores sólidos con similar volumen tumoral debido a la exquisita quimiosensibilidad que presentan (AU)

Quimioterapia de rescate en tumores de células germinales testiculares / Salvage chemotherapy for gem cell testicular tumors

OBJETIVO: En esta revisión se analizan las diversas opciones terapéuticas de rescate según los factores pronóstico de respuesta a las distintas alternativas terapéuticas según la situación clínica. MÉTODO: Se describen cronológicamente los esquemas de quimioterapia de rescate clásicos así como el papel de la cirugía y las nuevas drogas y modalidades terapéuticas, especialmente la intensificación con quimioterapia a dosis altas en tercera y segunda línea de tratamiento. RESULTADOS/CONCLUSIONES: Los tumores germinales testiculares representan el paradigma de los tumores curables del adulto. Mientras que la curación de los tumores en estadio I es casi universal (>98 por ciento), los pacientes con tumores avanzados presentan una tasa de curación inferior.Un 10 por ciento de los pacientes con factores de buen pronóstico y un 30-50 por ciento con factores de pobre pronóstico presentarán progresión o recurrencia de la enfermedad tras la quimioterapia de primera línea basada en una combinación de cisplatino. Los pacientes que presentan una recidiva tras la primera línea de quimioterapia tienen una probabilidad del 40 por ciento de alcanzar una segunda remisión completa con la terapia de segunda línea, pero sólo en el 20 por ciento de los pacientes será duradera, excepto en los raros casos de seminoma puro avanzado recidivado, en los cuales las perspectivas de curación con una segunda línea de quimioterapia suben al 55 por ciento. En la actualidad se dispone de nuevas estrategias incorporando nuevos fármacos como los taxanos o bien intensificando las dosis de fármacos conocidos -la quimioterapia a dosis altas- con rescate hematológico autólogo, que se han utilizado con éxito en pacientes con tumores germinales refractarios. En un análisis global de las series de enfermos tratados con quimioterapia a dosis altas en la tercera línea se observa una tasa de remisiones completas mantenidas del 22 por ciento. Sin embargo, este porcentaje se puede elevar hasta el 50 por ciento para los pacientes sin factores adversos (AU)