Randomized comparison of high-dose and low-dose intravenous interleukin-2 for the therapy of metastatic renal cell carcinoma: an interim report.

Yang, James Chih‐Hsin; Topalian, Suzanne L.; Parkinson, David; Schwartzentruber, Douglas J.; Weber, J.; Ettinghausen, Stephen E.; White, Donald E.; Steinberg, Seth M.; Cole, David J.; Kim, H I

doi:10.1200/jco.1994.12.8.1572

Cited by 162 publications

(51 citation statements)

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“…Overall response rates of renal cell cancer to IL-2 remain low (15-25%) with a complete remission rate of 5-10%. 45,46 Yet the dramatic response in a few patients where all other therapy has failed has established IL-2 as the standard therapy for this disease. Studies using IL-2 for ALL appear less encouraging.…”

Section: Resultsmentioning

confidence: 99%

Interleukin-2 and leukemia

1998

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Leukemia has been treated with chemotherapy for the past 40 years with only moderate success. A growing body of evidence suggests that by augmenting the immune system more effective results may be obtained. This is highlighted by T cell reinfusions resulting in durable remissions in patients with chronic myelogenous leukemia who have relapsed after an allogeneic transplant. Interleukin-2 is the primary growth factor for T lymphocytes and is a stimulator of natural killer cell activity. It has now been shown that a limited number of otherwise refractory leukemias can be effectively treated with interleukin-2. However, there remains a lack of correlation between the biologic and clinical effects of interleukin-2. The clinical activity of interleukin-2 appears to be greatest in myeloid leukemias. A variety of dose schedules and routes of administration make it difficult to determine if interleukin-2 given to patients in clinical remission is of benefit. Large randomized studies are necessary to explore the role of interleukin-2 in leukemia.

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Section: Resultsmentioning

confidence: 99%

Interleukin-2 and leukemia

1998

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“…Posteriormente otros estudios reuniendo un total de 256 pacientes de varios centros confirmaron los resultados de Yang 25 .…”

Section: Actas Urológicas Españolasunclassified

Tratamiento del cáncer renal metastásico: vigencia de la inmunoterapia

Ibarguren

2009

Actas Urológicas Españolas

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M ucho han variado las perspectivas terapéuti-cas aplicables al cáncer renal a lo largo de la historia. De todos es sabido y aceptado que el único tratamiento definitivo y curativo del carcinoma renal es el quirúrgico. Desde que Robson 1 describió en 1963 la nefrectomía radical en un intento de reducir la recidiva local y la progresión a distancia de la enfermedad muchos han sido los tratamientos empleados para combatirla.De todos es sabido que el carcinoma renal se diagnostica en un 30% de los casos como enfermedad avanzada. Asimismo sabemos que el 30% de los casos presumiblemente localizados desarrollará enfermedad a distancia tras el primer tratamiento quirúrgico. En conjunto, el 40% de los pacientes que sufren la enfermedad acabarán sucumbiendo a ella 2 .En 2002 ya se apuntaba la incidencia en progresión de este tipo tumoral que era de 6/100.000 habitantes/año en hombres y de 2,4/100.000/año para mujeres, con un aumento anual de 7% en hombres y de 10% en mujeres 3 . MODALIDADES TERAPÉUTICAS EN EL CÁNCER RENAL DISEMINADO ResumenObjetivo: Evaluar la importancia y efectos de la inmunoterapia clásica en el tratamiento del cáncer renal diseminado. Material y métodos. Se revisan los datos históricos de los estudios realizados con citocinas, interferon e interleukina, evaluando sus combinaciones, y comparando los diferentes estudios relevantes existentes. Comentarios: Aunque diversos, los resultados son pobres en cuanto a respuesta objetivable y en cuanto a duración de la misma, observando series ya históricas que empleando interleukina2 lograron, pesar de graves efectos secundarios, remisiones incluso completas de la enfermedad. Conclusiones: En la actualidad y tras el advenimiento de los nuevos fármacos, el empleo de la inmunoterapia clásica puede encontrar indicación en pacientes concretos, con buen estado general, con nefrectomía previa por carcinoma de células claras, al menos 12 meses antes de la aparición de metástasis en un solo órgano, preferentemente pulmón, y con niveles normales de hemoglobina, calcio y lactodehidrogenasa, buscando ese pequeño porcentaje de respuestas estables y mantenidas.Palabras clave: Inmunoterapia. Citocinas. Interferon. Interleukina. Treatment of metastatic renal cancer: current validity of immunotherapy AbstractObjective: To assess the significance and effects of conventional immunotherapy for management of disseminated renal cancer. Materials and methods:Historical data from studies conducted with cytokines, interferon, and interleukin are reviewed, their combinations are evaluated, and the different relevant studies available are compared.Discussion: While diverse, results are poor in terms of objective response and its duration. Historical series using interleukin-2 achieved, despite severe side effects, disease remissions, some of them complete. Conclusions:Currently, after the advent of new drugs, use of conventional immunotherapy may be indicated for specific patients with a good general condition undergoing previous nephrectomy for a clear cell carcinoma at least 12 month...

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“…19,20 However, a phase III study of the Cytokine Working Group found that treatment with high-dose IL-2 demonstrated a significantly higher objective response rate than did treatment with low-dose IL-2/interferon. 21 Conventional treatment options are summarized in Table 1.…”

Section: Therapy and Survivalmentioning

confidence: 99%

Nonablative hematopoietic cell transplantation for the treatment of metastatic renal cell carcinoma

Nelson

Logan

Abonour

2002

Bone Marrow Transplant

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Summary:Nonablative hematopoietic cell transplantation (HCT) is becoming a preferred treatment for those recipients in whom the potential toxicity risk of standard ablative allogeneic therapy may be unacceptable. Graft-versusmalignancy effects may be generated against epithelial malignancies which are similar to the graft-versus-leukemia activity that is well documented in human hematological malignancies. Renal Metastatic renal cell carcinomaOf the 30 000 cases of kidney cancer per year which are diagnosed in the United States, there are over 12 000 deaths. The incidence of renal cell carcinoma (RCC) has increased by 38% from 1976-1990 and occurs predominantly in persons between the ages of 50 to 70.1 Common sites of metastases include lung, soft tissue, bone, liver, skin and less commonly, the central nervous system. Some metastases initially progress slowly, if at all, while others progress rapidly, making treatment difficult. Treatment for metastatic renal cancer is not usually successful and the median prognosis for survival despite added cytokine therapy is 10 months. 5 Therapy and survivalStandard chemotherapeutic and hormonal approaches are generally unsuccessful. 6,7 Immunomodulator therapies utilizing interferon have been used with some success in patients with metastatic RCC.8-12 Nephrectomy, followed by interferon alfa-2b, accomplishes longer survival among patients with metastatic RCC than does interferon therapy alone.9 IL-2 is FDA-approved and considered standard therapy for metastatic renal cell carcinoma; however, many patients are not eligible because of poor performance status or concurrent organ dysfunction. Approximately 15-20% of patients have an objective response to therapy, and although the complete response (CR) rate is 5-7%, approximately 80% of these complete responders will experience response duration of greater than 2 years.13-16 Toxicity of high-dose IL-2 therapy is significant, although the treatment-related mortality is less than 1%.14 The toxicities include hypotension requiring pressors, major organ failure, myocardial infarction and potentially fatal systemic capillary leak. Fisher reported that the median response duration of the original cohort of 255 RCC patients treated with high-dose IL-2 was 54 months (range, 3-131 months). 17,18The median duration for complete responders was not reached, but was greater than or equal to 80 months (range, 7-131 months). Median survival for all 255 patients was 16.3 months, with 10-20% estimated to be alive 5-10 years post treatment. Regimens combining IL-2 and other agents appear to have similar response rates compared to IL-2 alone.12,15 Low-to moderate-dose parenteral IL-2 may be associated with similar response rates and less toxicity. 19,20 However, a phase III study of the Cytokine Working Group found that treatment with high-dose IL-2 demonstrated a significantly higher objective response rate than did treatment with low-dose IL-2/interferon. 21 Conventional treatment options are summarized in Table 1.

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Randomized comparison of high-dose and low-dose intravenous interleukin-2 for the therapy of metastatic renal cell carcinoma: an interim report.

Cited by 162 publications

References 13 publications

Interleukin-2 and leukemia

Interleukin-2 and leukemia

Tratamiento del cáncer renal metastásico: vigencia de la inmunoterapia

Nonablative hematopoietic cell transplantation for the treatment of metastatic renal cell carcinoma

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