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Bioquimioterapia ambulatoria con cisplatino, dacarbacina, interleucina-2 e interferón-alfa en pacientes con melanoma avanzado. Estudio multicéntrico en 44 pacientes

Ambulatory biochemotherapy with cisplatin, dacarbazine, interleukin-2 and interferon alpha in patients with advanced melanoma. A 44-patient multicenter study

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Resumen

Fundamento

Se ha descrito una importante actividad (50% de respuestas objetivas) con un pequeño número de supervivientes en los ensayos clínicos de quimioinmunoterapia (QIT) para el melanoma diseminado. En la mayoría, la hospitalización era un requerimiento habitual.

Objetivos

Valorar la posibilidad de administración ambulatoria completa de la QIT dentro de un ensayo fase II multicéntrico con cisplatino+dacarbacina (DTIC) en un día, combinado con la administración subcutánea de interleucina-2+interferón-α en pacientes con melanoma metastásico.

Pacientes y métodos

Los ciclos, administrados cada 21 días, incluían cisplatino 80 mg/m2 y DTIC 800 mg/m2 intravenosos el día 1, con inyecciones subcutáneas de interleucina-2 9 millones UI/m2 del día 2 al 5 e interferón-a 5 millones IU/m2 del día 1 al 5. No se permitió la utilización de corticoides, salvo los 20 mg de dexametasona previo al cisplatino del día 1 como antiemético. Tras 6 ciclos, los pacientes sin progresión recibieron otros 6 ciclos de inmunoterapia sola.

Resultados

Se han tratado 44 pacientes con melanoma metastásico. Hombres/mujeres: 30/14. Edad mediana: 47. Mediana de estado funcional (ECOG): 0 (0–2). Se han administrado 224 ciclos completos. La toxicidad fue aceptable: la toxicidad grado 3 incluyó náuseas (6% de los ciclos), vómitos (10%), fiebre (1%), neutropenia (1%), anemia (0,8%), astenia (2%), elevación de las transaminasas (0,8%) y elevación de la creatinina sérica (0,8%). La respuesta (39 pacientes evaluables después de tres o más ciclos, resto demasiado pronto): respuesta completa 4 pacientes (10,2 %), respuesta parcial 13 (33,3%); enfermedad estable 8 (20,5%), progresión 14 p (35,8%). Tras una mediana de seguimiento de 20 meses o hasta la muerte, la mediana de la supervivencia fue de 11,6 meses.

Conclusiones

La actividad y limitada toxicidad de este régimen permite su uso ambulatorio. La superioridad de la QIT sobre cada una de las modalidades de tratamiento aisladas todavía ha de ser confirmada.

Abstract

Background

Significant activity (50% objective responses) plus a small fraction of long term survivors have been reported in pilot trials of chemoinmunotherapy (CT-IT) for disseminated melanoma. Requirement for hospitalization is a major inconvenience.

Aims

To assess the feasibility of fully ambulatory CT-IT with single-day cisplatine+dacarbacine (DTIC) combined with subcutaneous interleukin-2+interferon-a for patients (p) with metastatic melanoma in a multicenter phase II trial.

Patients and methods

Courses, to be repeated every 21 days, included cisplatin 80 mg/m2 and DTIC 800 mg/m2, both iv on day 1, plus subcutaneous injections of interleukin-2 9 million/m2 IU, day 2 to 5 and interferon-a 5 million m2 IU day 1 to 5. No corticosteroids were allowed except for 20 mg dexamethasone before cisplatine on day 1 for antiemesis. After 6 courses p without progression received 6 additional courses of IT alone.

Results

44 p with metastasic melanoma have been treated. Male/female: 30/14. Median age: 47 years. Performance status (ECOG): 1 (0–2). Full doses of therapy have been delivered in 224 courses. Toxicity was acceptable: grade 3 toxicity included nausea (6% of courses), vomiting (10%), fever (1%), neutropenia (1%), anemia (0.8%), asthenia (2%), elevation of transaminases (0.8%) and elevation of serum creatinine (0.8%). Response (39 p evaluable after 3 or more courses; rest too early): complete response 4 p (10.2%); partial response 13 p (33%); stable disease 8 p (20.5%); progression 14 p (35.8%). With median follow-up of 20 months or to death, median survival was 11.6 months.

Conclusions

The activity and limited toxicity of this regimen allow its ambulatory use. The superiority of CT-IT over each modality alone remains to be confirmed.

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Authors and Affiliations

  1. Hospital Clínico Lozano Blesa, Zaragoza

    Elena Filipovich Vegas, José Ignacio Mayordomo Cámara, Dolores Isla Casado, Raquel Andrés Conejero & Alejandro Tres Sánchez

  2. Hospital General de Alicante, La Coruña

    José Anadrés Meana García & Bartolomeu Massuti Sureda

  3. Hospital Juan Canalejo, La Coruña

    Manuel Valladares Ayerbes

  4. Hospital de Barbastro, Logroño

    Jesús Florián Jericó

  5. Hospital de Málaga, Logroño

    Juan José Bretón García

  6. Hospital de Terrassa, Logroño

    Remedios Blanco Guerrero

  7. Hospital San Millán, Logroño

    Carmen Santander Lobera

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  1. Elena Filipovich Vegas
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Correspondence to José Ignacio Mayordomo Cámara.

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Vegas, E.F., Cámara, J.I.M., García, J.A.M. et al. Bioquimioterapia ambulatoria con cisplatino, dacarbacina, interleucina-2 e interferón-alfa en pacientes con melanoma avanzado. Estudio multicéntrico en 44 pacientes. Rev Oncol 5, 79–87 (2003). https://doi.org/10.1007/BF02728200

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