Interleukin-2 (IL-2) which has no cross-resistance with chemotherapy, has given responses in tumors resistant to chemotherapy, and shown to be more effective when tumor burden is low. 13-cis retinoic acid (RA) has immunomodulatory properties, potentially synergistic with IL-2. The objective of this pilot phase 11 study was to verify the immunomodulatory properties, activity and toxicity of outpatient immunotherapy with subcutaneous low dose IL-2 and oral RA, identified in a previous phase-I study, in patients with advanced solid cancer in whom a response or stable disease as a result of standard chemotherapy had been achieved. Eighty patients with advanced solid tumors after standard chemotherapy, were treated with IL-2: 1.8x10(6) IU and RA: 0.5 mg/ka for 5 days/week for 2 consecutive cycles of 3 weeks, with a I-week rest, for up to I year. A total of 511 courses of IL-2/RA therapy were administered (median 6.4 per patient). Tumor markers, T4/T8 ratio and NK were monitored every 2 months. Response evaluation was carried out every 4 months. After a median follow-up time of 31 months there was a statistically significant improvement in the number of total lymphocytes, T4/T8 ratio and NK after IL-2 and RA therapy. Responses and disease stabilization were maintained for a median time of 19.3 months. Six patients were converted from partial to complete response, while 5 patients progressed. Median survival time was not reached yet. Grade 2 cutaneous toxicity and fever were observed in 29 and 13% of patients, respectively. These preliminary data show that after chemotherapy the administration of low-dose subcutaneous IL-2 and oral RA is feasible and has low toxicity. A sustained increase in the immunological parameters known to be prognostically relevant was observed and a clear benefit on tumor response from immunotherapy was obtained in 7.5% of patients.

Interleukin-2 and 13-cis retinoic acid in the treatment ofMinimal residual disease. A phase II study.

REA, Silvio
2002-01-01

Abstract

Interleukin-2 (IL-2) which has no cross-resistance with chemotherapy, has given responses in tumors resistant to chemotherapy, and shown to be more effective when tumor burden is low. 13-cis retinoic acid (RA) has immunomodulatory properties, potentially synergistic with IL-2. The objective of this pilot phase 11 study was to verify the immunomodulatory properties, activity and toxicity of outpatient immunotherapy with subcutaneous low dose IL-2 and oral RA, identified in a previous phase-I study, in patients with advanced solid cancer in whom a response or stable disease as a result of standard chemotherapy had been achieved. Eighty patients with advanced solid tumors after standard chemotherapy, were treated with IL-2: 1.8x10(6) IU and RA: 0.5 mg/ka for 5 days/week for 2 consecutive cycles of 3 weeks, with a I-week rest, for up to I year. A total of 511 courses of IL-2/RA therapy were administered (median 6.4 per patient). Tumor markers, T4/T8 ratio and NK were monitored every 2 months. Response evaluation was carried out every 4 months. After a median follow-up time of 31 months there was a statistically significant improvement in the number of total lymphocytes, T4/T8 ratio and NK after IL-2 and RA therapy. Responses and disease stabilization were maintained for a median time of 19.3 months. Six patients were converted from partial to complete response, while 5 patients progressed. Median survival time was not reached yet. Grade 2 cutaneous toxicity and fever were observed in 29 and 13% of patients, respectively. These preliminary data show that after chemotherapy the administration of low-dose subcutaneous IL-2 and oral RA is feasible and has low toxicity. A sustained increase in the immunological parameters known to be prognostically relevant was observed and a clear benefit on tumor response from immunotherapy was obtained in 7.5% of patients.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11697/17350
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 20
  • ???jsp.display-item.citation.isi??? 20
social impact