title: Interleukin-2 and 13-cis retinoic acid in the treatment of minimal residual disease: a phase II study.
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 II 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: 1.8 x 106 IU and RA: 0.5 mg/kg for 5 days/week for 2 consecutive cycles of 3 weeks, with a 1-week rest, for up to 1 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.
authors.affiliation: Unità operativa di Oncologia, Ospedale Civile di Avezzano, Italy. franre@ermes.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Recchia
authors.forename: Sandro
authors.initials: S
authors.lastname: De Filippis
authors.forename: Michele
authors.initials: M
authors.lastname: Rosselli
authors.forename: Gaetano
authors.initials: G
authors.lastname: Saggio
authors.forename: Luca
authors.initials: L
authors.lastname: Fumagalli
authors.forename: Silvio
authors.initials: S
authors.lastname: Rea
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002097:C-Reactive Protein / Q000032:analysis; D018791:CD4 Lymphocyte Count; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage*; D015474:Isotretinoin / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D012217:Rheumatoid Factor / Q000097:blood
chemical_list: D007376:Interleukin-2; D002097:C-Reactive Protein; D012217:Rheumatoid Factor; D015474:Isotretinoin