Low dose interleukin-2 and 13-cis-retinoic acid as maintenance therapy in patients with solid tumors responsive to chemotherapy

After aggressive surgery and chemotherapy, patients (PTS) with advanced solid tumors have often an impaired immune function that may facilitate tumor relapse. We have demonstrated, in a phase IB study, that administering low-dose interleukin-2 (IL-2) and 13-cis retinoic acid (RA), there was a significant improvement of the immune function, with low toxicity, in PTS with advanced tumors that had been treated with aggressive surgery and chemotherapy (Clin Cancer Res 7: 1251-1257, 200 1). A further A phase 11 study (International J Oncology 20: 1275-82, 2002) showed the efficacy of IL-2/RA in improving immunological parameters and in prolonging response in the same category of PTS. Aim of this study was evaluate the clinical and laboratory outcome of 214 patients, with advanced solid tumors, that, after aggressive surgery and chemotherapy, were treated with: subcutaneous IL-2 1.8 x 10(6) IU and oral RA, 0.5 mg/Kg for 5 days/week for 2 cycles of 3 weeks, with a 1-week rest, for up to 2 years. After a median follow-up time of 31 months, there was a statistically significant improvement in the number of lymphocytes, T4/T8 ratio, NK, with respect to baseline values. Responses were maintained for a median time of 36.4 months, while median survival was not reached yet (57% of PTS alive). These data show that the administration of low-dose IL-2/RA determines, with a low toxicity, a sustained increase in the immunological parameters known to be prognostically relevant.