An open, non-randomized phase II study was carried out including all patients treated with whatever chemotherapy or combined modality regimen for whatever cancer who were in clinical objective response or stable disease (SD) for more than three months, to receive maintenance treatment with recombinant interleukin-2 (rIL-2) plus medroxyprogesterone acetate (MPA) plus antioxidant agents alpha-lipoic acid (ALA) and N-acetyl cysteine (NAC). The main study endpoints were clinical outcome and toxicity. The secondary endpoints were effects of treatment on cancer-related anorexia/cachexia syndrome (CACS) symptoms, on serum levels of proinflammatory cytokines, IL-2, C-reactive protein (CRP) and leptin as well as the evaluation of quality of life (QL). rIL-2 was administered at a dose of 1.8 MIU subcutaneously three times/week on alternate days for the first two weeks of every month and MPA was given orally at a dose of 500 mg once a day at alternate days without interruption. ALA 300 mg/day orally and NAC 1800 mg/day orally were also administered. The treatment was administered until progression of disease or appearance of toxicity. From July 1998 to May 2000, 16 patients were enrolled in the study (M/F ratio: 15/1; mean age: 62 years, range 45-71). The median duration of maintenance treatment was 10 months (range 5-22). The response to maintenance treatment at September 2000 was: CR (persistent throughout the treatment) 4 patients (25%); SD 1 patient (6.2%); PD 11 patients (68.8%). The median duration of response was 9.8 months (range: 5-22+). The median follow-up duration was 19 months (range: 8-102). The median OS was not reached. The median PFS was 14 months (range 1-29). The 1-year survival rate was 25%. At September 2000, 9 patients are still surviving. No grade 3/4 toxicity was observed. One Grade 2 skin toxicity was observed and Grade 1: 2 fever, 2 thrombocytopenia, 1 neutropenia and 1 skin were observed. The ECOG PS did worsen significantly, the body weight and BMI increased significantly after treatment, whereas the appetite did not change significantly. The QL evaluation showed a significant amelioration of cognitive functions and a borderline significant amelioration of emotional functions after treatment, whereas a borderline worsening of dyspnea was observed. The absolute lymphocyte count increased significantly after the maintenance treatment, as well as the serum IL-2, TNFα decreased at borderline statistical significance; the serum levels of leptin did not change significantly. The evaluation of patient subgroups showed that responders/survivors had a pattern superimposable to that of whole patient population, the patients who rapidly progressed and died exhibited no significant changes of these parameters during treatment. The results of the present study suggest that the host immune response, evaluated by several parameters, after IL-2 administration, (e.g. lymphocytosis), are worth further study as potential markers for the major end points of cancer treatment, i.e. OS and QL, in an adequate number of patients.

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