Recombinant interleukin-2 and interferon-alpha-2a in pretreated advanced soft-tissue sarcomas

Fourteen patients with advanced soft tissue sarcomas (STS), all pre-treated with one or more chemotherapy (CT) lines, entered an outpatient phase 11 study in which subcutaneous recombinant Interleukin-2 (rIL-2) and intramuscular recombinant alpha-2a-interferon (r-alphaIFN) were concomitantly administered. Both the cytokines were given for 5 days/week for 3 consecutive weeks followed by a 2 weeks period during which only r-alphaIFN was administered. r-alphaIFN was provided at a dose of 3 x 10(6) International Units (IU), while rIL-2 was given at a dosage of 6 x 10(6)/m2/day IU (in 2 subcutaneous injections), starting from 2 x 10(6)/m2/day IU in the first week and progressively increasing to 4 and 6 x 10(6)/m2/day IU in the second and third weeks; in 4 patients the dose of 8 x 10(6)/m2/day IU was reached. Toxicity was moderate and correlated with rIL-2 dose; main side effects included changes in liver functionality tests (14/14), fever (13/14), fatigue (13/14), nausea and vomiting (9/14). In all 11 patients evaluable for response, stable disease (SD) was observed (duration 4-43 weeks; median 9 weeks); the median survival from the starting treatment was 18 weeks (range 10-52). In all treated patients, an immunological monitoring was performed: an increase in percentage (from 10 to 74%) and in absolute number (from 400 to 4.500 cells/mm3) of CD16+ lymphocytes (NK cells) was observed in the majority of cases. Our data indicate that this regimen can be administered in pre-treated and severely immunocompromised patients with minimal to moderate toxicity on ambulatory and home bases, with acceptable clinical results.