This trial investigates the antitumor and immunological effects of chronic IL-2 administration. Endogenous LAK activity and antitumor responses have been produced by administering IL-2 alone with the treatment schedule and dosages used in this trial. This approach avoids the severe toxicity and complicated ex vivo laboratory manipulations of LAK/IL-2 regimens. IL-2 is given by 24-hour continuous infusion twice weekly for up to 4 weeks, at a dose of 3 x 107 U/m2 (BRMP units) per 24-hour infusion. Subsequent IL-2 doses are adjusted in the individual patient to sustain circulating Leu19+ cells. At 3 months, tumor response is assessed. Modest antitumor effect was seen in the initial trial (1 PR, 1 minor response in 17 patients). Patients also demonstrated bimodal Leu19+ populations: CD16+/Leu19 dim and CD16-/Leu19 bright. LAK activity and Leu19 levels have been sustained in most patients in the outpatient phase of treatment suggesting that combination treatments may be designed around this IL-2 regimen. A follow- on trial employed moderate doses of cyclophosphamide monthly to reduce suppressor cell populations. This trial showed a comparable ability to maintain sustained immunological enhancement with IL-2. This trial also showed modest evidence of antitumor effect (2 PRs, 1 minor response in 17 patients). Full analysis of the immunological data is underway. A second follow-on study (#8908) is being performed using a monoclonal antibody (R- 24) which mediates ADCC, with this IL-2 regimen, for melanoma.
