This trial was designed to investigate the anti-tumor and immunological effects of chronic IL-2 administration. In previous BRMP-sponsored studies, it has been demonstrated that ecdogenous LAK activity and anti-tumor responses may be produced by IL-Z administration alone, employing the treatment schedule and dosages used in this trial, without the severe toxicity and complicated ex vivo laboratory manipulations of LAK/IL-2 regimens. These prior studies have shown that in some patients, chronic outpatient administration of IL- alone can result in a sustained level of circulating LAK cells. In this investigation, 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 achieve a sustained circulating level of Leu-19 positive cells. At the end of 3 months of treatment, tumor response is assessed. No tumor responses have been seen. Patients have achieved maximum Leu-19 levels in the range of 50% of circulating mononuclear cells and elevations of white blood counts ranging above 50,000/cu mm. Circulating levels of LAK activity have been demonstrated. LAK activity and Leu-19 levels have been adequately sustained in most patients in the outpatient phase of treatment, suggesting that combination treatments may be designed around this IL-2 regimen, involving other BRMs, chemotherapy, monoclonal antibodies, etc., which might exploit or enhance the sustained levels of circulating cytotoxic cells for greater anti-tumor response. The current trial will be closed to further entry of patients after 15 evaluable patients have been treated, and is being redesigned to include moderate dose of cyclophosphamide to reduce suppressor cell populations.
