A multicenter trial of interleukin-2 and low-dose cyclophosphamide in highly chemotherapy-resistant malignancies

Abstract The anti-tumor activity of high-dose recombinant interleukin-2 (IL-2) has been demonstrated in several recent preclinical and clinical studies. In an attempt to study possible synergistic effects with low-dose cyclophosphamide (CYC), a phase II clinical trial was initiated in 32 patients, 18 with malignant melanoma (MM) and 14 with renal cell carcinoma (RCC). The recombinant IL-2 (Cetus Corp., Emeryville, Ca, U.S.A.) was given once daily at 3 × 10 6 U/m 2 , as a 30-min infusion for 14 days in cycle I and for five days twice in cycles II and III, respectively; if tolerated, the dose was escalated to a maximum of 6 × 10 6 U/m 2 /day; the cycles, separated by 1-week treatment-free intervals, were each preceded by a single i.v. bolus of CYC at 350 mg/m 2 . The most prominent side-effects encountered in this trial consisted of a capillary leak syndrome, myalgia and fever requiring dose reduction in half of the patients during the first cycle. Given the limit of tolerable toxicities in a standard care unit, the regimen employed achieved minor anti-tumor activity. No objective responses were achieved in patients with RCC and a 15% remission rate (PR + MR) was seen in melanoma patients.