A phase-II study of low-dose cyclophosphamide and recombinant human interleukin-2 in metastatic renal cell carcinoma and malignant melanoma

Abstract

Recent preclinical and clinical studies that have demonstrated antitumor activity of high-dose recombinant interleukin-2 (rIL-2), and animal models that demonstrated a synergistic effect of low-dose cyclophosphamide, led us to study rIL-2 (Cetus Corp., Emeryville, Calif) in a phase II clinical trial in combination with low-dose cyclophosphamide in 32 patients, 18 with malignant melanoma and 14 with renal cell carcinoma. rIL-2 was given once daily at 3 x 10(6) U/m2, as a 30-min infusion for 14 days in cycle I and for 2 x 5 days in cycles II and III respectively; if tolerated, the dose was increased to a maximum of 6 x 10(6) U m-2 day-1; the cycles, separated by 1 week treatment-free intervals, were preceded each by a single i.v. bolus of cyclophosphamide at 350 mg/m2. The most prominent side-effects encountered in this trial consisted of a capillary leak syndrome, myalgia and fever that required dose reduction during the first cycle in one-half of the patients. Given the limit of tolerable toxicities in a standard care unit, the regimen employed achieved minor antitumor activity. No remission was achieved in patients with renal cell carcinoma, and 15% of melanoma patients showed objective responses (partial response + minor response).

Immune Modulating Effects of Low Doses of Cyclophosphamide and Keyhole Limpet Hemocyanine on Peripheral Blood Immune Parameters in Patients with Metastatic Renal Cell Carcinoma

“…Immune Modulation by KLH and Cyclophosphamide in Renal Cancer mor vaccines [27] or with tumor-infiltrating lymphocytes, respectively, which contain tumor-specific suppressor cells [40], Combination with unspecific immunoactivation by IL 2 [41], IFN-a [42] or KLH (present study) did not improve the clinical results.…”

Natural killer cells and cancer

“…Studies designed to use cyclophosphamide in conjunction with rIL-2 to prevent the induction of T suppressor lymphocytes have not resulted in improved responses in patients with advanced melanoma or renal cell carcinoma. 260 In most cases, IFN-a treatment of patients results in an increase in NK cell activity. However, the later is often transient and may be followed by depressed iictivity, which may be mediated by suppressor factors.'…”

Outpatient Intravenous Interleukin-2 with Famotidine Has Activity in Metastatic Melanoma

“…Response rates in these studies have ranged from 4% to 36%. 7,[21][22][23] Our approach in the current study allowed for the treatment of patients on an outpatient basis. While some degree of hypotension was common in this cohort of patients, all instances resolved with intravenous saline infusions.…”