High-dose, continuous infusion
interleukin-2 (IL-2) regimens generate greater Lymphokine Activated Killer cell (LAK) cytotoxicity in vitro and a higher rebound
lymphocytosis in vivo than do bolus
IL-2 regimens. Lymphocytes initially activated by continuous infusion
IL-2 then subsequently pulsed with
IL-2 have increased cytotoxicity against
cancer cells.
Famotidine may enhance the lysis of
tumors by cytotoxic lymphocytes. Fourteen patients with
melanoma were treated with
famotidine 20 mg intravenously twice per day and continuous infusion
IL-2 (18 MIU/sq m/24 hours) for 72 hours, followed by a 24-hour rest, then
IL-2 18 MIU/sq m over 15-30 minutes for 1 dose (12 patients) or daily for 3 doses (2 patients). Most common toxicities were
fever,
nausea/
emesis,
hypophosphatemia, hypomagnesemia, and rigors. Nine partial responses (64% response rate; 95% Confidence Interval: 39%-84%) have been seen. Median survival has not been reached at greater than 10 months. Two patients responding to
therapy showed an increase in detectable CD 56(+) cells in serial subcutaneous or lymph node biopsies, while 1 patient undergoing progression of disease had no such infiltrate. High-dose, 72-hour continuous infusion plus pulse
interleukin-2 with
famotidine has activity in
melanoma. CD 56(+) cells may play a role in responding patients.