title: High-dose continuous infusion plus pulse interleukin-2 and famotidine in melanoma.
abstract: 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.
authors.affiliation: Division of Medical Oncology and Hematology, Medical College of Ohio, Toledo, OH 43614, USA. wquan@mco.edu
authors.forename: Walter
authors.initials: W
authors.lastname: Quan
authors.forename: Maria
authors.initials: M
authors.lastname: Ramirez
authors.forename: W Chris
authors.initials: WC
authors.lastname: Taylor
authors.forename: Mikhail
authors.initials: M
authors.lastname: Vinogradov
authors.forename: Nawazish
authors.initials: N
authors.lastname: Khan
authors.forename: Shawn
authors.initials: S
authors.lastname: Jackson
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary; D004359:Drug Therapy, Combination; D015738:Famotidine / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000008:administration & dosage*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D008198:Lymph Nodes; D008297:Male; D008545:Melanoma / Q000188:drug therapy*; D008875:Middle Aged; D011674:Pulse; D012878:Skin Neoplasms / Q000188:drug therapy*; D013602:T-Lymphocytes, Cytotoxic
chemical_list: D000970:Antineoplastic Agents; D007376:Interleukin-2; D015738:Famotidine