title: High-dose continuous infusion plus pulse interleukin-2 and famotidine in metastatic kidney cancer.
abstract: High-dose continuous infusion interleukin-2 (IL-2) regimens generate a higher degree of lymphokine activated killer cell (LAK) cytotoxicity when tested against tumor cells in vitro and a higher rebound lymphocytosis in vivo than do bolus IL-2 regimens. Lymphocytes initially activated by continuous infusion IL-2 have increased cytotoxicity against cancer cells when they are subsequently pulsed with additional IL-2. Famotidine may enhance LAK cytolytic ability. Six patients with kidney cancer have been treated with a combination of famotidine 20 mg intravenous bid 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. The most common metastatic sites were the lung, lymph node, and bone. Median number of cycles received = 5 (range, 3-8). The most common toxicities were fever, rigors, nausea/emesis, hypophosphatemia, hypotension, elevated creatinine, and metabolic acidosis. There were no treatment-related deaths, and no patients required intensive care admission. Two partial responses (33% response rate) have been seen. Median survival has not been reached at greater than 8 months. The combination of high-dose continuous infusion plus pulse IL-2 and famotidine is active in metastatic kidney cancer. An accrual of additional patients is needed to better assess the response rate.
authors.affiliation: Division of Medical Oncology and Hematology, Medical College of Ohio, Toledo, OH. wquan@mco.edu
authors.forename: Walter
authors.initials: W
authors.lastname: Quan
authors.forename: Maria
authors.initials: M
authors.lastname: Ramirez
authors.forename: Chris
authors.initials: C
authors.lastname: Taylor
authors.forename: Mikhail
authors.initials: M
authors.lastname: Vinogradov
authors.forename: Francine
authors.initials: F
authors.lastname: Quan
authors.forename: Nawazish
authors.initials: N
authors.lastname: Khan
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology; D003131:Combined Modality Therapy; D015738:Famotidine / Q000008:administration & dosage*; D005260:Female; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000378:metabolism; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D015979:Killer Cells, Lymphokine-Activated / Q000166:cytology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D006635:Histamine H2 Antagonists; D007376:Interleukin-2; D015738:Famotidine