title: Continuous infusion interleukin-2 and antihistamines in metastatic kidney cancer.
abstract: A prior randomized trial suggested a possible survival advantage favoring the combination of histamine and subcutaneous interleukin-2 (IL-2), compared to IL-2 alone in patients with metastatic melanoma. It has been postulated previously that antihistamines may, therefore, actually be antagonistic to IL-2 and thus interfere with its antitumor activity. We have previously shown no such antagonistic effect in patients with melanoma receiving IL-2 and antihistamines when reviewing the known literature. We sought to determine whether there was any negative effect of the combination in patients with metastatic kidney cancer. A PubMed literature search between 1985 and 2005 was done. High-dose continuous (or constant) infusion (CIV) interleukin-2 was used as the reference therapy because of the relatively constant IL-2 levels generated by this approach. Studies in which cimetidine, ranitidine, or famotidine were regularly scheduled and administered concurrently with IL-2 were included. Thirteen studies were identified. A total of 47 patients responded to therapy. Total response rate = 22%; 95%; Confidence Interval: 17%-28%. Eleven complete responses were noted. Complete response rate = 5%; 95% Confidence Interval: 3%-9%. These response rates are consistent with previously noted IL-2 response rates. In this study of CIV IL-2 and antihistamines, this combination appears to be active in metastatic kidney cancer. There appears to be no negative effect of antihistamine on the CIV IL-2 response rate in this disease.
authors.affiliation: Division of Medical Oncology and Hematology, Medical University of Ohio at Toledo, Ruppert Center, 3120 Glendale Avenue, Toledo, OH 43614, USA.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Walker
authors.forename: Sadik A
authors.initials: SA
authors.lastname: Khuder
authors.forename: Walter D Y
authors.initials: WD
authors.lastname: Quan
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002927:Cimetidine / Q000627:therapeutic use; D015738:Famotidine / Q000627:therapeutic use; D006632:Histamine / Q000627:therapeutic use; D006634:Histamine H1 Antagonists / Q000627:therapeutic use*; D006635:Histamine H2 Antagonists / Q000627:therapeutic use; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000188:drug therapy*; D009362:Neoplasm Metastasis; D011899:Ranitidine / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D007376:Interleukin-2; D015738:Famotidine; D002927:Cimetidine; D006632:Histamine; D011899:Ranitidine