Activity of continuous infusion + pulse interleukin-2 with famotidine in metastatic melanoma.
High-dose interleukin-2 (IL-2), given via continuous intravenous (i.v.) infusion, induces lymphokine-activated killer (LAK) cell cytotoxicity against tumor cells. These LAKs exhibit enhanced cytotoxicity against tumor cells in vitro when they are subsequently pulsed with additional IL-2. Famotidine may increase LAK cytotoxicity against neoplastic cells by allowing for greater IL-2 uptake at the IL-2 receptor on lymphocytes. Twenty-three (23) patients received famotidine 20 mg i.v. twice per day and continuous-infusion IL-2 (18 MIU/m(2)/24 hours) for 72 hours, followed by a 24-hour rest, then 1-3 daily-pulse IL-2 doses of 18 MIU/m(2) over 15-30 minutes preceded by famotidine 20 mg i.v. Cycles were repeated every 3 weeks. The most common metastatic sites were lung, lymph node, and subcutaneous/soft tissue. The most common toxicities were fever, rigor, nausea/emesis, hypophosphatemia, hypotension, elevated creatinine, and pulmonary edema. There were no treatment-related deaths. One (1) complete (4%) and 9 partial responses (39%) were seen (43% total response rate; 95% confidence interval: 22%-65%). Median survival for all patients is 13 months. The combination of famotidine and high-dose continuous infusion + pulse IL-2 is active in metastatic melanoma.
Quan
Walter D Y
WD
Department of Medical Oncology, Division of Hematology/Oncology, Loma Linda University School of Medicine, 11234 Anderson Street, Loma Linda, CA 92354, USA. wqjr@embarqmail.com
Quan
Francine M
FM
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D018572:Disease-Free Survival; D015738:Famotidine / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000008:administration & dosage*; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology* / Q000628:therapy; D008875:Middle Aged; D016896:Treatment Outcome
D007376:Interleukin-2; D015738:Famotidine