title: Pulse infusion interleukin-2 with famotidine and cyclophosphamide has activity in previously treated metastatic melanoma.
abstract: There is no established systemic therapy for patients with stage IV melanoma refractory to prior systemic treatment. Interleukin-2 (IL-2) is capable of inducing T-lymphocyte cytotoxicity against melanoma in vitro and in vivo. Famotidine may enhance the activity of T-cells further by allowing for increased IL-2 internalization by the IL-2 receptor on lymphocytes. Cyclophosphamide may decrease the immunosuppressive effects of regulatory T-cells. Daily short intravenous (i.v.) infusions (pulses) of IL-2 were used to treat 14 patients with metastatic melanoma, all of whom had experienced disease progression despite prior systemic therapy. The patients received 21.6 million IU/m(2) of pulse IL-2 i.v. for 15-30 minutes, preceded by 20 mg of famotidine i.v. (13) patients received 350 mg/m(2) of cyclophosphamide i.v. on day 1 (1 patient did not). Eight (8) patients were treated in an oncology inpatient unit while, most recently, 6 patients have received therapy on an outpatient basis. The cycles were repeated every 3 weeks until disease progression occurred. The patients included 10 males with a median age of 56 (range 31-87) with an Eastern Cooperative Oncology Group performance status of -1 (range 0 - -1). Common metastatice sites included lymph nodes (13), lungs (8), liver (4), and subcutaneous (4). Prior systemic therapy included IL-2 (11), interferon (7), and chemotherapy (7). The median number of cycles the patients underwent was 3 with a range of 1-7. The most common toxic reactions were fever, rigors, nausea/emesis, hypomagnesemia, and hypophosphatemia. One complete response and four partial responses were observed (response rate, 36%; 95% confidence interval: 14%-64%). Responses occurred in the lungs, liver, lymph nodes, and subcutaneous sites. The median response duration was 3.4 months, with a median survival of 8.3 months for the entire group. Six (6) patients remain alive with a median survival of 10.3 months. Pulse IL-2 with famotidine and cyclophosphamide produced activity in previously treated patients with melanoma and may be given on an outpatient basis to selected individuals.
authors.affiliation: Loma Linda University School of Medicine, Loma Linda, CA 92354, USA. wquan@llu.edu
authors.forename: Walter
authors.initials: W
authors.lastname: Quan
authors.forename: Charles
authors.initials: C
authors.lastname: Knupp
authors.forename: Francine
authors.initials: F
authors.lastname: Quan
authors.forename: Paul
authors.initials: P
authors.lastname: Walker
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary; D003520:Cyclophosphamide / Q000008:administration & dosage; D004333:Drug Administration Routes; 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; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D010166:Palliative Care
chemical_list: D007376:Interleukin-2; D015738:Famotidine; D003520:Cyclophosphamide