High-dose intensity pulse interleukin-2 with famotidine has activity in metastatic melanoma.
Daily short intravenous (i.v.) infusions (pulses) of interleukin-2 (IL-2) have been developed to decrease toxicity while maintaining anticancer activity of this agent against melanoma. Such IL-2 schedules have previously been shown to promote lymphokine-activated killer (LAK) cell activity. Famotidine may increase LAK activity by increasing IL-2 internalization by the IL-2 receptor on lymphocytes. We treated 16 patients with metastatic melanoma using pulse IL-2 18 (15 patients) or 9 million IU/M2 (1 patient) i.v. over 15-30 minutes preceded by famotidine 20 mg i.v. daily for 5 days on an oncology inpatient unit. Cycles were repeated every 3 weeks until disease progression. Patient characteristics were as follows: 11 males, median age, 66, median ECOG performance status, 1; common metastatic sites: lymph nodes, lungs, subcutaneous, liver, and bone. Median number of cycles received was 3. Overall, 93% of planned doses were delivered. Most common toxicities were hypomagnesemia, fever, rigors, hypophosphatemia, and nausea/emesis. Three (3) patients had partial responses (19% response rate; 95% confidence interval: 6%-44%). A fourth patient, after resection of residual disease, remains a surgical complete responder at > 12 months. Responses occurred in lung, liver, lymph nodes, bone, and subcutaneous sites. Median response duration was 7 months. Pulse IL-2 with famotidine has activity in melanoma.
Quan
Walter D Y
WD
Division of Hematology/Oncology, Loma Linda University School of Medicine, Loma Linda, CA 92354, USA. wquan@llu.edu
Walker
Paul R
PR
Picton
Maria
M
Quan
Francine M
FM
King
Linda A
LA
Tyre
Charley
C
Liles
Darla K
DK
D000368:Aged; D000369:Aged, 80 and over; D003131:Combined Modality Therapy; D018450:Disease Progression; D015738:Famotidine / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use*; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000188:drug therapy*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D016896:Treatment Outcome
D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D015738:Famotidine