High-Dose Continuous Infusion Plus Pulse Interleukin-2 and Famotidine in Melanoma

Perez

et al. 2012

13 males/8 females, median age, 51 (range: 26-79), and median Eastern Cooperative Oncology Group performance status, 1; common metastatic sites: lymph nodes (16), lungs (14), subcutaneous (8), liver (7), and bone (7). Prior systemic therapy: chemotherapy (7); IL-2 (7); and interferon (5). Most common toxicities were myalgia/arthralgia, rigors, nausea/emesis, and mild elevation of liver function tests. No patients required hospitalization for toxicity of therapy. One patient (5%) has had a complete response (ongoing at 29+ months), while 4 other patients (19%) had partial responses (total response rate: 24%; 95% confidence interval: 9%-48%). Responses occurred in lung, spleen, bones, lymph nodes, and subcutaneous sites. Median response duration=20+ months. Outpatient intravenous IL-2 and famotidine has activity in melanoma.

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Outpatient Intravenous Interleukin-2 with Famotidine Has Activity in Metastatic Melanoma

Perez

et al. 2012

“…26 Previously, we found increased numbers of CD56-positive LAK at s.c. and lymph node metastatic sites responding to famotidine and continuous-infusion plus pulse IL-2 in melanoma patients. 28 Tsunoda et al described enhanced cytotoxicity of LAK owing to famotidine. 27 The increased cytotoxic ability 440 could be related to famotidine-enhanced internalization of IL-2 by LAK.…”

Section: Discussionmentioning

confidence: 99%

“…Patient eligibility requirements were similar to what we have previously published. 28,29 Patients were required to have an Eastern Cooperative Oncology Group (ECOG) performance status Յ1, estimated survival of at least 3 months, white blood cell count Ն3500/mm 3 , platelets Ͼ100,000/mm 3 , hemoglobin Ͼ9.0 gm/dL, and serum creatinine Ͻ2.0 mg/dL. Patients were excluded for any autoimmune disease, such as inflammatory arthritis, which could be exacerbated by IL-2, medical illness requiring corticosteroids or other immunosuppressive agents, current untreated brain metastases, history of significant cardiovascular disease, including myocardial infarction, congestive heart failure, primary cardiac arrhythmias, angina pectoris, or cerebrovascular accident.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Activity of Continuous Infusion Plus Pulse Interleukin-2 with Famotidine in Patients with Metastatic Kidney Cancer or Melanoma Previously Treated with Interleukin-2

Walker

et al. 2006

Self Cite

Lymphokine-activated killer (LAK) cells generated by high-dose continuous infusion interleukin-2 (IL-2) are able to nonspecifically lyse melanoma and kidney cancer cells. In vitro famotidine enhances cytotoxicity of LAK against tumor cells, possibly by increasing IL-2 uptake at the IL-2 receptor on lymphocytes. Outpatient IL-2 regimens typically have response rates of 15% or less, with most patients eventually experiencing progressive disease. Second-line therapy is, therefore, needed. We treated 11 patients (6 with metastatic melanoma; 5 having metastatic kidney cancer) who had previously experienced progressive disease on prior IL-2 regimens, with a combination of famotidine 20 mg intravenously (i.v.) twice per day and continuous-infusion IL-2 18 MIU/M2/24 hours x 72 hours, followed 24 hours later by a pulse IL-2 dose (18 MIU/M2 over 15 minutes). Cycles were repeated every 3 weeks. Patient characteristics were: 9 males, median age 63 years (range, 57-75), median Eastern Cooperative Oncology Group (ECOG) performance status: 1; most common metastatic sites: lungs, lymph nodes, and soft tissue/subcutaneous (s.c.); median number of cycles received: 4; most common toxicities were fever, nausea/emesis, hypophosphatemia, and hypomagnesemia. Five (5) patients (3 with melanoma, 2 with kidney cancer) have had partial responses. Two (2) patients with kidney cancer have been converted to complete responders with resection of residual disease, remaining without relapse at 5+ and 20+ months. Responding sites are lungs, lymph nodes, abdominal mass, and s.c. Median duration of response was 9.5 months. Median survival was 12 months. This combination has activity in patients with metastatic kidney cancer or melanoma who have received prior IL-2.

Continuous Infusion Interleukin-2 and Famotidine in Metastatic Kidney Cancer

Vinogradov

et al. 2006

Self Cite

Infusional interleukin-2 (IL-2) is able to elicit lymphokine-activated killer cell (LAK) cytotoxicity against kidney cancer in vitro and in vivo. Famotidine may be able to augment LAK cytotoxicity against neoplastic cells. Fifteen (15) patients were treated with continuous-infusion IL-2 (9-18 MIU/m2/24 hours) for 72 hours and famotidine 20 mg intravenously twice per day. Cycles were repeated every 3 weeks. These patients had a median age of 60 years (range, 29-72), had a median performance status of 1 (range, 0-1), and had metastatic sites, including lung, bone, lymph node, and liver. The most common toxicities of this regimen were hypophosphatemia, fever, nausea/emesis, rigors, elevated creatinine, and hypomagnesemia. One (1) complete and 6 partial responses have been seen (47% response rate). The median duration of response is 9 months. The median survival for all patients is 20 months. Five (5) patients are alive at a median of 36+ months. This combination of infusional IL-2 with famotidine is active in metastatic kidney cancer.