Outpatient Experience With Moderate Dose Bolus Interleukin-2 in Metastatic Malignant Melanoma and Kidney Cancer

Perez

et al. 2012

Self Cite

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%

“…20 Our group has previously seen two responses in 7 patients with melanoma treated with outpatient intravenous IL-2. 8 We and other investigators have combined such daily intravenous IL-2 infusions with low-dose cyclophosphamide. Response rates in these studies have ranged from 4% to 36%.…”

Section: Discussionmentioning

confidence: 99%

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

Perez

et al. 2012

Self Cite

“…The single pulse IL-2 dose is based on prior outpatient data. 19 Famotidine may have several adjunctive functions. Osband et al described inhibition of suppressor T-cells by famotidine.…”

Section: Discussionmentioning

confidence: 99%

“…The pulse IL-2 dose was based on prior outpatient data. 18,19 Famotidine was given intravenously to ensure that no doses were lost as a result of nausea/emesis. This study was undertaken to determine the response rate, median duration of response, and median survival of patients with melanoma treated with this regimen.…”

Section: Introductionmentioning

confidence: 99%

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

Ramirez

Taylor

et al. 2004

While high-dose bolus inpatient interleukin-2 is generally given on 8-week cycles, continuous infusion interleukin-2 could potentially allow for more rapidly repeated cycles. Fourteen (14) patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1, having either kidney cancer (6) or melanoma (8), have been treated with continuous infusion (CIV) interleukin-2 (IL-2) 18 MIU/m(2)/24 hours for 72 hours. Cycles were repeated every 3 weeks up to 4 cycles, then every 3-4 weeks for 2 cycles, then every 6-8 weeks, until progression or intolerable toxicity. All patients received famotidine 20 mg intravenously (i.v.) twice per day during the 72-hour infusions. Patient characteristics included a median ECOG performance status of 1; median age = 63 (range: 25-79); most common metastatic sites: lung (9), bone (5), lymph nodes (5), and the liver (3). No patients with metastatic kidney cancer underwent a nephrectomy prior to interleukin-2. Median number of cycles received = 5 (1-9). No patients required Intensive Care Unit (ICU) admission. There have been no treatment-related deaths. Most common toxicities have been rigors, fever, nausea/emesis, and the reversible elevation of creatinine. One complete response and three partial responses (67% response rate; 95% confidence interval: 30%-90%) have been seen in kidney cancer, and two partial responses (25% response rate; 95% confidence interval: 7%-60%) have occurred in melanoma. Median survival has not been reached at >9+ months. Responding sites include the liver, bone, lung, lymph node and subcutaneous sites. Inpatient 72-hour continuous infusion interleukin-2 at this dose and schedule is well tolerated by patients with an ECOG performance status of 0 or 1 and has activity in kidney cancer and melanoma.

“…28,29 The pulse IL-2 dose was based on prior data. 30 Famotidine was given i.v. to provide for adequate serum levels, which might not occur if doses were lost owing to nausea/emesis.…”

Section: Introductionmentioning

confidence: 99%

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.