Hybrid High-dose Bolus/Continuous Infusion Interleukin-2 in Patients with Metastatic Melanoma: A Phase II Trial of the Cancer Biotherapy Research Group (formerly the National Biotherapy Study Group)

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: Discussionmentioning

confidence: 99%

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

Perez

et al. 2012

“…Dillman et al utilized a bolus of 36 MIU/sq m prior to a 72-hour continuous infusion of 18 MIU/sq m per day to be a pharmacokinetic equivalent of polyethylene glycol conjugated IL-2 in both melanoma and kidney cancer. 27,28 Response rates of 22% in melanoma and 9% in renal cancer were obtained. Bar et al used high-dose bolus IL-2 prior to leukapheresis of the resulting lymphocytes, in vitro activation of LAK cells, and subsequent reinfusion of the LAK with concurrent continuous infusion IL-2 approximately 18 MIU/sq m/day for up to 148 hours.…”

Section: Discussionmentioning

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.

“…The use of continuous infusion-based IL-2 regimens allows for the more frequent recycling of therapy in patients, largely because the degree of toxicity, in terms of hypotension requiring intensive care unit vasopressor support, pulmonary 13 edema necessitating mechanical ventilation, increased bilirubin, and anemia needing blood transfusion, appears less than what is noted with high-dose bolus regimens. [18][19][20][21][22][23] While it is frequently recommended that potential candidates for high-dose bolus IL-2 undergo routine pulmonary function testing, 7,[16][17][18]24 this has not been a requirement for all high-dose continuous infusion regimens because the incidence and/or degree of pulmonary edema may be less. 6,9,25,26 We have tended to utilize a strict examination of ECOG performance status, treating only patients who are asymptomatic or only having symptoms that allow them to reach a performance status of 1.…”

Section: Discussionmentioning

confidence: 99%

Administration of High-Dose Continuous Infusion Interleukin-2 to Patients Age 70 or Over

Ramirez²,

Taylor³

et al. 2005

High-dose bolus or continuous infusion interleukin-2-based therapy can cause capillary leak syndrome. Significant cardiovascular/hemodynamic events, including myocardial infarction, hypotension, pulmonary edema, and cardiac arrhythmia, have been described with such therapy. Concern over the toxicity of highdose interleukin-2 (IL-2) therapy has led to some clinicians excluding patients 70 years of age or over. We have treated 15 patients 70 years of age or over having an Eastern Conference Oncology Group (ECOG) performance status of 0 or 1, with therapy based on continuous infusion IL-2 18 MIU/sq m/24 hours for 72 hours. All patients underwent a pretreatment evaluation of cardiac status with a low-level stress or adenosine stress test. Cycles were typically repeated every 3 weeks for 4 cycles, then every 3-4 weeks thereafter. Patients were treated by oncology nurses in either the stem cell transplant (intermediate unit) or the oncology inpatient unit. Patient characteristics were: median age, 72 years (range, 70-83 years); tumor types: melanoma (10), kidney cancer (5); most common sites of disease: lung (11), lymph nodes (6), subcutaneous (3), liver (2); prior therapy included: none (8), outpatient IL-2 (5), other immunotherapy (4). Median number of cycles received: 3 (1-10). Most common toxicities were: fever, rigors, nausea, emesis, hypophosphatemia, and hypomagnesemia. Three patients required the use of dopamine for blood pressure support. Two patients declined further therapy. There were no treatment-related deaths. No patients required endotracheal intubation or transfer to an intensive care unit. One complete and 8 partial responses (60% response rate) have been seen. Responding sites include the lung, lymph node, intact kidney primary, and liver. Median survival has not been reached at over 14 months (range 3+-26+ months). Patients who are 70 years of age and older with an ECOG performance status of 0 or 1 are able to tolerate high-dose continuous infusion IL-2-based therapy and may respond to such treatment.