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

Abstract

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.

Inflammatory Signaling in Hypertension: Regulation of Adrenal Catecholamine Biosynthesis

“…IL-1 can also modify vascular reactivity to NE ( 85 ). Human cancer patients who receive high doses of IL-2 demonstrate hemodynamic changes which suggest decreased peripheral resistance but increased cardiac output, with an overall reduction in mean arterial pressure ( 86 , 87 ). Similar hemodynamic changes and hypotension are observed in experimental animals ( 88 , 89 ).…”

Continuous Infusion Interleukin-2 and Intravenous Famotidine in Metastatic Melanoma

“…Previously, we have described our experience in treating patients who are at least age 70 using continuous infusion IL-2. 41 Additionally, one third of our patients are alive at a median of 25ϩ months. We, therefore, believe that the combination of famotidine and IL-2 is an active regimen in melanoma, which can be used in older patients with good performance status.…”

Skin Lesions and Pressure Ulcers

“…In the treatment of melanoma with isolated limb perfusion, patients of increased age demonstrated similar response rates with no increase in local or systemic toxicity [95]. Similarly, in a small group of elderly patients treated with high-dose IL-2 for melanoma and other tumor types, there was no demonstrated increase in adverse events to warrant their exclusion in future studies [96]. Therefore, while chronological age itself may not affect the efficacy or toxicity of any particular therapy, practical considerations necessitate the careful evaluation of comorbid disease, functional and mental status, support network, and patient willingness to tolerate the difficult side effects of treatment.…”