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

Abstract

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.

Nursing Care of Patients Receiving High-Dose, Continuous-Infusion Interleukin-2 With Pulse Dose and Famotidine

“…Casal, Davis, & Rosenfeld, 1997;Quan, Brick, et al, 2004;Quan, Ramirez, et al, 2004;Schwartzentruber, 2001). Symptoms usually begin to dissipate within a few hours of completion of continuous-infusion IL-2.…”

“…Nausea is a common side effect of IL-2 treatment (Quan, Brick, et al, 2004;Quan, Ramirez, et al, 2004). Prophylactic dosing of ondansetron and dronabinol are effective in combating nausea.…”

“…Mucosal side effects may include stomatitis, glossitis, mucositis, and/or pharyngitis (Mavroukakis, Muehlbauer, White, & Schwartzentruber, 2001;Quan, Brick, et al, 2004;Quan, Ramirez, et al, 2004). Frequent mouth care using a sodium chloride and sodium bicarbonate ("salt and soda," or approximately 2 tablespoons of baking soda to 1 L normal saline) mouth rinse throughout treatment is encouraged.…”

“…Recently, researchers (Quan, Brick, et al, 2004;Quan, Ramirez, et al, 2004; found that a combination of IL-2 given as a continuous infusion for 72 hours (18 million IU/m² every 24 hours) with famotidine 20 mg IV every 12 hours, followed by a 24-hour rest period, then IL-2 18 million IU/m² over 15-30 minutes ("pulse" dose) produced promising results in patients with Eastern Cooperative Oncology Group performance status of 0 or 1 with metastatic melanoma or renal cell carcinoma. The cycle generally is repeated This material is protected by U.S. copyright law.…”

“…Although research has studied the side effects and response rates of IL-2 given as a high-dose bolus (600,000 IU/kg), a much smaller research base is emerging related to side effects and response seen with IL-2 given as continuous infusion followed by pulse dose IL-2 (Hank, Weil-Hillman, Surfus, Sosman, & Sondel, 1990;Quan, Ramirez, et al, 2004;. Given in this manner, IL-2 may become an even more effective tool against stage IV renal cell carcinoma or metastatic melanoma.…”