Nawazish Khan

Repeated Cycles with 72-Hour Continuous Infusion Interleukin-2 in Kidney Cancer and Melanoma

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.

Postpartum spontaneous dissection of the first obtuse marginal branch of the left circumflex coronary artery causing acute coronary syndrome: a case report and literature review

IntroductionSpontaneous coronary artery dissection is a rare but important cause of acute coronary syndrome. It can cause unstable angina, acute myocardial infarction, and sudden death. The condition commonly affects young females with about one-third of the cases occurring during pregnancy and the peripartum period. The diagnosis may occasionally be overlooked as the patients are often young and have no risk factors for coronary artery disease.Case presentationHere we report the case of a 29-year-old African American woman who presented with acute coronary syndrome due to spontaneous dissection of the first obtuse marginal branch of the left circumflex coronary artery at three weeks post-partum and recovered requiring only medical management, possibly by longitudinal distribution of the intramural hematoma leading to good distal flow.ConclusionsSpontaneous coronary artery dissection should be suspected in all young multiparous females presenting with chest pain in the peripartum period even in the absence of risk factors. Urgent diagnosis by angiography is required. It is recommended that treatment should be tailored to meet individual circumstances. Patients who present with single-vessel disease and hemodynamic stability, and who receive medical treatment with anticoagulation, nitrates and a beta-blocker, should experience good results.

Correlation between Pulmonary Edema and Response of Pulmonary Metastases to High Dose Continuous Infusion Interleukin-2 in Metastatic Melanoma and Kidney Cancer

Pulmonary Metastases to High Dose Continuous Infusion Interleukin-2 in Metastatic Melanoma and Kidney Cancer Walter D Y Quan Jr., Nawazish Khan, W Chris Taylor, Maria Ramirez, Mikhail Vinogradov, Paul R Walker. Medical Oncology and Hematology, Medical College of Ohio, Toledo, OH; Medicine, East Carolina University School of Medicine, Greenville, NC. High dose Interleukin-2 via high dose bolus or continuous infusion administration is able to induce the presence of lymphokine activated killer (LAK) cells. LAK are able to non-specifically lyse tumor cells. They are also able to lyse endothelial cells which may account for, at least in part, the capillary leak syndrome seen as one of the toxicities with this therapy (Damle, 1987; Miltenberg, 1987). A pulmonary manifestation of capillary leak syndrome is the presence of pulmonary edema. We postulated that capillary leak may actually be a mechanism by which LAK could conceivably reach pulmonary metastases or could be a reflection of damage of endothelial cells in vasculature supplying metastases and that capillary leak syndrome may actually correlate with response of pulmonary metastases. We examined our data base of patients with lung metastases treated with high dose continuous infusion IL-2 (18 Million IU/sq m/day for 3 days) regimens. 18 patients had the following characteristics: melanoma (11), renal cancer (7), median age 67 (range 28–79), males 15. All patients were treated by oncology nurses on either the stem cell transplant unit or oncology ward. Pulmonary edema was defined as the presence of pleural fluid on chest x-ray, CT scan, and/or as noted on physical examination by at least 2 observers. No patients required endotracheal intubation/mechanical ventilation or intensive care unit transfer. Median number of cycles received 1⁄4 5 (range:1–13). All 8 responding patients (6 with melanoma, 2 with kidney cancer) manifested pulmonary edema during Interleukin-2 infusion. Four patients with pulmonary edema were non-responders. The presence of pulmonary edema correlated with response to therapy (P 1⁄4 0.01). See table 1. Median duration of response of pulmonary nodules 1⁄4 5 months (range:1–16 months). There is a correlation between development of pulmonary edema and response of pulmonary metastases in patients with melanoma and kidney cancer treated with high-dose continuous infusion Interleukin-2.