Steven D. Creech

Adjuvant High-Dose Bolus Interleukin-2 for Patients With High-Risk Renal Cell Carcinoma: A Cytokine Working Group Randomized Trial

PURPOSE This prospective, randomized, controlled phase III trial assessed high-dose bolus interleukin-2 (IL-2) postoperatively in patients with high-risk renal cell carcinoma (RCC). PATIENTS AND METHODS Eligibility requirements were resected locally advanced (LA; T3b-4 or N1-3) or metastatic (M1) RCC, no prior systemic therapy, and excellent organ function. Randomized assignment was to one course of IL-2 (600,000 U/kg every 8 hours on days 1 to 5 and days 15 to 19 [maximum 28 doses]) or observation. The study was designed and powered to show an improvement in predicted 2-year disease-free survival (DFS) from 40% for the observation group to 70% for the treatment group. The accrual goal was 68 patients with LA disease, with 34 patients per treatment arm. Metastasectomy patients were to be analyzed separately because of their unpredictable natural history. RESULTS Sixty-nine patients were enrolled onto the study (44 LA and 25 M1 patients). Toxic effects of IL-2 were as anticipated; no unexpected serious adverse events or treatment-related deaths occurred. Early closure occurred when an interim analysis determined that the 30% improvement in 2-year DFS could not be achieved despite full accrual. Sixteen of 21 LA patients receiving IL-2 experienced relapse, compared with 15 of 23 patients in the observation arm (P =.73); in the LA group, three deaths occurred in the IL-2 arm, and five deaths occurred in the observation arm (P =.38). Analysis including metastasectomy patients made no difference in DFS or overall survival. CONCLUSION One course of high-dose bolus IL-2, though feasible, did not produce the ambitious clinically meaningful benefit anticipated when administered postoperatively to patients with resected high-risk RCC.

Response to treatment of hepatitis C in individuals with a recent history of intravenous drug abuse

OBJECTIVE:The aim of this study was to determine the rate of sustained response (SR) to high-dose daily interferon (IFN) therapy in prior drug abusers with chronic hepatitis C. This was a retrospective matched cohort study conducted at a tertiary care university hospital in a large urban area.METHODS:The 120 individuals in each cohort were treated by the same physicians at the same facility, using the same treatment protocol and management procedures. Each patient received 5 million units of IFN daily for at least 1 yr and usually longer.RESULTS:Both groups achieved a similar rate of SR (no i.v. drug abuse, 37% vs i.v. drug abuse, 33%). The end of treatment (ET) response rate was unexpectedly higher in the drug-abusing population as compared to that non–drug-abusing control subjects but fell during the follow-up period to achieve an SR similar to that of the non–drug-abusing controls. The side effects of IFN therapy were no greater in the prior drug abusing population than in the controls, although many in the drug-abusing group increased their dose of methadone to counteract IFN side effects.CONCLUSIONS:The SR rate achieved by intravenous drug abusers to high-dose, daily IFN is similar to that in a non–drug-abusing HCV positive population. Recent use of illicit drugs within a 6-month period of starting IFN therapy or continued methadone use during treatment does not seem to impair the response to IFN when the results are compared with those of a matched cohort of non–drug-abusing controls.

Bone mineral density among cirrhotic patients awaiting liver transplantation

Osteoporosis is an important and common complication in patients with chronic liver disease. The goal of this study was to determine the bone mineral density (BMD) in different subgroups among pretransplant cirrhotic patients. BMD of the lumbar vertebrae (L) and femoral neck (F) were obtained in 104 consecutive cirrhotic patients. Descriptive and inferential statistics were used to compare the BMD among various groups. The mean BMD in males (n = 54) and females (n = 50) at L were 1.28 ± 0.25 g/cm2 and 1.13 ± 0.20 g/cm2, respectively (P = .001); at F they were 1.03 ± 0.14 and 0.91 ± 0.17, respectively (P < .0001). Among males, BMD at L in Child‐Turcotte‐Pugh class B and C were 1.40 ± 0.21 and 1.13 ± 0.20, respectively (P = .001); at F they were 1.11 ± 0.10 and 0.93 ± 0.13, respectively (P < .0001). Among females, BMD at L in Child‐Turcotte‐Pugh class B and C were 1.27 ± 0.18 and 1.05 ± 0.16, respectively (P = .0003); at F they were 1.02 ± 0.16 and 0.83 ± 0.12, respectively (P = .001). The BMD in premenopausal females (n = 15) and postmenopausal females (n = 35) at L were 1.20 ± 0.19 and 1.11 ± 0.20, respectively (P = .15); at F they were 0.97 ± 0.17 and 0.88 ± 0.16, respectively (P = .12). The BMD in postmenopausal females on hormone replacement therapy (n = 19) and on no hormone replacement therapy (n = 16) at L were 1.07 ± 0.17 and 1.14 ± 0.23, respectively (P = .29); at F they were 0.85 ± 0.15 and 0.91 ± 0.18, respectively (P = .33). The BMD values between etiologic groups were not significantly different. The overall prevalence of osteopenia and osteoporosis were 34.6% and 11.5%, respectively, being significantly higher in females than in males. In conclusion, significant difference in BMD values exists between males and females, as well as between Child‐Turcotte‐Pugh class B and C patients with cirrhosis. In addition, there is no significant influence of menopausal status, hormone replacement therapy, and etiology of cirrhosis on BMD. (Liver Transpl 2004;10:648–653.)