Acute Tumor Lysis Syndrome After Thalidomide Therapy in Advanced Hepatocellular Carcinoma

Abstract

Correspondence: Chien-Chang Lee, M.D., Department of Emergency Medicine, National Taiwan University Hospital, No.7 Chun-Shan South Road, Taipei, Taiwan. Telephone: 886-2-23123456-5925; Fax: 886-2-23223150; e-mail: chnchnglee@ha.mc.ntu.edu.tw Received August 2, 2005; accepted for publication October 19, 2005. ©AlphaMed Press 1083-7159/2006/$12.00/0 We read with great interest the article by Dr. Zhu and colleagues on the phase II study using the combination of epirubicin (Ellence®; Pfizer Pharmaceuticals, New York, http://www.pfizer.com) and thalidomide (Thalomid®; Celgene Corporation, Warren, NJ, http://www.celgene.com) in patients with advanced hepatocellular carcinoma (HCC) [1]. The authors describe how the combination therapy had limited activity in HCC, but that the main toxicities of thalidomide, including constipation, fatigue, and sensory neuropathy, were well tolerated. Recently, tumor lysis syndrome (TLS) has been reported in patients with multiple myeloma treated with thalidomide [2], but this complication has not been reported in HCC. We report, herein, a rare case of TLS after thalidomide therapy in an HCC patient to alert the clinician to this potentially life-threatening complication. A 62-year-old man presented to the emergency department with the acute onset of shortness of breath. He had a history of HCC diagnosed 6 months earlier, when an 8-cm hepatic tumor was found on screening sonography along with an elevated serum alpha-fetoprotein level of 7,426 ng/ml. The tumor was spanning the left and right hepatic lobes, making it unresectable on presentation. He underwent transarterial chemoembolization several times from August to November 2002, with partial response, and had had stable disease for 4.5 months. In April 2003, tumor recurrence was noted and compassionate thalidomide therapy was suggested. He had started to receive lowdose (200 mg every 24 hours) thalidomide monotherapy 2 weeks previously, and the dose was increased to 300 mg every 24 hours 5 days before this admission. On examination, jaundice and a distended abdomen with right upper quadrant tenderness were noted. Laboratory exams showed elevated serum creatinine (3.6 mg/dl) and lactate dehydrogenase (1,453 u/dl) levels, hyperkalemia (6.2 mg/ dl), hyperphosphotemia (6.8 mg/dl), hyperuricemia (11.4 mg/dl), and metabolic acidosis. Three weeks earlier, he had had normal renal function, with a serum creatinine level of 1.0 mg/dl (Table 1). Sonographic examination revealed a reduced tumor of 6 cm in diameter, compared with 9 cm 2 weeks earlier. Under the suspicion of TLS, thalidomide treatment was stopped. Symptomatic treatment with diuretics, allopurinol, and alkalinization and antihyperkalemia measures, such as insulin plus glucose infusion, were started. Because of rapid deterioration of renal function, hemodialysis was suggested. However, the family refused hemodialysis and transferred him to a hospice for palliative care. Two days later, he died of refractive hyperkalemia and ventricular arrhythmia. Blood and ascites culture did not yield any growth. Until now, few renal complications associated with thalidomide therapy have been reported [3–5]. Renal excretion is not the major route of elimination of thalidomide, with an excretion rate of only 0.7% [6]. Hyperkalemia has been reported in patients with multiple myeloma and pre-existing renal insufficiency, but not in those with normal renal function [3]. Elevated serum creatinine levels and hypocalcemia have been noted in some patients coadministered This material is protected by U.S. Copyright law. Unauthorized reproduction is prohibited. For reprints contact: Reprints@AlphaMedPress.com