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Phase II Trial of Recombinant Human Interleukin-4 in Patients With Advanced Renal Cell Carcinoma: A Southwest Oncology Group Study

Whitehead, Robert P.*; Lew, Danika; Flanigan, Robert C.; Weiss, Geoffrey R.§; Roy, Vivek; Glode, Michael L.; Dakhil, Shaker R.#; Crawford, E. David

Clinical Studies
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Advanced renal cell carcinoma is a chemoresistant disease. Immunotherapy with alpha interferon or interleukin (IL)-2 has produced response rates of approximately 15%, but better treatments are needed. IL-4 is a cytokine produced by activated CD4+ lymphocytes and has pluripotent activities including inhibiting the in vitro proliferation of human renal cell carcinoma cell lines. In this trial, patients were required to have a histologic diagnosis of renal cell adenocarcinoma with measurable disease and performance status (SWOG) of 0–1. Patients had to have adequate bone marrow, renal, and hepatic function as well as no clinically significant pulmonary or cardiac dysfunction. IL-4 was given by subcutaneous injection at a dose of 5 μg/kg/d, daily for 28 days followed by a 7-day rest period. Fifty-eight patients were registered with seven patients ineligible and two patients not analyzable because they did not receive treatment. In the 49 eligible and analyzable patients, there were no confirmed complete or partial responses. There was one unconfirmed partial response in retro-caval lymph nodes, but no verifying measurement was done. There were seven patients with stable disease, no response, 25 with increasing disease/progression, and 16 patients whose assessment was inadequate to determine response. The median time to progression was 3 months, and the median survival was 13 months. Toxicity was significant with the most common side effects nausea, vomiting, or diarrhea, followed by headache/pain and malaise/fatigue/lethargy. There were 13 instances of grade 4 toxicity that occurred in nine different patients. Unique toxicities included Bell's palsy in three patients and hypoglycemia in a previously well-controlled diabetic. Despite promising growth inhibitory and immunologic effects, IL-4 in this dose and schedule is not useful for the treatment of patients with disseminated renal cell carcinoma.

*University of Texas Medical Branch, Galveston, Texas; †Southwest Oncology Group Statistical Center, Seattle, Washington; ‡Loyola University Stritch School of Medicine, Maywood, Illinois; §University of Texas Health Science Center, San Antonio, Texas; ∥University of Oklahoma Health Science Center, Oklahoma City, Oklahoma; ¶University of Colorado, Denver, Colorado; #Wichita CCOP, Wichita, Kansas, U.S.A.

Received October 23, 2001; accepted May 9, 2002.

Address correspondence to Robert P. Whitehead, M.D., University of Texas Medical Branch, Division of Hematology/Oncology, 301 University Blvd., Galveston, TX 77555-0565, U.S.A. E-mail: rpwhiteh@utmb.edu. Reprint requests to Southwest Oncology Group (SWOG-9230) Operations Office, 14980 Omicron Drive, San Antonio, Texas 78245-3217, U.S.A.

© 2002 Lippincott Williams & Wilkins, Inc.