title: Thalidomide reduces serum C-reactive protein and interleukin-6 and induces response to IL-2 in a fraction of metastatic renal cell cancer patients who failed IL-2-based therapy.
abstract: Interleukin-2 (IL-2) has some antitumor activity in patients with renal cell carcinoma. It has been noted that response to IL-2 and prognosis may be adversely affected by elevated serum levels of C-reactive protein (CRP) or interleukin-6 (IL-6). We used thalidomide to treat patients with cancer-induced cachexia and noted that the drug significantly reduced serum levels of CRP and IL-6 to normal or near normal levels in a substantial fraction of patients. We tested whether thalidomide might potentiate the response of patients with renal cell carcinoma to IL-2. Four patients with metastatic renal cell carcinoma and high serum levels of CRP and IL-6 who had experienced disease progression on IL-2 were retreated with the same IL-2 regimen combined with thalidomide 300 mg p.o. daily. Two patients achieved good partial responses and 2 patients had prolonged disease stabilization with the combination of IL-2 plus thalidomide. The regimen was well tolerated without increased IL-2-associated toxicity. Reduction of serum CRP or IL-6 levels with thalidomide may enhance the responsiveness of renal cell carcinoma to IL-2. A Phase II study of the combination is in order. It is possible that the thalidomide-induced normalization of serum acute phase proteins might improve the response of other types of malignancy to IL-2 or other immune-based therapies.
authors.affiliation: Biotherapy Unit Institute of Oncology, Soroka, University Medical Center, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel. igalk@bgumail.bgu.ac.il
authors.forename: Igal
authors.initials: I
authors.lastname: Kedar
authors.forename: Wilmosh
authors.initials: W
authors.lastname: Mermershtain
authors.forename: Hefziba
authors.initials: H
authors.lastname: Ivgi
mesh_terms: D000328:Adult; D002097:C-Reactive Protein / Q000032:analysis*; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000188:drug therapy* / Q000556:secondary; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000097:blood*; D007680:Kidney Neoplasms / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D013792:Thalidomide / Q000627:therapeutic use*
chemical_list: D007376:Interleukin-2; D015850:Interleukin-6; D013792:Thalidomide; D002097:C-Reactive Protein