Prospective randomized trial of natural interferon-alpha versus natural interferon-alpha plus cimetidine in advanced renal cell carcinoma with pulmonary metastasis
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Purpose: In a preliminary non-randomized study, combination therapy with natural (i.e. non-recombinant) interferon-alpha plus cimetidine obtained a high response rate in patients with advanced renal cell carcinoma. We conducted a prospective randomized phase III trial to determine whether combination therapy with natural interferon-alpha plus cimetidine is superior to natural interferon-alpha alone in patients with advanced renal cell carcinoma with pulmonary metastasis. Methods: Patients received 5 million units (MU) natural interferon-alpha per day, five times a week, or the 5 MU natural interferon-alpha regimen plus a daily oral cimetidine. The primary and secondary end points were the response rate, and the time to progression (TTP), respectively. Results: Between April 1998 and March 2002, 71 patients from 32 institutions were randomly assigned to the 2 treatment groups. One patient in each group did not receive any natural interferon-alpha whatsoever. Two patients in the natural interferon-alpha alone group stopped treatment: on day 9 and on day 10, respectively. In the intent-to-treat analysis, 1 complete response (CR), 4 partial responses (PRs), 16 no changes (NCs), and 12 progressive diseases (PDs) were observed among the 36 patients in the interferon-alpha alone group with a response rate of 13.9%. Of the 35 patients in the natural interferon-alpha plus cimetidine group, there were two CRs, 8 PRs, 13 NCs, and 11 PDs, yielding a response rate of 28.6% (P=0.13). TTP ranged from 9 to 845 days (median 112 days) in the natural interferon-alpha-alone group, and from 31 to 1,568 days (median 125 days) in the natural interferon-alpha plus cimetidine group (P=0.87). Conclusions: Combined treatment with natural interferon-alpha plus cimetidine for advanced renal cell carcinoma did not result in a significant improvement in response rates or TTP compared to natural interferon-alpha therapy alone.
KeywordsCimetidine Natural interferon-alpha Pulmonary metastasis Renal cell carcinoma
The authors are indebted to Prof. J. Patrick Barron of the international Medical Communications Center of Tokyo Medical University for his review of this manuscript.
- Aass N, De Mulder PHM, Mickisch GHJ, Mulders P, van Oosterom AT, van Poppel H, Fossa SD, de Prijck L, Sylvester RJ (2005) Randomized phase II/III trial of interferon alfa-2a with and without 13-cis-retinoic acid in patients with progressive metastatic renal cell carcinoma: the European Organisation for Research and Treatment of Cancer, Genito-Urinary Tract Cancer Group (EORTC 30951). J Clin Oncol 23:4172–4178CrossRefPubMedGoogle Scholar
- Bui MH, Seligson D, Han KR, Pantuck AJ, Dorey FJ, Huang Y, Horvath S, Leibovich BC, Chopra S, Liao SY, Stanbridge E, Lerman MI, Palotie A, Figlin RA, Belldegrun AS (2003) Carbonic anhydrase IX is an independent predictor of survival in advanced renal clear cell carcinoma: implications for prognosis and therapy. Clin Cancer Res 9:802–811PubMedGoogle Scholar
- Creagan ET, Twito DI, Johansson SL, Schaid DJ, Johnson PS, Flaum MA, Buroker TR, Geeraerts LH, Veeder MH, Gesme DH Jr, Homburger HA (1991) A randomized prospective assessment of recombinant leukocyte A human interferon with or without aspirin in advanced renal adenocarcinoma. J Clin Oncol 9:2104–2109PubMedGoogle Scholar
- Japanese Urological Association, Japanese Pathological Society, and Japan Radiological Society (1999) General rules for clinical and pathological studies on renal cell carcinoma, 3rd edn. Kanehara, TokyoGoogle Scholar
- Kimura K (1984) A cooperative phase I-II study of HLBI in patients with malignant tumors. Jpn J Cancer Chemother 11:1324–1331Google Scholar
- Kumar A (1990) Cimetidine: an immunomodulator. Ann Pharmacother 24:289–295Google Scholar
- Mickisch GH, Garin A, van Poppel H, de Prijck L, Sylvester R, Member of the European Organisation for Research, Treatment of Cancer (EORTC) Genitourinary Group (2001) Radical nephrectomy plus interferon-alfa-based immunotherapy compared with interferon alfa alone in metastatic renal-cell carcinoma: a randomized trial. Lancet 358:966–970CrossRefPubMedGoogle Scholar
- Niijima T (1986) A study of clinical response of renal cell carcinoma to human lymphoblastoid interferon (MOR-22). J Jpn Soc Cancer Ther 21:1277–1284Google Scholar
- Wirth MP (1993) Immunotherapy for metastatic renal cell carcinoma. Urol Clin N Am 20:283–295Google Scholar