PURPOSE: This outpatient multicenter trial tested the hypothesis that subcutaneous administration of an interleukin-2 (IL-2)/interferon alfa (IFN alpha) combination produces a response rate greater than 20% in patients with renal cell carcinoma (RCC). PATIENTS AND METHODS: Patients with metastatic RCC received a 12-week induction treatment with subcutaneous IL-2 (5 days/wk, 9 and 18 million U/d)/IFN alpha (3 days/wk, 6 million U/d). After evaluation, patients with objective response or stable disease were randomly assigned to maintenance treatment or short consolidation treatment. RESULTS: Lack of benefit was shown at the 12th sequential analysis, and the trial was closed. At the end of the induction period, 26 (21%) of 122 patients had objective responses (including six complete responses). Thirty-three patients (27%) developed severe toxicity requiring dose reductions, delayed treatment, or treatment termination. Survival rates at one, two, and four years were 63%, 38%, and 17%, respectively. Three-year survival was 20% in patients with two poor prognosis factors and 37% in patients with one or no poor prognosis factors (P =.016). Three-year survival was significantly better (P < 10-3) in patients with erythrocyte sedimentation rate less than 35 mm (43%) compared with those with 1-hour sedimentation rate greater than 35 mm (19%). CONCLUSION: This study confirms the importance of prognostic factors when initiating cytokine immunotherapy in patients with metastatic RCC and underlines the prognostic value of erythrocyte sedimentation rate before treatment initiation. Nonetheless, this subcutaneous IL-2/IFN alpha combination does not improve response rate or survival compared with subcutaneous IL-2 alone, although a definitive conclusion cannot be drawn in the absence of a randomized study comparing the two treatments.
RCT Entities:
PURPOSE: This outpatient multicenter trial tested the hypothesis that subcutaneous administration of an interleukin-2 (IL-2)/interferon alfa (IFN alpha) combination produces a response rate greater than 20% in patients with renal cell carcinoma (RCC). PATIENTS AND METHODS: Patients with metastatic RCC received a 12-week induction treatment with subcutaneous IL-2 (5 days/wk, 9 and 18 million U/d)/IFN alpha (3 days/wk, 6 million U/d). After evaluation, patients with objective response or stable disease were randomly assigned to maintenance treatment or short consolidation treatment. RESULTS: Lack of benefit was shown at the 12th sequential analysis, and the trial was closed. At the end of the induction period, 26 (21%) of 122 patients had objective responses (including six complete responses). Thirty-three patients (27%) developed severe toxicity requiring dose reductions, delayed treatment, or treatment termination. Survival rates at one, two, and four years were 63%, 38%, and 17%, respectively. Three-year survival was 20% in patients with two poor prognosis factors and 37% in patients with one or no poor prognosis factors (P =.016). Three-year survival was significantly better (P < 10-3) in patients with erythrocyte sedimentation rate less than 35 mm (43%) compared with those with 1-hour sedimentation rate greater than 35 mm (19%). CONCLUSION: This study confirms the importance of prognostic factors when initiating cytokine immunotherapy in patients with metastatic RCC and underlines the prognostic value of erythrocyte sedimentation rate before treatment initiation. Nonetheless, this subcutaneous IL-2/IFN alpha combination does not improve response rate or survival compared with subcutaneous IL-2 alone, although a definitive conclusion cannot be drawn in the absence of a randomized study comparing the two treatments.
Authors: Dalil Hannani; Marie Vétizou; David Enot; Sylvie Rusakiewicz; Nathalie Chaput; David Klatzmann; Melanie Desbois; Nicolas Jacquelot; Nadège Vimond; Salem Chouaib; Christine Mateus; James P Allison; Antoni Ribas; Jedd D Wolchok; Jianda Yuan; Philip Wong; Michael Postow; Andrzej Mackiewicz; Jacek Mackiewicz; Dirk Schadendorff; Dirk Jaeger; Inka Zörnig; Jessica Hassel; Alan J Korman; Keith Bahjat; Michele Maio; Luana Calabro; Michele Wl Teng; Mark J Smyth; Alexander Eggermont; Caroline Robert; Guido Kroemer; Laurence Zitvogel Journal: Cell Res Date: 2015-01-13 Impact factor: 25.617
Authors: S Negrier; E Jäger; C Porta; D McDermott; M Moore; J Bellmunt; S Anderson; F Cihon; J Lewis; B Escudier; R Bukowski Journal: Med Oncol Date: 2009-09-12 Impact factor: 3.064
Authors: J Atzpodien; H Kirchner; U Rebmann; M Soder; U Gertenbach; M Siebels; J Roigas; R Raschke; S Salm; B Schwindl; S C Müller; S Hauser; C Leiber; E Huland; H Heinzer; S Siemer; B Metzner; H Heynemann; P Fornara; M Reitz Journal: Br J Cancer Date: 2006-08-08 Impact factor: 7.640