The purpose of the study was to identify a comprehensive prognostic system of pretreatment clinical parameters in 425 patients (pts) with metastatic renal-cell carcinoma treated with different subcutaneous (s.c.) recombinant cytokine-based home therapies in consecutive trials. Treatment consisted of (A) s.c. interferon-a2a (INF-a), s.c. interleukin-2 (IL-2) (n ¼ 102 pts), (B) s.c. IFN-a2a, s.c. IL-2, and i.v. 5-fluorouracil (5-FU) (n ¼ 235 pts) or (C) s.c. IFN-a2a, s.c. IL-2, and i.v. 5-FU combined with p.o. 13-cis-retinoic acid (13cRA) (n ¼ 88 pts). Kaplan -Meier survival analysis, log-rank statistics, and Cox regression analysis were employed to identify risk factors and to create a multiple risk factor model. The following pretreatment risk factors were identified by univariate analysis: (1) three and more metastatic sites, (2) presence of liver, lymph node or bone metastases, (3) neutrophil count X6500 cells ml À1 , (4) serum lactate dehydrogenase level (LDH) X220 U l À1 , and (5) serum C-reactive protein level (CRP) X11 mg l À1 . Cox regression analysis with forward stepwise variable selection identified neutrophil count as the major prognostic factor (hazard ratio ¼ 1.9, Po0.001), while serum levels of LDH and CRP, time between diagnosis of tumour and onset of metastatic disease, number of metastatic sites, and bone metastases were significant but somewhat less important prognostic variables within the multiple risk factor model (hazard ratio p1.5). Patients were assigned to one of the three risk groups according to cumulative risk defined as the sum of simplified risk s.c.ores for six pretreatment variables. Low-, intermediate-, and high-risk patients achieved a median overall survival of 32+ months (95% CI 24, 43; 5-year survival of 27%), 18+ months (95% CI 15, 20; 5-year survival of 11%), and 8+ months (95% CI 6, 10; 5-year survival of 5%), respectively. These prognostic categories are helpful both in individual patient care and in the assessment of patients entering prospective clinical trials.

Our results established the safety and improved long-term therapeutic efficacy of sc-IL-2 plus sc-INF-alpha-2a-based outpatient immunochemotherapies, compared with sc-INF-alpha-2a/IV vinblastine.

We conducted a prospectively randomized clinical trial to compare the efficacy and safety of subcutaneous interferon-α2a, subcutaneous interleukin-2 and intravenous 5-fluorouracil as home therapy against oral tamoxifen in 78 patients with progressive metastatic renal cell carcinoma. Treatment courses consisted of interferon-α2a 5 × 106 IU m−2day 1 weeks 1 + 4; days 1, 3, 5 weeks 2 + 3; 10 × 106 IU m−2days 1, 3, 5 weeks 5–8; interleukin-2 10 × 106 IU m−2twice daily days 3–5 weeks 1 + 4; 5 × 106 IU m−2days 1, 3, 5 weeks 2 + 3; and 5-fluorouracil 1000 mg m−2day 1 weeks 5–8. The tamoxifen group received tamoxifen 80 mg twice daily over 8 weeks. Among 41 patients treated with interleukin-2, interferon-α2a and 5-fluorouracil there were 7 complete (17.1%) and 9 partial responders (21.9%), with an overall objective response rate of 39.1% (95% CI, 24.2–55.5). An additional 15 patients (36.6%) were stable throughout therapy. The overall survival was 24 months (range 5–76+). In 37 patients receiving tamoxifen no objective remissions occurred. 13 patients (35.1%) had stable disease and 24 patients (64.9%) showed continued disease progression. The overall survival was 13 months (range 3–73+). In summary, this home-based therapy regimen of interferon-α2a, interleukin-2 and 5-fluorouracil demonstrated significant therapeutic efficacy in patients with progressive renal cell carcinoma when compared to hormonal therapy. © 2001 Cancer Research Campaign  http://www.bjcancer.com