IL-2 in combination with IFN-αand 5-FU versus tamoxifen in metastatic renal cell carcinoma: long-term results of a controlled randomized clinical trial

Abstract

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

Immunotherapy of Metastatic Renal Cell Cancer

“…Fig 2 illustrates a comparison of schedules used in three combinations of 5-FU, IL-2, and IFN-α that have been reported with divergent response rates. [36][37][38] A direct, randomized comparison of high-dose inpatient IL-2 and an outpatient schedule restricted to patients who would otherwise be eligible for inpatient high-dose IL-2 has been presented (favoring the high-dose cohort, discussed later). 39 Improved tolerability would allow more patients to consider starting, as well as successfully complete, the treatment courses.…”

“…Estimates of CR and PR are generally in the 6% to 8% and 15% to 20% range, respectively, in larger series. [4][5][6][7] Smaller series with better rates, such as reported by Atzpodien et al, 38 appear difficult to reproduce, again probably related to case selection. Long-term survivorship is concentrated in subjects with CRs, and some improvement is also observed for PRs.…”

Metastatic renal carcinoma comprehensive prognostic system

“…While renal-cell carcinoma responds poorly to single-agent chemotherapy or hormonal therapy, immunotherapies with subcutaneous (s.c.) recombinant interleukin-2 (IL-2) alone or in combination with s.c. recombinant interferon-a (INF-a) yielded significant therapeutic efficacy in renal-cell carcinoma (Atzpodien et al, 1990(Atzpodien et al, , 2001(Atzpodien et al, , 2002Sleijfer et al, 1992).…”

Adjuvant treatment with interleukin-2- and interferon-alpha2a-based chemoimmunotherapy in renal cell carcinoma post tumour nephrectomy: Results of a prospectively randomised Trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN)

“…The lack of sc-rIL-2/sc-rIFN-a2a/iv-5-FU-related survival benefit in the adjuvant renal carcinoma therapy was disappointing, particularly when compared to the established efficacy in metastatic renal cell carcinoma patients (Lopez-Hänninen et al, 1996;Elias et al, 1999;Atzpodien et al, 2001Atzpodien et al, , 2004.…”

“…The combination of subcutaneous cytokines with the chemotherapeutic i.v. 5-fluorouracil (5-FU) further enhanced antineoplastic activity achieving objective response rates between 18 and 39% (Lopez-Hänninen et al, 1996;Dutcher et al, 2000;Atzpodien et al, 2001Atzpodien et al, , 2004. Based on its efficacy in metastatic renal cell carcinoma, we hypothesized that outpatient sc-rIL-2/sc-rIFN-a2a/iv-5-FU-based immunochemotherapy according to the standard Atzpodien regimen (Atzpodien et al, 2004) might extend progression-free and/or overall survival of high-risk renal cell carcinoma patients in the postsurgical adjuvant setting.…”