Interleukin-2/interferon-alpha2a/13-retinoic acid-based chemoimmunotherapy in advanced renal cell carcinoma: results of a prospectively randomised trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN)

Abstract

We performed a prospectively randomised clinical trial to compare the efficacy of four subcutaneous interleukin-2-(sc-IL-2) and sc interferon-alpha2a (sc-IFN-alpha2a)-based outpatient regimens in 379 patients with progressive metastatic renal cell carcinoma. Patients with lung metastases, an erythrocyte sedimentation rate < or =70 mm h(-1) and neutrophil counts < or =6000 microl(-1) (group I) were randomised to arm A: sc-IL-2, sc-IFN-alpha2a, peroral 13-cis-retinoic acid (po-13cRA) (n=78), or arm B: arm A plus inhaled-IL-2 (n=65). All others (group II) were randomised to arm C: arm A plus intravenous 5-fluorouracil (iv-5-FU) (n=116), or arm D: arm A plus po-Capecitabine (n=120). Median overall survival (OS) was 22 months (arm A; 3-year OS: 29.7%) and 18 months (arm B; 3-year OS: 29.2%) in group I, and 18 months (arm C; 3-year OS: 25.7%) and 16 months (arm D; 3-year OS: 32.6%) in group II. There were no statistically significant differences in OS, progression-free survival, and objective response between arms A and B, and between arms C and D, respectively. Given the known therapeutic efficacy of sc-IL-2/sc-INF-alpha2a/po-13cRA-based outpatient chemoimmunotherapies, our results did not establish survival advantages in favour of po-Capecitabine vs iv-5-FU, and in favour of short-term inhaled-IL-2 in patients with advanced renal cell carcinoma receiving systemic cytokines.

Figure 1

Trial profile.

Figure 2

Progression-free survival: Kaplan–Meier estimates. Arm A, sc-IL-2, sc-IFN-α2a, po-13-cis-retinoic acid; n=78; median PFS, 5 months; 3-year PFS, 8.8%. Arm B, sc-IL-2, sc-IFN-α2a, po-13-cis-retinoic acid, inhaled-IL-2; n=65; median PFS, 4 months; 3-year PFS, 10.8%. Arm C, sc-IL-2, sc-IFN-α2a, po-13-cis-retinoic acid, iv-5-FU; n=116; median PFS, 0 months; 3-year PFS, 7.8%. Arm D, sc-IL-2, sc-IFN-α2a, po-13-cis-retinoic acid, po-Capecitabine; n=120; median PFS, 4 months; 3-year PFS, 9.3%.

Figure 3

Overall survival: Kaplan–Meier estimates. Arm A, sc-IL-2, sc-IFN-α2a, po-13-cis-retinoic acid; n=78; median OS, 22 months; 3-year OS, 29.7%. Arm B, sc-IL-2, sc-IFN-α2a, po-13-cis-retinoic acid, inhaled-IL-2; n=65; median OS, 18 months; 3-year OS, 29.2%. Arm C, sc-IL-2, sc-IFN-α2a, po-13-cis-retinoic acid, iv-5-FU; n=116; median OS, 18 months; 3-year OS, 25.7%. Arm D, sc-IL-2, sc-IFN-α2a, po-13-cis-retinoic acid, po-Capecitabine; n=120; median OS, 16 months; 3-year OS, 32.6%.