Randomized study of intravenous versus subcutaneous interleukin-2, and IFNalpha in patients with good prognosis metastatic renal cancer.

PURPOSE: Metastatic renal cancer patients with a single metastatic site are potentially amenable to interleukin 2 (IL-2) + IFN-alpha. A French immunotherapy intergroup multicenter trial assessed the potential benefit of i.v. over s.c. administration of IL-2 in this combination. EXPERIMENTAL DESIGN: Untreated patients with one metastatic site were randomized to continuous i.v. infusion (18 x 10(6) IU/m(2)/d; arm A) or twice daily s.c. injections (9 x 10(6) or 18 x 10(6) IU; arm B) of IL-2, associated with s.c. IFN-alpha (6 x 10(6) IU) 3 days per week in both arms. Tumor response was assessed (WHO criteria) at weeks 12 and 24 to 26. The primary end point was overall survival, with an expected 15% improvement at 4 years with i.v. IL-2. The planned sample size was 220 (80% power, 5% significance, one-sided test). Intent-to-treat analysis was done and survivals were compared using log-rank tests. RESULTS: From January 2000 to January 2005, 80 and 75 patients were randomized to arms A and B, respectively. Enrollment was stopped early because of low accrual; analysis was done at 42.5 months median follow-up. Patient characteristics were well balanced between groups. Response rates were 17.9% versus 21.3% in arms A and B. Progression-free survival rates were not significantly different. Overall survival difference was not significant: median 33 months (95% confidence interval, 27.0-40.2; P = 0.202). CONCLUSIONS: In combination with IFN-alpha in selected, good prognosis metastatic renal cell carcinoma patients, i.v. IL-2 offers no significant advantage over s.c. IL-2 and induces higher toxicity. Although i.v. IL-2 induced longer responses, it seems unreasonable to continue recommending this regimen after the recent introduction of more effective therapies.

Rituximab, fludarabine, and total body irradiation as conditioning regimen before allogeneic hematopoietic stem cell transplantation for advanced chronic lymphocytic leukemia: long-term prospective multicenter study.

To evaluate the efficacy and toxicity of reduced-intensity conditioning (RIC) combining fludarabine, low-dose total body irradiation (TBI) and rituximab before allogeneic hematopoietic stem cell transplantation (allo-HSCT) from human leucocyte antigen (HLA) identical siblings, we conducted a prospective study in patients ≤65 years old with advanced chronic lymphocytic leukemia (CLL) stage B or C in response after a salvage treatment. Conditioning included rituximab (375 mg/m² on day 5), fludarabine (30 mg/m² from day 4 to day 2), TBI (2 Gy on day 0), and rituximab (500 mg/m² on days 1 and 8). Forty patients were included, 34 (85%) were male with a median age of 54 years (range, 35-65 years), 38 (95%) were in B stage, and 2 were in stage C; only 7 patients (17%) were in complete response. Seven (17%) patients did not receive rituximab. Thirty-nine (98%) patients engrafted, 17 patients developed acute graft-versus-host disease (GVHD) grade ≥II with a cumulative incidence at 3 months of 44% (36-52) with a significant protective effect of rituximab (p = 0.02). The cumulative incidence of chronic GVHD was 29% (21-36) at 12 months for both limited and extensive forms. The median overall survival was not reached with 5-years probability of 55% (41-74). The multivariate analysis showed a positive effect of rituximab on overall survival and event-free survival (hazard ratio [HR] = 0.1 [0-0.6], p = 0.02; and HR = 0.1 [0-0.4], p = 0.035, respectively). The association of fludarabine, TBI, and rituximab is feasible, well tolerated, and allows better outcomes in advanced CLL.