Phase II trial of sequential subcutaneous interleukin-2 plus interferon alpha followed by sorafenib in renal cell carcinoma (RCC).

PURPOSE: Immunotherapy (IL-2 and INF-α) was the treatment of choice for advanced renal cell carcinoma (RCC) until antiangiogenic therapy with tyrosin kinase inhibitors was developed in the early 2000s. This clinical trial explored the efficacy and toxicity of sequential treatment of IL-2 plus INF-α followed by sorafenib. METHODS: Eligibility criteria included measurable, non-resectable, histologically confirmed predominantly clear cell RCC, no prior systemic treatment, and ECOG PS 0-2. The treatment regimen was a 6-week cycle of subcutaneous IL-2 at 9 × 10(6) IU on days 1-6 of weeks 1, 2, 4 and 5 plus s.c. INF-α at 6 × 10(6) IU on days 1, 3 and 5 of weeks 1-6. Responders received 6 additional weeks of this regimen. All patients received oral sorafenib (400 mg bid) after immunotherapy until disease progression. The primary endpoint was progression-free survival. RESULTS: Forty-one patients were enrolled, median age 57 years. ECOG was 0/1 in 17/20 patients, 35 patients had prior nephrectomy and 18 patients pure clear cell cancer. Median PFS was 7.4 months (95 % CI 6.5-13.1) and OS was 16.6 months (95 % CI not reached). In 36 patients evaluable for response, ORR was 44.4 % and control rate was 94.4 %. Most adverse events (AEs) were Grade 1 or 2 toxicities (84.7 %). During immunotherapy the most common AEs were pyrexia (82.9 %), asthenia (56.1 %) and anorexia (46.3 %), whereas during sorafenib were diarrhoea (48.8 %) and hand-foot syndrome (46.3 %). CONCLUSIONS: A sequential regimen of IL-2 and INF-α followed by sorafenib showed effectiveness and manageable toxicity in patients with advanced RCC.

Value of FDG-PET for monitoring treatment response in patients with advanced GIST refractory to high-dose imatinib. A multicenter GEIS study.

AIM: The aim of this study was to evaluate the utility of positron emission tomography with 18F-fluorodeoxyglucose (FDG-PET) in monitoring response in refractory GIST. METHODS: This multicenter study prospectively evaluated 21 patients with locally advanced and/or metastatic GIST refractory to with high-dose imatinib (800 mg/day) treated with doxorubicin 15-20 mg/m2/weekly for 4 cycles, followed by imatinib maintenance (400 mg/day). CT and FDG-PET were performed at baseline and after completion of therapy. RESULTS: Mean baseline tumor size on CT was 5.9 cm. Median progression-free survival (PFS) was 219 days (range 62-1108). Three out of 21 patients (14%) had partial responses (PR) under RECIST criteria, 12 patients (57%) remained stable (SD) and 6 showed progression (PD) of the disease during treatment (29%). Six patients had PR by FDG-PET, 15 showed SD (n=9) or PD (n=6) based on EORTC criteria. Patients with a PFS <6 mo showed a significantly higher ∑SUVmax at baseline (26.04±13.4) than those with PFS≥6 mo (9.82±5.0) (P<0.05). A correlation was found between PET response and PFS: PR 14±6.1 mo, SD 5.5±0.8 mo and PD 3.5±4.1 mo (P<0.05). A residual SUVmax <5 after treatment correlated with improved PFS (314±315 days vs 131±91 days) (P<0.01). Survival curves showed a significant association between PET response and PFS (P<0.05). Patients with wild-type genotype KIT (KIT-WT) showed a significantly lower baseline SUVmax (5.36±1.4) than non-WT KIT (8.40±3.6) (P<0.05). CONCLUSION: FDG-PET is useful in assessing response of GIST refractory to imatinib and correlates with the presence of KIT-WT. Baseline ∑SUVmax can predict response to treatment in this series.