A phase II trial of gefitinib and pegylated IFNα in previously treated renal cell carcinoma.

BACKGROUND

This study was conducted to evaluate the efficacy of the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib with pegylated-IFNα (PEG-IFNα) in patients with advanced renal cell carcinoma.

METHODS

Progression-free survival (PFS) rate at 6 months >50% was considered promising for further evaluation. Patients with unresectable or metastatic disease, unlimited prior therapies, and adequate performance status and end-organ function were eligible. PEG-IFNα was dosed subcutaneously once weekly (initially 6 μg/kg/week, later reduced to 4 μg/kg/week) for 12 weeks. Gefitinib was given 250 mg orally once daily until progression or intolerance.

RESULTS

Twenty-one patients were accrued. Fourteen patients had a prior nephrectomy, and twelve had prior systemic therapy. The 6-month PFS was 29% (95%CI 15-56%). Best responses by RECIST criteria: complete, partial (1, plus 3 unconfirmed) stable (Uhlman et al. Clin Cancer Res 1:913-920, 1995), and progression (Sirotnak et al. Clin Cancer Res 6:4885-4892, 2000). Response duration: complete response (35+ months) and partial response (2, 3, 3, 37 months). Median PFS and overall survival were 5.3 (95%CI 3-10.1) and 13.6 (95%CI 10.3-NA) months, respectively. Most common toxicities included myelosuppression, rash, and nausea.

CONCLUSIONS

Although generally well tolerated, gefitinib plus PEG-IFNα did not meet the pre-specified 6-month PFS rate >50%. Further evaluation of similar regimens would require appropriate molecular selection of subjects most likely to benefit. Thus, preclinical studies to determine candidate predictive markers for this combination are warranted.