title: A phase II trial of gefitinib and pegylated IFNα in previously treated renal cell carcinoma.
abstract: 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.
authors: University of California Davis Cancer Center, Sacramento, CA 95817, USA.
authors: Derek
authors: D
authors: Shek
authors: Jeff
authors: J
authors: Longmate
authors: David I
authors: DI
authors: Quinn
authors: Kim A
authors: KA
authors: Margolin
authors: Przemyslaw
authors: P
authors: Twardowski
authors: David R
authors: DR
authors: Gandara
authors: Paul
authors: P
authors: Frankel
authors: Chong-Xian
authors: CX
authors: Pan
authors: Primo N
authors: PN
authors: Lara
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D000077156:Gefitinib; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D016898:Interferon-alpha; D011799:Quinazolines; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a; D000077156:Gefitinib