A phase II, open-label study of gefitinib (IRESSA) in patients with locally advanced, metastatic, or relapsed renal-cell carcinoma

Abstract

Epidermal growth factor receptor (EGFR) expression has been associated with clinical outcome in some studies of renal-cell carcinoma (RCC). We investigated the efficacy and safety of gefitinib (IRESSA), an EGFR tyrosine kinase inhibitor, in RCC patients. This phase II trial recruited 28 patients with advanced, metastatic, or relapsed RCC. Patients received oral gefitinib 500 mg/day. Objective responses (ORs) were assessed every 2 months according to RECIST. Baseline tumor biopsies were analyzed immunohistochemically for EGFR expression. At trial closure (March 2003), no ORs were seen but 14 patients (53.8%) had stable disease. At extended analysis (August 2004), median time to progression was 110 days (95% confidence interval [CI]: 55, 117); median overall survival was 303 days (95% CI 180, 444). Gefitinib was generally well tolerated. Skin rash and diarrhea were the most common drug-related adverse events (AEs) [54 and 39% of patients, respectively] and the most common drug-related grade 3/4 AEs (both 11%). The majority of tumor biopsies (91%) had > or =70% of tumor cells expressing membrane EGFR. Despite the lack of ORs in this study, disease control was observed in 53.8% of patients. Gefitinib was generally well tolerated and no unexpected drug-related AEs were observed.

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

“…A previous phase II trial showed that the combination of gefitinib and IFNa demonstrated a modest delay in disease progression in previously treated metastatic RCC with a mean PFS of 4.3 months, and a median overall survival (OS) of 11.4 months [26]. On the other hand, several phase II trials investigating gefitinib as a single agent in advanced RCC showed less promising results [27]. In one trial, treatment with single agent gefitinib did not result in any CR or PR, and 81% of patients had PD within 4 months of starting therapy [16].…”

Genomics of renal cell cancer — Does it provide breakthrough?

“…44 However, immunohistochemical studies indicated high heterogeneity regarding intratumoral EGFR protein expression. 24 Since both anti-EGFR antibody and EGFR-TK inhibitor therapies have been introduced in RCC management, 11,13,16 it is mandatory to determine the diagnostic criteria for such treatments. The anti-EGFR antibody therapies require the expression of the wtEGFR with intact extracellular ligand-binding domain, while the EGFR-TK inhibitors require an active TK enzyme (autophosphorylation).…”

Systemische Therapie des metastasierten Nierenzellkarzinoms

“…Der Einsatz des gegen c-KIT und die PDGF-Rezeptoren A und B gerichteten Imatinib (Glivec® [34]) sowie des gegen den EGF-Rezeptor gerichteten Gefitinib (Iressa® [17]) und Erlotinib (Tarceva®) zeigte als Monosubstanz keine klinische Wirksamkeit in initialen Studien beim NZK, sodass ein weiterer Einsatz dieser Substanzen fraglich erscheint. Lediglich Glivec® könnte aufgrund der häufigen ckit-Überexpression bei sarkomatoiden NZK eine Rolle in dieser auf die Immuntherapie nicht ansprechenden Subpopulation darstellen [8].…”