A phase II trial to evaluate gefitinib as second- or third-line treatment in patients with recurring locoregionally advanced or metastatic cervical cancer

Background. Cancer of the cervix occurs in similar to 500 000 women worldwide each year, with prognosis highly dependent on disease stage at diagnosis. Survival times are poor and therapy options are limited for patients who relapse following radiotherapy and chemotherapy regimens, suggesting alternative treatments are required. Evidence suggests the epidermal growth factor receptor (EGFR) is expressed at moderate to high levels in cervical carcinomas. We investigated whether gefitinib (IRESSA), an EGFR tyrosine kinase inhibitor, is a potential second- or third-line treatment option for women with recurrent cervical cancer. Methods. This was a multicenter, open-label, non-comparative, phase II trial (study 1839IL/0075) evaluating the clinical outcomes of 500 mg/ day gefitinib. An exploratory objective was to investigate the correlation of baseline EGFR expression with tumor response and disease control. Results. Thirty patients with squamous-cell carcinoma or adenocarcinoma were recruited from six centers in France. Of these, 28 patients were evaluable for efficacy. Although there were no objective responses, six (20%) patients experienced stable disease with a median duration of 111.5 days. Median time to progression was 37 days and median overall survival was 107 days. Disease control did not appear to correlate with levels of EGFR expression. Gefitinib was well tolerated, with the most common drug-related adverse events being skin and gastrointestinal toxicities. Conclusions. In recurrent disease resistant to standard treatment, gefitinib has only minimal monotherapy activity. However, the observation that 20% of patients treated with gefitinib had stable disease may warrant further investigation. (c) 2007 Elsevier Inc. All rights reserved.