00014: A PHASE II STUDY OF THE AGO OVARIAN CANCER STUDY GROUP (AGO-OVAR 2.6): ZD1839 IN COMBINATION WITH TAMOXIFEN IN REFRACTORY OVARIAN CANCER

ZD1839 (Gefitinib) is a new epidermal growth factor receptor tyrosine kinase inhibitor. Preclinical studies demonstrating its involvement in tamoxifen resistance. We evaluated the safety, and efficacy of tamoxifen 1 ZD1839 in ovarian cancer patients refractory to platinum-and taxane based therapy. 56 patients with epithelial ovarian carcinoma or cancer of the fallopian tube or peritoneum refractory to platinum-taxane based therapy were enrolled. Tamoxifen was given in a dose of 40mg daily and gefitinib of 500 mg daily) until progression or unacceptable toxicity. Refractory disease was defined as progression or relapse during 6 months after platinum- taxane based therapy. First-line treatment with platinum/taxane was administered in 15 patients, and 41 received one or more chemotherapies. Mean age was 59.6 years (range; 37-80 years). Dose reductions of Gefitinib to 250 mg/day was performed in 10 patients (14.9%) mainly due to diarrhea in 6 (10.7%) patients. Discontinuation of study medication occurred in 6 patients (10.7%) due adverse events. The most frequent drug related side effects were diarrhoea and acne like skin rash. There were no complete or partial response. Median time to progression was 58 days (95% CI, 55-71 days), median overall survival time was 253 days (95% CI, 137-355 days). This is the first trial investigating the combination of gefitinib and tamoxifen in patients with refractory ovarian cancer. Gefitinib in a does of 500 mg daily did not appear to be effective in the treatment of this heavily pretreated collective. The addition of tamoxifen did not result in a worsening of the toxicity profile.