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Safety, tolerability and activity of gefitinib (ZD1839) in combination with tamoxifen in ovarian cancer patients refractory to platinum-taxane based therapy - a Phase-II study of the Ovarian Cancer Study Group (AGO Ovar 2.6).

5016 Background: To evaluate safety and tolerability of the combination of tamoxifen and gefitinib ('Iressa', ZD1839) in pts with refractory ovarian cancer.Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor, which in preclinical studies has demonstrated involvement in the inhibition of tamoxifen resistance.


PATIENTS AND METHODS
In this Phase II study, 57 pts with epithelial ovarian carcinoma refractory to platinum- and taxane-based therapy received oral tamoxifen (2 x 20 mg/day) and gefitinib (2 x 250 mg/day) until progression or unacceptable toxicity. Refractory pts are defined as those who progress or relapse during or within 6 mos after platinum- and taxane-based therapy. This interim analysis was based on data from 47 pts.


RESULTS
The median age was 60 years (37-80 yrs). 12 pts had received only first-line treatment with platinum/taxane, and 35 had received 1 or more further chemotherapy regimens. Gefitinib dose reductions to 250mg/day were carried out in 7 pts (14.9%) mainly due to diarrhea. Five pts prematurely discontinued trial medication due to adverse events (AEs). 26 pts (55.3%) stopped treatment due to disease progression. The most frequent drug related AEs were diarrhea 53.1% (40.4% grade 1/2, 10.6% grade 3/4, without grading 2.1% ) and acne-like skin rash 38.3% (23.4% grade 1/2, 4.3% grade 3/4, without grading 10.6%). Median time to progression was 58 days (95% CI: 55-70 days). One pt (2.1%) showed a complete response and 9 pts (19.1%) achieved stable disease. The proportion of pts alive after 6 mos was 56.6%.


CONCLUSION
This first trial showed the combination of tamoxifen and gefitinib being relatively well tolerated in pts with refractory ovarian cancer. These preliminary data provide evidence that the combination showed some clinical activity in pts with platinum- and taxane refractory ovarian cancer, and therefore, should be further evaluated. [Table: see text].