A PHASE-II STUDY EVALUATING THE EFFECT OF TAMOXIFEN ON DNA-REPAIR IN MELANOMA PATIENTS TREATED WITH DACARBAZINE

The addition of tamoxifen to dacarbazine containing chemotherapy regim ens used in the treatment of melanoma, has been shown to increase resp onse rates, but the mechanism of any interaction is uncertain. The obj ect of this study was to determine whether the addition of tamoxifen t o dacarbazine, would modify DNA repair in-vivo and cause an increase i n O-6-meG adducts in peripheral blood leucocytes. This would provide s ome insight into the nature of the interaction between these two drugs . Twenty three patients with metastatic malignant melanoma received da carbazine (DTIC) 1g/m(2) every three weeks for a maximum of six cycles . Tamoxifen 20mg daily, was started after the first cycle of chemother apy and then taken continuously during the treatment Adduct levels aft er the second cycle of treatment were significantly higher than those after the first cycle (p=0.0001). A similar rise however, was also pro duced when a cohort of patients were given dacarbazine without tamoxif en during the second cycle of treatment. This study did not show an ad ditional increase of O-6-meG adducts when tamoxifen was administered a nd therefore this mechanism does not support a postulated interaction between tamoxifen and dacabazine. This is in agreement with the recent randomised study which did not show any significant increase in respo nse rare with the addition of tamoxifen.