title: A phase II study evaluating the effect of tamoxifen on DNA repair in melanoma patients treated with dacarbazine.
abstract: The addition of tamoxifen to dacarbazine containing chemotherapy regimens used in the treatment of melanoma, has been shown to increase response rates, but the mechanism of any interaction is uncertain. The object of this study was to determine whether the addition of tamoxifen to dacarbazine, would modify DNA repair in-vivo and cause an increase in O6-meG adducts in peripheral blood leucocytes. This would provide some insight into the nature of the interaction between these two drugs. Twenty three patients with metastatic malignant melanoma received dacarbazine (DTIC) 1 g/m2 every three weeks for a maximum of six cycles. Tamoxifen 20 mg daily, was started after the first cycle of chemotherapy and then taken continuously during the treatment. Adduct levels after the second cycle of treatment were significantly higher than those after the first cycle (p = 0.0001). A similar rise however, was also produced when a cohort of patients were given dacarbazine without tamoxifen during the second cycle of treatment. This study did not show an additional increase of O6-meG adducts when tamoxifen was administered and therefore this mechanism does not support a postulated interaction between tamoxifen and dacarbazine. This is in agreement with the recent randomised study which did not show any significant increase in response rate with the addition of tamoxifen.
authors.affiliation: Imperial Cancer Research Fund, Clinical Oncology Unit, Churchill Hospital, Oxford, U.K.
authors.forename: M P
authors.initials: MP
authors.lastname: Saunders
authors.forename: A J
authors.initials: AJ
authors.lastname: Salisbury
authors.forename: K J
authors.initials: KJ
authors.lastname: O'Byrne
authors.forename: V L
authors.initials: VL
authors.lastname: Souliotis
authors.forename: S M
authors.initials: SM
authors.lastname: Varcoe
authors.forename: D C
authors.initials: DC
authors.lastname: Talbot
authors.forename: S A
authors.initials: SA
authors.lastname: Kyrtopoulos
authors.forename: A L
authors.initials: AL
authors.lastname: Harris
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D004260:DNA Repair / Q000187:drug effects*; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000097:blood; D015996:Survival Rate; D013629:Tamoxifen / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D013629:Tamoxifen; D003606:Dacarbazine; D019853:O(6)-Methylguanine-DNA Methyltransferase