BACKGROUND: Platinum-DNA adducts can be measured in peripheral blood cells, and high adduct levels have previously been correlated with favorable clinical response to platinum-based therapy in patients with germ cell tumors and ovarian cancer. METHODS: To evaluate the relationship between platinum-DNA adducts and clinical response to chemotherapy, 36 patients with germ cell tumors treated with cisplatin-based chemotherapy had platinum-DNA adducts assayed in leukocytes by atomic absorption spectrometry (AAS) and cisplatin-DNA enzyme-linked immunosorbent assay (ELISA). Three chemotherapy regimens were involved: cisplatin and etoposide (Regimen A); carboplatin and etoposide (Regimen B); and cyclophosphamide, vinblastine, dactinomycin, bleomycin, and cisplatin [VAB-6] with or without high dose carboplatin plus etoposide plus autologous bone marrow rescue (Regimen C). Blood samples were drawn before and after each cycle of chemotherapy. RESULTS: One hundred ninety-two blood samples were assayed by AAS and 137 by ELISA: DNA adducts measured by AAS and ELISA increased immediately after treatment and decreased during the intervening time before the next treatment. DNA adducts were measurable by both methods 4-8 weeks after the last cycle of therapy. The peak and mean adduct levels measured in samples drawn immediately after Cycles 1 and 2 and after all cycles were analyzed in terms of their relationship to clinical response. In contrast to numerous prior studies, a positive correlation was not observed between DNA adduct formation as determined by either AAS or ELISA and favorable clinical responses. CONCLUSIONS: This study demonstrated that peak and mean platinum-DNA adduct levels were influenced by the dose and schedule of the platinum analogue. For example, treatment with VAB-6 with or without high dose carboplatin and etoposide (Regimen C) resulted in significantly higher adduct levels when measured by AAS compared with Regimen A or B. Inconsistencies between studies regarding observed correlations of DNA adducts and treatment outcome may be attributable to differences in platinum analogue, dose, schedule, and timing of sample procurement. These factors must be considered in future studies.
BACKGROUND:Platinum-DNA adducts can be measured in peripheral blood cells, and high adduct levels have previously been correlated with favorable clinical response to platinum-based therapy in patients with germ cell tumors and ovarian cancer. METHODS: To evaluate the relationship between platinum-DNA adducts and clinical response to chemotherapy, 36 patients with germ cell tumors treated with cisplatin-based chemotherapy had platinum-DNA adducts assayed in leukocytes by atomic absorption spectrometry (AAS) and cisplatin-DNA enzyme-linked immunosorbent assay (ELISA). Three chemotherapy regimens were involved: cisplatin and etoposide (Regimen A); carboplatin and etoposide (Regimen B); and cyclophosphamide, vinblastine, dactinomycin, bleomycin, and cisplatin [VAB-6] with or without high dose carboplatin plus etoposide plus autologous bone marrow rescue (Regimen C). Blood samples were drawn before and after each cycle of chemotherapy. RESULTS: One hundred ninety-two blood samples were assayed by AAS and 137 by ELISA: DNA adducts measured by AAS and ELISA increased immediately after treatment and decreased during the intervening time before the next treatment. DNA adducts were measurable by both methods 4-8 weeks after the last cycle of therapy. The peak and mean adduct levels measured in samples drawn immediately after Cycles 1 and 2 and after all cycles were analyzed in terms of their relationship to clinical response. In contrast to numerous prior studies, a positive correlation was not observed between DNA adduct formation as determined by either AAS or ELISA and favorable clinical responses. CONCLUSIONS: This study demonstrated that peak and mean platinum-DNA adduct levels were influenced by the dose and schedule of the platinum analogue. For example, treatment with VAB-6 with or without high dose carboplatin and etoposide (Regimen C) resulted in significantly higher adduct levels when measured by AAS compared with Regimen A or B. Inconsistencies between studies regarding observed correlations of DNA adducts and treatment outcome may be attributable to differences in platinum analogue, dose, schedule, and timing of sample procurement. These factors must be considered in future studies.
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Authors: Heather A Enright; Michael A Malfatti; Maike Zimmermann; Ted Ognibene; Paul Henderson; Kenneth W Turteltaub Journal: Chem Res Toxicol Date: 2016-10-11 Impact factor: 3.739
Authors: Si-Si Wang; Maike Zimmermann; Hongyong Zhang; Tzu-Yin Lin; Michael Malfatti; Kurt Haack; Kenneth W Turteltaub; George D Cimino; Ralph de Vere White; Chong-Xian Pan; Paul T Henderson Journal: Int J Cancer Date: 2017-05-15 Impact factor: 7.396
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