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Cancer Chemother Pharmacol (2008) 61:10751081
DOI 10.1007/s00280-007-0545-1
SHORT COMMUNICATION
Cisplatin-DNA adduct formation in patients treated with cisplatin-based chemoradiation: lack of correlation between normal tissues and primary tumor
F. J. P. Hoebers D. Pluim A. A. M. Hart M. Verheij A. J. M. Balm G. Fons C. R. N. Rasch J. H. M. Schellens L. J. A. Stalpers H. Bartelink A. C. Begg
Received: 12 February 2007 / Accepted: 8 June 2007 / Published online: 18 July 2007 Springer-Verlag 2007
Abstract
Purpose In this study, the formation of cisplatin-DNA adducts after concurrent cisplatin-radiation and the relationship between adduct-formation in primary tumor tissue and normal tissue were investigated.
Methods Three intravenous cisplatin-regimens, given concurrently with radiation, were studied: daily low-dose (6 mg/m2) cisplatin, weekly 40 mg/m2, three-weekly 100 mg/m2. A 32P-postlabeling technique was used to quantify adducts in normal tissue [white blood cells (WBC) and buccal cells] and tumor.
Results Normal tissue samples for adduct determination were obtained from 63 patients and tumor biopsies from 23 of these patients. Linear relationships and high correlations were observed between the levels of two guanosine- and adenosineguanosine-adducts in normal and tumor tissue.
Adduct levels in tumors were two to Wve times higher than those in WBC (P < 0.001). No signiWcant correlations were found between adduct levels in normal tissues and primary tumor biopsies, nor between WBC and buccal cells. Conclusions In concurrent chemoradiotherapy schedules, cisplatin adduct levels in tumors were signiWcantly higher than in normal tissues (WBC). No evidence of a correlation was found between adduct levels in normal tissues and primary tumor biopsies. This lack of correlation may, to some extent, explain the inconsistencies in the literature regarding whether or not cisplatin-DNA adducts can be used as a predictive test in anticancer platinum therapy.
Keywords Chemoradiation Cisplatin DNA adducts Head and neck cancer Cervical cancer
F. J. P. Hoebers (&) A. A. M. Hart M. Verheij C. R. N. Rasch H. BartelinkDepartment of Radiotherapy, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlandse-mail: [email protected]
D. Pluim A. C. BeggDepartment of Experimental Therapy, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
A. J. M. BalmDepartment of Head and Neck Oncology and Surgery,The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital,...