Cisplatin-DNA adduct formation in patients treated with cisplatin-based chemoradiation: lack of correlation between normal tissues and primary tumor.
OBJECTIVE
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/m(2)) cisplatin, weekly 40 mg/m(2), three-weekly 100 mg/m(2). A (32)P-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 adenosine-guanosine-adducts in normal and tumor tissue. Adduct levels in tumors were two to five times higher than those in WBC (P<0.001). No significant 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 significantly 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.
Hoebers
F J P
FJ
Department of Radiotherapy, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. f.hoebers@nki.nl
Pluim
D
D
Hart
A A M
AA
Verheij
M
M
Balm
A J M
AJ
Fons
G
G
Rasch
C R N
CR
Schellens
J H M
JH
Stalpers
L J A
LJ
Bartelink
H
H
Begg
A C
AC
D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy; D002945:Cisplatin / Q000009:adverse effects* / Q000627:therapeutic use; D003131:Combined Modality Therapy; D018736:DNA Adducts / Q000187:drug effects*; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy; D006801:Humans; D007958:Leukocyte Count; D009061:Mouth Mucosa / Q000166:cytology; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy; D011237:Predictive Value of Tests
D000970:Antineoplastic Agents; D018736:DNA Adducts; D002945:Cisplatin