Cisplatin-DNA adducts and protein-bound platinum in blood of testicular cancer patients.
DNA adducts formed by cisplatin [cis-diamminedichloroplatinum(II)] were measured in blood samples from 48 testicular cancer patients treated in four centers in Europe during four to six cycles with cisplatin infusions on five successive days (total samples, 112). Total protein-bound platinum (Pt) in blood was also measured (total samples, 84). The mean on the main DNA adduct, cis-Pt(NH3)2d(pGpG) (Pt-GG), was 0.75 fmol/microg DNA [standard deviation (SD) = 0.66] on the first day of the first cycle, increased after the infusion at day 5 of the cycle (mean 1.74 fmol/microg DNA, SD = 0.90) and decreased on the following day (mean 1.09 fmol/microg DNA, SD = 0.62). In subsequent cycles, there was a tendency to an increase in the mean Pt-GG levels. The values of protein-bound Pt in blood showed little reduction between day 5 and 6 of each cycle, and a stable increase during the course of the therapy. Strong correlations were seen between day 1, 5 and 6 of the first cycle for both Pt-GG and protein-bound Pt in blood. A strong correlation (r = 0.62, p < 0.001, 69 pairs) was found between the levels of Pt-GG and protein-bound Pt. Only two patients relapsed during the follow-up; therefore, the analysis of the association between Pt-GG levels and response to therapy was not informative. The results of this study suggest that DNA adducts formed by cisplatin at the beginning of chemotherapy are predictive of values found during later days and cycles, and that the value of protein-bound Pt in blood is predictive of the value of DNA adducts.
Boffetta
P
P
Unit of Environmental Cancer Epidemiology, International Agency for Research on Cancer, Lyon, France.
Fichtinger-Schepman
A M
AM
Weiderpass
E
E
van Dijk-Knijnenburg
H C
HC
Stoter
G
G
van Oosterom
A T
AT
Keizer
H J
HJ
Fosså
S D
SD
Kaldor
J
J
Roy
P
P
D000328:Adult; D000970:Antineoplastic Agents / Q000097:blood* / Q000627:therapeutic use; D002945:Cisplatin / Q000097:blood* / Q000627:therapeutic use; D018736:DNA Adducts / Q000097:blood*; D006147:Guanine / Q000097:blood; D006801:Humans; D008297:Male; D010984:Platinum / Q000097:blood*; D011485:Protein Binding; D013736:Testicular Neoplasms / Q000097:blood* / Q000188:drug therapy; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D018736:DNA Adducts; D010984:Platinum; D006147:Guanine; D002945:Cisplatin