Comparison of in vitro growth-inhibitory activity of carboplatin and cisplatin on leukemic cells and hematopoietic progenitors: the myelosuppressive activity of carboplatin may be greater than its antileukemic effect.
BACKGROUND
Carboplatin [cis-diammine(cyclobutane-1, 1-dicarboxylato)platinum(II)] has been shown to be an active agent for acute myeloid leukemia. This second-generation platinum drug has less nephrotoxicity and ototoxicity but more myelotoxicity than does the first-generation platinum drug cisplatin. The study was designed to elucidate whether their myelosuppressive activities equal their antileukemic effects.


METHODS
Cisplatin and carboplatin were used to treat four leukemic cell lines (CEM, HL60, K562 and U937), blast cells from 10 leukemic patients and hematopoietic progenitors from five umbilical cord blood samples.


RESULTS
The mean IC50 of leukemic cell lines was 0.4 and 6.2 microg/ml, the mean IC50 of patients' leukemic blasts was 2.0 and 22.4 microg/ml and the mean IC50 of hematopoietic progenitors (BFU-E, CFU-E and CFU-GM) was 1.8 and 1.7 microg/ml for cisplatin and carboplatin, respectively.


CONCLUSIONS
Carboplatin required a 10 times higher drug concentration than cisplatin to induce a similar degree of growth inhibition on leukemic cells. However, the hematopoietic progenitors responded equally to cisplatin and carboplatin at the same drug concentration. The results suggest that the myelosuppressive activity of carboplatin is greater than its antileukemic effect.
Su
W C
WC
Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan. sunnysu@mail.ncku.edu.tw
Chang
S L
SL
Chen
T Y
TY
Chen
J S
JS
Tsao
C J
CJ
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001853:Bone Marrow / Q000187:drug effects*; D016190:Carboplatin / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000494:pharmacology*; D018922:HL-60 Cells / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D020014:K562 Cells / Q000187:drug effects; D007938:Leukemia / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D006131:Growth Inhibitors; D016190:Carboplatin; D002945:Cisplatin