W C Su1, S L Chang, T Y Chen, J S Chen, C J Tsao. 1. Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan. sunnysu@mail.ncku.edu.tw
Abstract
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.
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 leukemicpatients 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.