[Development of platinum analogues for the treatment of lung cancer].
A number of platinum compounds have been synthesized and screened on the basis of structure-activity strategy. In Japan, clinical trials of three analogues (NK-121, DWA-2114R and 254-S) have been undertaken. NK-121, which have the same leaving group as carboplatin, the dose limiting factor (DLF) was leukopenia, while renal toxicity was extremely mild. DWA-2114R, also with the same leaving group, was less nephrotoxic than CDDP or less marrow toxic than CBDCA. DLF was also leukopenia. Phase II study revealed 29% and 12% response rates for small cell carcinoma (SCLC) and non-small cell carcinoma (NSCLC), respectively. In 254-S which has the same carrier ligand (NH2) as CDDP and CBDCA. DLF was thrombocytopenia with mild nephrotoxicity. Response rates of 41% and 21% were obtained for SCLC and NSCLC, respectively. In a randomized study comparing 254-S plus VDS with CDDP plus VDS, equivalent response rate and milder toxicity were observed for the 254-S group. Since highly active agents other than platinum compounds have been currently evaluated for the cases of lung cancer, preclinical screening for substantially active compounds is essential in developing new platinum analogues.
Nakai
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Dept. of Internal Medicine, Sendai Kosei Hospital, Japan.
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016190:Carboplatin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D018288:Carcinoma, Small Cell / Q000188:drug therapy; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D009944:Organoplatinum Compounds / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C058816:DWA 2114; C055425:NK 121; C053989:nedaplatin; D016190:Carboplatin