Alleviation of cisplatin nephrotoxicity: efficacy of local intra-arterial injection concomitant with hemodialysis.
Although cis-diamminedichloroplatinum (cisplatin) is widely used in the treatment of malignant tumors, the dose administered is limited because of side effects such as nephrotoxicity. The plasma levels of non-protein-bound platinum, which can be removed by dialysis, play an important role in the antitumor effects and the appearance of side effects. Selective intra-arterial injection of cisplatin during concomitant hemodialysis (HD) was performed in patients with gynecological malignancies. At a dose of 100 mg, about three times the non-protein-bound platinum excreted in the urine during the same period was removed by HD. The area under the time-concentration curve of plasma total platinum up to 5 h after intra-arterial injection was reduced by 46%. When doses of 200 or 250 mg were administered concomitantly with HD, the maximum plasma levels were suppressed to about the same degree as when 100 mg were injected without concomitant HD. A definite reduction in the incidence of side effects was seen, and a reduction in the severity of nephrotoxicity was also observed when 100 mg were given with HD. No severe side effects were found even when 200 or 250 mg were administered with concomitant HD. The antitumor effects were not reduced or possibly potentiated, but follow-up is still of short duration. These results indicate that chemotherapy with local intra-arterial injections of cisplatin using concomitant HD not only reduces systemic side effects, in particular nephrotoxicity, but also allows for increased doses at the tumor site and can be applied in patients with renal dysfunction.
Yura
T
T
Department of Medicine, Emory University, Atlanta, Ga 30033, USA.
Badr
K F
KF
Yuasa
S
S
Kurose
T
T
Ohkawa
M
M
Hando
T
T
Fukunaga
M
M
Matsuo
H
H
D000117:Acetylglucosamine / Q000652:urine; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D005260:Female; D005833:Genital Neoplasms, Female / Q000188:drug therapy; D006801:Humans; D007269:Injections, Intra-Arterial; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control*; D008875:Middle Aged; D006435:Renal Dialysis; D001613:beta 2-Microglobulin / Q000652:urine
D000970:Antineoplastic Agents; D001613:beta 2-Microglobulin; D002945:Cisplatin; D000117:Acetylglucosamine