Intraperitoneal cisplatin: comparison of antitumor activity and toxicity as a function of solvent saline concentration.
The use of increasing concentrations of NaCl in the solvent during administration of cisplatin is known to decrease nephrotoxicity, but its effect on antitumor activity is less certain. A murine tumor model employing the subrenal capsule assay was used to test the toxicity and antitumor activity of intraperitoneal cisplatin at different doses of the drug using varying concentrations of NaCl in the vehicle of administration. Toxicity (measured by LD50, weight loss, and nephrotoxicity) was significantly lower in mice treated with cisplatin prepared in 4.5% NaCl as compared to cisplatin prepared in distilled water (DW) or 0.9% NaCl. Administration of 4.5% NaCl subcutaneously along with intraperitoneal cisplatin prepared in DW failed to decrease toxicity. Despite lower toxicity, no decrease in antitumor activity could be demonstrated based on increasing concentrations of NaCl in the solvent during intraperitoneal therapy.
Mannel
R S
RS
Department of Obstetrics and Gynecology, University of California, Irvine, Orange 92668.
Stratton
J A
JA
Moran
G
G
Rettenmaier
M A
MA
Liao
S Y
SY
DiSaia
P J
PJ
D000818:Animals; D002945:Cisplatin / Q000008:administration & dosage* / Q000494:pharmacology / Q000633:toxicity; D005260:Female; D007668:Kidney / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D014677:Pharmaceutical Vehicles; D012965:Sodium Chloride / Q000008:administration & dosage*; D013370:Subrenal Capsule Assay
D014677:Pharmaceutical Vehicles; D012965:Sodium Chloride; D002945:Cisplatin