A model for metastatic
skin cancer using
intradermal injection of Walker 256
carcinosarcoma has been developed in the rat. Using this model, antitumor activity of topically applied
doxorubicin and
diaziquone in Vanicream,
Plastibase, and
dimethyl sulfoxide (
DMSO) as vehicles was compared with
intraperitoneal injection of the drugs at the same doses beginning 4 days after injection of
tumor cells.
Doxorubicin applied topically at 0.5 mg/day for 4 days in Vanicream or
Plastibase exhibited no antitumor activity, while i.p. administered
doxorubicin at 0.5 mg/day for 4 days inhibited
tumor growth at day 20 by 66%.
Diaziquone applied topically at 0.1 mg/day for 4 days in Vanicream,
Plastibase, or
DMSO inhibited
tumor growth at day 20 by 66, 86, and 43%, respectively, and cured animals of the skin
tumor at a dose of 0.5 mg/day.
Diaziquone administered i.p. at 0.5 mg/day for 4 days was lethal to rats, and at 0.1 mg/day it produced 93% inhibition of
tumor growth at day 20.
Diaziquone applied topically at 0.1 mg/day for 4 days in
Plastibase cured rats of advanced
tumor when treatment was begun 12 days after injection of
tumor cells. The area under the plasma radioactivity time curve over 5 h for a single 0.64-mg dose of topically applied [ring-14C]
diaziquone in
DMSO was 0.01% that of the same dose of [ring-14C]
diaziquone administered i.p. in non-tumored rats. The decrease in WBC count following topical application of
diaziquone at a dose of 0.1 mg/day for 4 days, compared to the same dose of
diaziquone administered i.p., was 62% in Vanicream, 81% in
Plastibase and 33% in
DMSO. Topical
diaziquone was non-toxic to normal skin in the rat and in the domestic pig. It is concluded that topical application of
diaziquone offers a therapeutic advantage over systemic treatment for metastatic
cancer of the skin.