Experimental local administration of CDDP to in vitro models of gynecological malignant tumors transplanted into nude mice (compared with medroxyprogesterone acetate orally administered).
In order to develop a new method of administration for CDDP, in vitro models of malignant tumors in the field of gynecology were prepared using two cell lines maintained by the authors, and fundamental experiments on the topical injection of CDDP were carried out. In experimental topical injection of CDDP in tumor-bearing nude mice, the test drug demonstrated an excellent tumor regression effect and an inhibitory effect on tumor growth. In the histopathologic examinations, specific necrosis of tumor cells was observed. It was confirmed that this is a highly safe method, as tissue separation, ulceration, or hemorrhagic lesions attributable to the local administration of CDDP were not observed. In the present study, treatment with oral medroxyprogesterone acetate was also used. At the doses used in this study, however, no inhibitory effect on tumor growth or synergism between medroxyprogesterone acetate and CDDP was observed. Topical injection is an excellent pharmacodynamic method that permits the injection of free platin into the tumor itself or in the boundary area between the tumor and normal tissues, with no loss of the drug, and it is considered a safe and effective mode of local administration. Intra-arterial injection of this drug alone or in conjunction with OK-432 can also be used, even though further studies will be required to determine the optimum dosage and reduce side effects. At present, data are being collected on terminal cancer patients for whom no other therapy is available. In the near future this method of administration is expected to be utilized in the clinical treatment of malignant tumors, be it early tumor or progressive cancer.
Tateyama
I
I
Hashii
K
K
Natsuyama
S
S
Kanto
T
T
Tominaga
T
T
Kamitani
N
N
Mori
T
T
D000284:Administration, Oral; D000287:Administration, Topical; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage*; D005260:Female; D005833:Genital Neoplasms, Female / Q000188:drug therapy*; D008525:Medroxyprogesterone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D017258:Medroxyprogesterone Acetate; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014183:Transplantation, Heterologous
D000970:Antineoplastic Agents; D017258:Medroxyprogesterone Acetate; D008525:Medroxyprogesterone; D002945:Cisplatin