nk-121 and Ovarian-Neoplasms

New cisplatinum derivatives of 254-S, DWA2114R and NK121 developed in Japan were reviewed. These three compounds have less nephrotoxicity and nausea/vomiting than cisplatinum, but have more myelotoxicity. 254-S showed activities against carcinomas of the head and neck, lung, esophagus, urinary tract, prostate, testis, ovary and cervix. DWA2114R showed activities against carcinoma of the ovary, prostate, testis and breast. NK121 is under phase II study. A randomized controlled study of 254-S for non-small-cell lung cancer and DWA2114R for ovarian cancer was performed compared to cisplatinum. The antitumor activity of these compounds was not different from cisplatinum, however the hydration was much less than cisplatinum. These cisplatinum derivatives of 254-S and DWA2114R were thought to be useful for QOL of the patients treated with cisplatinum compound.

Topics: Adult; Aged; Antineoplastic Agents; Carboplatin; Carcinoma, Non-Small-Cell Lung; Cisplatin; Female; Humans; Lung Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Ovarian Neoplasms; Prostatic Neoplasms; Testicular Neoplasms

New cisplatinum derivatives of 254-S, DWA2114R and NK121 developed in Japan were reviewed. These three compounds have less nephrotoxicity and nausea/vomiting than cisplatinum, but have more myelotoxicity. 254-S showed activities against carcinomas of the head and neck, lung, esophagus, urinary tract, prostate, testis, ovary and cervix. DWA2114R showed activities against carcinoma of the ovary, prostate, testis and breast. NK121 is under phase II study. A randomized controlled study of 254-S for non-small-cell lung cancer and DWA2114R for ovarian cancer was performed compared to cisplatinum. The antitumor activity of these compounds was not different from cisplatinum, however the hydration was much less than cisplatinum. These cisplatinum derivatives of 254-S and DWA2114R were thought to be useful for QOL of the patients treated with cisplatinum compound.

Topics: Adult; Aged; Antineoplastic Agents; Carboplatin; Carcinoma, Non-Small-Cell Lung; Cisplatin; Female; Humans; Lung Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Ovarian Neoplasms; Prostatic Neoplasms; Testicular Neoplasms

The clinical efficacy of cisplatin-based chemotherapy for ovarian cancer is frequently compromised by drug resistance or dose-limiting renal and neurologic toxicities. CI-973 (NK-121), a 2-methyl-1,4-butanediamine analogue of carboplatin, has shown little nephro- and neuro-toxicity in pre-clinical model systems and in phase-I trials. Its in vitro spectrum of activity against ovarian cancer cell lines has not been previously characterized. The in vitro activities of CI-973, cisplatin, carboplatin and tetraplatin were compared in several platinum-sensitive and -resistant human ovarian carcinoma cell lines. Cytotoxicity was assessed by inhibition of clonogenic survival in soft agar with continuous drug exposure. On a molar basis, cisplatin and tetraplatin were the most potent analogues, while carboplatin was consistently less potent. Cisplatin, carboplatin and CI-973 elicited a very similar response pattern by Spearman rank correlation, distinct from that seen with tetraplatin. The magnitude of resistance to CI-973 was comparable to cisplatin in 5 cell lines but was substantially lower in the highly cisplatin-resistant 2780-CP70 and OVCAR-10 cell lines. These results suggest that CI-973 and tetraplatin may have potential utility in some cases of cisplatin-resistant ovarian cancer. In addition, our data are consistent with the existence of at least 2 platinum-resistance phenotypes--one with moderate levels of resistance to cisplatin, carboplatin and CI-973 but highly resistant to tetraplatin, the other highly resistant to cisplatin and carboplatin but only partially cross-resistant with tetraplatin and CI-973. The recognition of different resistance phenotypes may facilitate the study of cellular resistance mechanisms to cisplatin and newer platinum analogues.

Topics: Antineoplastic Agents; Carboplatin; Cell Survival; Cisplatin; Drug Resistance; Female; Humans; Organoplatinum Compounds; Ovarian Neoplasms; Tumor Cells, Cultured; Tumor Stem Cell Assay

In the present study, comparison of the therapeutic effects of CDDP and the analogues (CBDCA, 254S, DWA2114R and NK121) on human gynecological carcinomas transplanted into nude mice (uterine cervical cancer; UZ-1-N, endometrial cancer; UE-1-N, ovarian cancer; OCl-1-N, OS-4-N and OS-8-N) was made. CDDP (5 mg/kg), CBDCA (50 mg/kg), 254S (25 mg/kg), DWA (50 mg/kg) and NK121 (18 mg/kg) were administered intraperitoneally every four days at three doses. Simultaneously the tumor size and the body weight were measured and the peripheral WBC and BUN were examined. The results were as follows: 1) The administration of 254S caused a marked inhibition of the tumor growth against all xenografts into nude mice. 2) CDDP and CDDP analogues except 254S were not effective against UE-1-N, but in this xenograft antitumor activity of 254S was remarkable. 3) With 254S, there were a decrease in body weight and the peripheral leukopenia and the elevation of BUN level were more severe. Although 254S has severe side effects, 254S is seemed to be recommendable for the treatment of gynecological malignancies.

Topics: Animals; Antineoplastic Agents; Carboplatin; Cisplatin; Female; Humans; Mice; Mice, Nude; Neoplasm Transplantation; Organoplatinum Compounds; Ovarian Neoplasms; Prognosis; Transplantation, Heterologous; Uterine Neoplasms

The therapeutic effect of cis-1, 1-cyclobutane dicarboxylato-(2R)-2-methyl-1,4-butane diamine platinum (II) (NK 121) on 3 human yolk sac tumors of the ovary (YST-1, YST-2 and YST-3), which were transplanted into nude mice, was compared with that of cisplatin (CDDP). While tumors YST-2 and YST-3 exhibited a broad comparable sensitivity to CDDP and NK 121, YST-1 was substantially more sensitive to CDDP than NK 121. A significant weight loss was noted in the non-tumor bearing nude mice treated with CDDP, as compared with the loss in both control and NK 121-treated groups. NK 121 showed a good antitumor activity without showing severe toxicities.

Topics: Animals; Antineoplastic Agents; Carboplatin; Female; Humans; Mesonephroma; Mice; Mice, Nude; Neoplasm Transplantation; Organoplatinum Compounds; Ovarian Neoplasms