Synergy of the combination of nedaplatin with etoposide in murine and human lung carcinoma.
BACKGROUND
The combination of cisplatin (CDDP) and etoposide (ETP) has been shown to be an effective treatment for lung cancer. Nedaplatin (NDP) has been developed as a second generation plainum complex. Because of its superior antitumor activity and lower nephrotoxicity in comparison with CDDP, the antitumor effects of NDP in combination with ETP against murine and human lung cancer was investigated.


METHODS
Lewis murine lung carcinoma, RERF-LC-AI, and Ma44 human lung cancer were used in this study. NDP (1/4 to 1 maximum to related dose; MTD) and CDDP (1/4 to 1 MTD) were administered once and ETP (1/32MTD) was administered daily for five days via the tail vein of mice.


RESULTS
In the mice bearing Lewis lung carcinoma, a combination of NDP and ETP resulted in synergistically enhanced inhibition of tumor growth (Treated/Control ratio; T/C = 0.001) in comparison with either NDP or ETP alone (T/C = 0.12 for NDP, T/C = 0.13 for ETP), and prolonged survival (Increased Life Span; ILS% > or = 172) in comparison with either NDP or ETP alone (ILS% = 65 for NDP, ILS% = 54 for ETP). NDP showed a more potent combination effect with ETP than CDDP did for both growth inhibition and survival. This effect was confirmed in human lung cancer. Although body weight loss was enhanced by the combined treatment, it was tolerable. With regards to myelosuppression, no significant difference between NDP plus ETP and CDDP plus ETP was observed.


CONCLUSIONS
These results suggest the superiority of a combination of NDP with ETP against CDDP with ETP as a clinical therapy for lung cancer.
Uchida
N
N
Discovery Research Laboratories II, Shionogi and Co., Ltd., Osaka, Japan.
Kasai
H
H
Takeda
Y
Y
Maekawa
R
R
Sugita
K
K
Yoshioka
T
T
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001835:Body Weight / Q000187:drug effects; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005047:Etoposide / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D016019:Survival Analysis
D009944:Organoplatinum Compounds; D005047:Etoposide; C053989:nedaplatin