Synergy of the combination of nedaplatin with etoposide in murine and human lung carcinoma

Abstract

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.

Materials and 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.

Conclusion: These results suggest the superiority of a combination of NDP with ETP against CDDP with ETP as a clinical therapy for lung cancer.