Oxaliplatin, a third-generation
platinum compound incorporating
oxalate and
1,2-diaminocyclohexane platinum, has been widely used in
chemotherapy regimens for the treatment of metastatic
colorectal cancer. Because of its wide spectrum of antitumor activity,
oxaliplatin has been applied for the treatment of other
carcinomas. However, the antitumor activity of single-agent
oxaliplatin is insufficient. To increase its antitumor effects, polymeric micellar nanoparticles incorporating
1,2-diaminocyclohexane platinum (NC-4016) have been developed. The present study was designed to evaluate the efficacy of
NC-4016 and its association with
peripheral neuropathy, which is a primary dose-limiting factor in
oxaliplatin therapy. The in vitro antitumor activity of
NC-4016 was investigated using human
carcinoma cell lines. To investigate the antitumor effects of
NC-4016 in vivo, nude mice bearing the human
carcinoma cell line KB were administered
NC-4016 or
oxaliplatin. The in vitro growth-inhibiting effect of
NC-4016 was significantly weaker than that of
oxaliplatin. However, the antitumor efficacy of
NC-4016 was superior to that of
oxaliplatin in vivo. Moreover, we compared the severity of
peripheral neuropathy induced by
oxaliplatin and
NC-4016 in a rat model.
Oxaliplatin,
NC-4016, or 5%
glucose (control) were administered by a single tail vein injection. In the
oxaliplatin-treated rats, neither mechanical nor heat
allodynia was observed during the experimental period, whereas cold
hyperalgesia/
allodynia was observed from day 1 to 7. Conversely, cold
hyperalgesia/
allodynia was not observed in the NC-4016-treated rats. The present study demonstrated that the antitumor efficacy of
NC-4016 was superior to that of
oxaliplatin in a mouse model of human
carcinoma cell line KB. In addition, NC-4016-treated rats did not develop acute
cold hypersensitivity, which is frequently experienced by patients after
oxaliplatin administration.