Establishment of nedaplatin safety dose formula based on renal function for combination chemotherapy with nedaplatin and 5-fluorouracil in patients with esophageal cancer

Abstract

Background: It is known that the area under the plasma concentration curve of nedaplatin (AUC_NDP) is associated with the relative reduction ratio of platelets and that the AUC_NDP is based on nedaplatin dose normalized by creatinine clearance (CrCL) (AUC_dose/CrCL). Based on these relationships, in this retrospective study, we aimed to determine the unestablished dose_NDP safe for patients with impaired renal function who received an initial combination chemotherapy with nedaplatin and 5-fluorouracil.

Methods: We performed a retrospective cohort analysis of consecutive patients with esophageal cancer who received an initial combination chemotherapy with ≤ 90 mg m^-2 day^-1 of nedaplatin on day 1 and 800 mg m^-2 day^-1 of 5-fluorouracil on days 1-5. AUC_dose/CrCL was estimated using the formula, 3.2134 × dose_NDP/CrCL + 4.4185. Data obtained during the first 28 days following nedaplatin administration were analyzed to compare AUC_dose/CrCL between the patients with and without grade ≥ 3 thrombocytopenia. Receiver-operating characteristic (ROC) curve analysis was performed to determine the optimal AUC_dose/CrCL cutoff value.

Results: Of the 136 patients included in this study, 8 (5.9%) presented with grade ≥ 3 thrombocytopenia. There were statistically significant differences in the AUC_dose/CrCL between the patients with and those without grade ≥ 3 thrombocytopenia (11.79 vs. 10.09 µg h^-1 mL^-1; P = 0.00828). We found that the appropriate cutoff value for the AUC_dose/CrCL using the ROC curve was 10.945 µg h^-1 mL^-1.

Conclusions: Our results indicate that safe dose_NDP should be estimated to satisfy the following formula: Dose_NDP (mg) < CrCL × 2.031.

Keywords: Creatinine clearance; Esophageal cancer; Impaired renal function; Ishibashi’s formula; Nedaplatin; Thrombocytopenia.