Association between Area under the Curve Estimated from Carboplatin Dose and Incidence of Severe Thrombocytopenia in Patients with Non-Hodgkin’s Lymphoma on DeVIC Therapy

Umehara, Kengo; Takada, Shinya; Yama, Kaori; Yamagishi, Kayo; Ebata, Ko; Sakai, Toshiya; Kobayashi, Michiya; Sato, Hideki; Mino, Kozo; Fujimoto, Kastuya

doi:10.31557/APJCP.2023.24.6.1963

Association between Area under the Curve Estimated from Carboplatin Dose and Incidence of Severe Thrombocytopenia in Patients with Non-Hodgkin’s Lymphoma on DeVIC Therapy

Document Type : Research Articles

Authors

¹ Department of Pharmacy, National Hospital Organization Hokkaido Cancer Center; 2-3-54 Kikusui 4, Shiroishi-ku, Sapporo, Hokkaido, Japan.

² Division of Clinical Pharmacy, Department of Pharmacy, Faculty of Pharmaceutical Sciences, Hokkaido University of Science, 15-4-1 Maeda 7, Teine-ku, Sapporo, Hokkaido, Japan.

³ Department of Hematology, National Hospital Organization Hokkaido Cancer Center; 2-3-54 Kikusui 4, Shiroishi-ku, Sapporo, Hokkaido, Japan.

⁴ Division of Pharmaceutics (Clinical Pharmaceutics), School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, 1757 Kanazawa, Tobetsucho, Ishikari-gun, Hokkaido, Japan.

10.31557/APJCP.2023.24.6.1963

Abstract

Background: The degrees of adverse effects with carboplatin (CBDCA) are influenced by interindividual differences in the area under the curve (AUC), whereas renal function is not considered in the CBDCA dose design for dexamethasone, etoposide, ifosfamide, and CBDCA (DeVIC) therapy. We conducted this study to evaluate the association between the AUC and incidence of severe thrombocytopenia in patients treated with DeVIC with or without rituximab (DeVIC ± R). Methods: We retrospectively analyzed clinical data for 36 patients with non-Hodgkin’s lymphoma who received DeVIC ± R between May 2013 and January 2021 at the National Hospital Organization Hokkaido Cancer Center. The AUC of CBDCA (AUC_actual) was calculated backward using a variant of the Calvert formula. Results: The median AUC_actual was 4.6 (interquartile range: 4.3–5.3) min mg/mL and AUC_actual was negatively correlated with the nadir platelet count (r = -0.45; P < 0.01). Multivariate analysis showed that AUC_actual ≥ 4.3 versus < 4.3 was an independent factor predictive of severe thrombocytopenia (odds ratio: 19.3, and 95% confidence interval: 1.45–258; P = 0.02). Conclusion: This study suggests that the CBDCA dosing design considering renal function can reduce the risk of severe thrombocytopenia in DeVIC ± R therapy.

Keywords

Main Subjects