Dose-limiting toxicities due to cisplatin chemoradiotherapy after short hydration schemes in comparison with long hydration schemes in head and neck squamou cell carcinoma

Abstract

INTRODUCTION Cisplatin dose-limiting toxicity (CDLT), often due to cisplatin-induced nephrotoxicity, is common during cisplatin-based chemoradiotherapy (CRT) in patients with head and neck squamous cell carcinoma (HNSCC). Currently, different strategies consisting of hydration using different saline infusions and varying timeframes are used to combat cisplatin-induced nephrotoxicity. The aim of this study was to assess whether a short hydration (SH) scheme in comparison with a long hydration (LH) scheme leads to less CDLT, specifically due to nephrotoxicity, in HNSCC patients. MATERIAL AND METHODS In this Dutch multicenter retrospective cohort study, HNSCC patients from the Antoni van Leeuwenhoek (AvL) and Amsterdam University Medical Center, location Vrije Universiteit Medical Center (Amsterdam UMC), who were treated with 40 mg/m2 (Cis40) or 100 mg/m2 (Cis100) cisplatin-based CRT, were included. The AvL administered a LH scheme, whereas the Amsterdam UMC administered a SH scheme. The primary outcome was the incidence of CDLT due to nephrotoxicity. CDLT was defined as any toxicity resulting in dose-reduction of ≥50%, treatment delay of at least four days, or early treatment cessation of cisplatin. Data was collected from patients from January 1st 2020 until July 1st 2022. For each patient data was collected until one month after treatment. Chi-square and Fisher’s exact tests were performed to assess differences in incidence. RESULTS In total, 112 patients (AvL 68 patients versus Amsterdam UMC 44 patients) receiving Cis40 and 100 patients (AvL 23 patients versus Amsterdam UMC 77 patients) receiving Cis100 were included. For patients receiving the Cis100 SH scheme, less CDLT due to nephrotoxicity (n = 9 (39%) versus n = 13 (17%), p = 0.024), less treatment changes (n = 14 (61%) versus n = 29 (38%), p = 0.049), and a higher mean cumulative cisplatin dose (230 mg/m2 ± 55 versus 259 mg/m2 ± 62, p = 0.008) were observed as compared to patients receiving the Cis100 LH scheme. In patients receiving Cis40, no significant differences in CDLT were observed. CONCLUSION The current study demonstrates that the Cis100 SH scheme is associated with less treatment changes due to CDLT, particularly nephrotoxicity, compared to the Cis100 LH scheme. This resulted in a higher cumulative cisplatin dose in patients receiving the SH scheme. Therefore, for HNSCC patients receiving Cis100, the SH scheme is preferable.