The addition of sodium thiosulphate to hyperthermic intraperitoneal chemotherapy with cisplatin in ovarian cancer

Kate Glennon,Karen Mulligan,Kirsten Carpenter,Ruth Mooney,Jurgen Mulsow,Orla Mccormack,William Boyd,Tom Walsh,Ruaidhri Mcvey,Claire Thompson,Brid Ryan,Katie Padfield,Patrick Murray,Donal J Brennan

doi:10.1016/j.gore.2021.100796

Abstract

Cisplatin based hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to prolong recurrence free and overall survival of women with ovarian cancer who have responded to neoadjuvant chemotherapy. The aim of this study was to assess the impact of cytoreductive surgery with or without the addition of HIPEC on renal function. MethodThis is a retrospective case-controlled study at a tertiary teaching hospital in Dublin, Ireland. All patients who had interval cytoreductive surgery (CRS) and HIPEC from October 2017 to October 2020 were included. A cohort of patients who had interval CRS without HIPEC were included as a control. Sodium thiosulphate (ST) was added to the HIPEC protocol in 2019. In order to assess the impact of ST as a renal protectant, renal function and post-operative outcomes were compared between the groups. ResultsSixty patients who had interval CRS were included, thirty of whom received cisplatin-based HIPEC. Seven received cisplatin 50 mg/m2 without the addition of ST. Twenty three patients received cisplatin 100 mg/m2 and ST. There were no statistically differences in age, body mass index BMI, American society of anaesthesia score, estimated blood loss or peritoneal cancer index between the cohorts (p > 0.05). The only episode of acute kidney injury (AKI) was within the HIPEC cohort, after cisplatin 50 mg/m2 (without ST) and this was sustained at three months. In contrast, no patients within the CRS cohort or cisplatin 100 mg/m2 that received the addition of ST, sustained a renal injury and all had a creatinine within the normal range at three days post operatively. ConclusionThe renal toxicity associated with cisplatin HIPEC and major abdominal surgery can be minimised with careful preoperative optimisation, intra operative fluid management and attention to renal function. The addition of sodium thiosulphate is a safe and effective method to minimise toxicity and should be added to any cisplatin HIPEC protocol.

Highlights

Chemotherapy combined with cytoreductive surgery has been the mainstay of approach to the treatment of epithelial ovarian cancer (EOC)
From October 2017 to October 2020, prospective data was collected on consecutive patients with EOC who attended for interval cytoreductive surgery (CRS) with or without the addition of hyperthermic intra-operative intra peritoneal chemotherapy (HIPEC)
We explore the incidence of acute kidney injury (AKI) and CKD in a cohort of pa tients undergoing CRS with and without HIPEC

Summary

Introduction

Chemotherapy combined with cytoreductive surgery has been the mainstay of approach to the treatment of epithelial ovarian cancer (EOC). The route of chemotherapy administration in EOC has been the subject of much debate. While intraperitoneal chemotherapy (IP) en hances local drug delivery to the peritoneal surface, it has not been widely adopted due to concerns regarding toxicity issues associated with the use of the intraperitoneal catheter (Jaaback and Johnson, 2006). Historic data demonstrated that adjuvant intraperitoneal chemotherapy was associated with a significant survival benefit (Jaa back and Johnson, 2006; Tewari et al, 2015), recent randomised trials have failed to replicate these findings (Walker et al, 2019). Attention has shifted to the use of hyperthermic intra-operative intra peritoneal chemotherapy (HIPEC) in EOC. In addition to CRS, HIPEC has been the cornerstone of treatment in pseudomyxoma peritonei for the last decade (Sugarbaker et al, 1999; chua et al, 1999)

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