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sodium thiosulfate inca ovary pt post op

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"sodium thiosulfate" AND "calciphylaxis"

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sodium thiosulfate INCA ovarian cancer post-operative cisplatin

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https://pmc.ncbi.nlm.nih.gov/articles/PMC7941151

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"sodium thiosulfate" AND cisplatin AND "ovarian cancer"

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PMID: 37561343

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PMID: 35812006

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Sodium Thiosulfate (STS) in Ovarian Cancer Post-Operative HIPEC

Context

In ovarian cancer, HIPEC (Hyperthermic Intraperitoneal Chemotherapy) - sometimes called INCA (Intraperitoneal Cisplatin-based Chemotherapy) - is performed after complete cytoreductive surgery (CRS). Cisplatin is the chemotherapy of choice for this indication. However, cisplatin carries significant nephrotoxicity risk, and sodium thiosulfate is used as a nephroprotective agent in this setting.

Why Cisplatin Causes Nephrotoxicity in HIPEC

  • Intraperitoneally administered cisplatin remains in the bloodstream for ~5 days after administration
  • As cisplatin accumulates in the kidneys, AKI can develop several days post-operatively (often days 3-9 post-op)
  • HIPEC itself carries added nephrotoxicity risk from intraoperative hypotension due to venous capacitance
  • The result is cisplatin-induced AKI that is more severe and prolonged than with standard IV administration

Role of Sodium Thiosulfate (STS)

Mechanism: STS binds and inactivates free cisplatin in the systemic circulation and kidneys. It:
  1. Prevents cisplatin-DNA adduct formation in renal proximal tubule cells
  2. Protects against cisplatin-induced mitochondrial damage in renal tubular cells
  3. Acts as an antioxidant, neutralizing reactive oxygen species generated by cisplatin
This renal protection is possible because the intraperitoneal cisplatin has already been absorbed by tumor tissue, so systemic neutralization via STS does not significantly compromise antitumor efficacy.

Clinical Use During HIPEC (Prophylactic)

Per the 2022 PSOGI International Consensus (Bhatt et al., 2023 - Ann Surg Oncol):
  • Nephroprotection with sodium thiosulfate should be used for cisplatin HIPEC (strong consensus)
  • Cisplatin 100 mg/m² (OVHIPEC-1 regimen) is the recommended HIPEC regimen for epithelial ovarian cancer
  • HIPEC is performed for a minimum of 60 minutes at ≥41°C intraabdominal temperature
  • STS is given intravenously concurrent with or after cisplatin infusion
As stated in the Sabiston Textbook of Surgery: "Nephroprotection with sodium thiosulfate, given intravenously, is considered when cisplatin is used." (Sabiston, HIPEC chapter)

Post-Operative "Rescue" Use (Delayed STS)

A 2021 case report (Patel et al., PMC7941151) described a novel use: delayed STS administration on post-op day 7 for rescue of established cisplatin nephrotoxicity following HIPEC:
  • Patient developed progressive AKI post-HIPEC (creatinine rose to 4.4 mg/dL by POD 9)
  • STS given at 12 g/m² IV over 6 hours on POD 7
  • Creatinine steadily declined after treatment; at discharge (POD 12), creatinine was 3.24 mg/dL with improving GFR
  • At 6-week follow-up, creatinine had returned to near-baseline
  • This suggests STS may have utility as a rescue agent even days after cisplatin infusion, not just as prophylaxis

Key Side Effect: Hypernatremia

A 2022 retrospective study (Alonso et al., PMID 35812006) of cisplatin-HIPEC patients (72.7% ovarian cancer) found:
  • 100% incidence of transient hypernatremia (sodium >145 mmol/L) with STS use
  • All cases were transient with no clinical sequelae
  • AKI rate was 36.4% despite STS (classified as risk/failure by RIFLE criteria); no long-term renal impairment
  • STS is considered safe in this context, but sodium monitoring post-HIPEC is warranted

Does STS Protect the Ovarian Reserve?

A separate 2024 study (So et al., PMC11017129) investigated whether STS protects the ovarian reserve (relevant in younger patients receiving cisplatin):
  • Conclusion: STS does NOT protect ovarian reserve from cisplatin-induced gonadotoxicity - oocyte/primordial follicle depletion occurs regardless of STS use
  • This is distinct from its renal and ototoxicity protection

Summary Table

ParameterDetail
IndicationCisplatin-based HIPEC in ovarian cancer
Dose (prophylactic)9-12 g/m² IV over 6 hours, given concurrent with or after cisplatin
Dose (rescue/delayed)12 g/m² IV over 6 hours (case report, POD 7)
MechanismBinds/neutralizes cisplatin in systemic circulation; antioxidant; mitochondrial protection
Primary benefitNephroprotection (reduces cisplatin-induced AKI)
AllowsHigher cisplatin doses during HIPEC
Key side effectTransient hypernatremia (100% incidence, usually self-limiting)
Does NOT protectOvarian reserve from cisplatin gonadotoxicity
Guideline statusRecommended by 2022 PSOGI Consensus for cisplatin HIPEC
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