What is the recommended dose and administration of sodium thiosulphate (Hyperosmolar sodium thiosulfate) for a patient undergoing Hyperthermic Intraperitoneal Chemotherapy (HIPEC) with oxaliplatin to reduce neurotoxicity?

Sodium Thiosulfate Administration Post-HIPEC with Oxaliplatin

Sodium thiosulfate is NOT recommended for prevention of oxaliplatin-induced neurotoxicity in patients undergoing HIPEC, as there is no established evidence supporting its use in this specific clinical context, and current guidelines do not endorse any pharmacologic agent for oxaliplatin neuropathy prevention. 1

Evidence Base for Sodium Thiosulfate

Established Indications

• Sodium thiosulfate has proven efficacy only for cisplatin-induced ototoxicity in pediatric patients with non-metastatic cancers, administered at 16-20 g/m² IV given 6 hours after cisplatin infusion 1
• The SIOPEL 6 trial demonstrated that 20 g/m² sodium thiosulfate given 6 hours post-cisplatin reduced hearing loss from 63% to 33% (p=0.002) in children with hepatoblastoma without compromising survival 1

Critical Limitation for Oxaliplatin

• No clinical trials have evaluated sodium thiosulfate for oxaliplatin-induced neurotoxicity 1
• The mechanism of platinum-induced neurotoxicity differs between cisplatin and oxaliplatin, making extrapolation of cisplatin data inappropriate 2
• Oxaliplatin causes unique acute cold-triggered dysesthesias and chronic cumulative sensory neuropathy through voltage-gated sodium channel dysfunction, distinct from cisplatin's mechanism 3, 4

ASCO Guideline Position on Oxaliplatin Neuropathy Prevention

No Recommended Agents

• The 2014 ASCO Clinical Practice Guideline explicitly states there is insufficient evidence to recommend any pharmacologic agent for prevention of oxaliplatin-induced peripheral neuropathy 1
• Calcium/magnesium infusions, previously considered, are specifically recommended against based on the negative N08CB trial (353 patients, no reduction in cumulative sensory neurotoxicity) 1

Agents Evaluated Without Recommendation

• Glutathione (GSH) showed mixed results: two small trials (Cascinu 2002, Milla 2009) suggested benefit for oxaliplatin neuropathy, but these were insufficient for guideline endorsement 1
• GSH at 1,500 mg/m² IV over 15 minutes before oxaliplatin reduced grade 3-4 neurotoxicity in one 52-patient trial (0% vs 26%, p=0.01), but larger confirmatory trials are lacking 1
• Importantly, GSH showed no benefit for taxane-based regimens, and ASCO states it is ineffective for paclitaxel/carboplatin neuropathy prevention 5

Evidence-Based Management Strategy for HIPEC Patients

Primary Approach: Dose Modification

• Discontinue oxaliplatin after 3 months of therapy (or cumulative dose ~510-680 mg/m²) if significant neurotoxicity develops (≥grade 2), while continuing other chemotherapy agents 1, 6
• The "stop-and-go" approach from OPTIMOX1 demonstrated decreased neurotoxicity without affecting overall survival in metastatic colorectal cancer 1
• For HIPEC specifically, the intraperitoneal route may alter pharmacokinetics and reduce systemic neurotoxicity compared to IV administration, though data are limited 2

Monitoring Parameters

• Assess for peripheral neuropathy before each oxaliplatin cycle using standardized grading (NCI-CTCAE) 6
• Educate patients about cold avoidance to minimize acute cold-triggered dysesthesias 3, 7
• Monitor cumulative oxaliplatin dose, as chronic neuropathy is highly predictable and dose-dependent (typically occurs at cumulative doses >780-850 mg/m²) 4, 7

Why Sodium Thiosulfate Should Not Be Used

Timing Incompatibility

• Sodium thiosulfate requires administration 6 hours after platinum infusion to avoid chemotherapy interference 1
• HIPEC involves direct intraperitoneal oxaliplatin exposure during surgery with immediate peritoneal lavage, making the 6-hour delay impractical and mechanistically irrelevant 2

Lack of Oxaliplatin-Specific Data

• All sodium thiosulfate trials used cisplatin, not oxaliplatin 1, 8
• The intraperitoneal route in HIPEC fundamentally changes platinum pharmacokinetics compared to IV cisplatin regimens studied with sodium thiosulfate 8

Potential Harm Without Benefit

• High-dose antioxidants like sodium thiosulfate may theoretically protect cancer cells from oxidative damage during active treatment 5
• No sterile pharmaceutical formulations are designed for post-HIPEC administration 5

Clinical Bottom Line

For patients undergoing HIPEC with oxaliplatin, focus on cumulative dose limitation (discontinue after 3 months or at first sign of grade ≥2 neuropathy), cold avoidance education, and close neurotoxicity monitoring rather than unproven pharmacologic prophylaxis. 1, 3, 7 The reversibility of oxaliplatin neuropathy after treatment cessation (unlike cisplatin) makes early recognition and dose modification the most evidence-based strategy. 4, 7