Can oxaliplatin be used for hyperthermic intraperitoneal chemotherapy (HIPEC) in adult patients with peritoneal carcinomatosis from colorectal, appendiceal, or gastric cancer who have adequate renal function (creatinine clearance >60 mL/min) and no severe peripheral neuropathy?

Can Oxaliplatin Be Used for HIPEC?

Yes, oxaliplatin is one of the most commonly used agents for HIPEC and is specifically recommended in multiple clinical contexts, though recent high-quality evidence from the PRODIGE 7 trial questions its survival benefit in colorectal peritoneal metastases. 1, 2

Evidence-Based Recommendations by Cancer Type

Colorectal Cancer

• ASCO and ESMO guidelines (2023-2025) recommend AGAINST adding oxaliplatin-based HIPEC to cytoreductive surgery (CRS) for colorectal peritoneal metastases, based on the PRODIGE 7 trial showing no overall survival benefit (HR 1.00; 95% CI 0.63-1.58) and significantly increased late complications (RR 1.69; 95% CI 1.03-2.77). 2
• The recommended approach is complete CRS plus systemic chemotherapy without HIPEC for appropriately selected patients with isolated peritoneal disease. 2, 3
• Critical caveat: Despite guideline recommendations against HIPEC, oxaliplatin remains technically feasible and was historically used at doses of 200-460 mg/m² for colorectal peritoneal carcinomatosis. 1, 4, 5, 6, 7

Gastric Cancer

• Oxaliplatin is commonly used for HIPEC in gastric cancer, typically at 460 mg/m² in 2 L/m² of 5% dextrose for 30 minutes at 41-42°C. 1, 8
• The 2022 Journal of Clinical Oncology guidelines note that oxaliplatin (along with mitomycin and cisplatin) is among the most commonly used agents for HIPEC in gastric cancer peritoneal metastases. 1
• HIPEC with oxaliplatin may reduce peritoneal recurrence rates (risk ratio 0.63) in patients with advanced gastric cancer without gross peritoneal metastases, though it increases postoperative complications, particularly renal dysfunction. 1
• The ongoing GASTRICHIP trial (NCT01882933) is evaluating adjuvant HIPEC with oxaliplatin in locally advanced gastric cancer patients. 1

Appendiceal Cancer

• Oxaliplatin can be used for HIPEC in appendiceal mucinous neoplasms, though specific dosing protocols vary by institution. 9
• The National Comprehensive Cancer Network recommends referral to specialized CRS-HIPEC centers for patients with limited peritoneal disease (PCI <20-25). 9
• Important warning: Treatment-related mortality is 5.2-8% and grade 3-4 complications occur in 42.9-65% of patients, with renal toxicity (creatinine elevation) occurring in 15% with HIPEC. 9

Technical Specifications for Oxaliplatin HIPEC

Dosing Protocols

• Standard dose: 460 mg/m² in 2 L/m² of 5% dextrose solution for 30 minutes at 42-44°C (established through pharmacokinetic studies). 5, 6
• Alternative dose: 200 mg/m² for 2-hour perfusion at 40°C (maximum tolerated dose in phase I trials). 7
• Combination regimen: 360 mg/m² oxaliplatin combined with 360 mg/m² irinotecan (for selected protocols). 6
• Volume consideration: Increasing instillate volume from 2 L/m² to 2.5 L/m² dramatically decreases oxaliplatin concentration and absorption—avoid this. 5

Pharmacokinetic Advantages

• Peritoneal oxaliplatin concentration is 25-fold higher than plasma concentration at the 460 mg/m² dose level. 5
• Intratumoral oxaliplatin penetration is high, 17.8-fold higher than non-bathed tissues. 5
• Half the oxaliplatin dose is absorbed systemically within 30 minutes at all dose levels. 5

Critical Safety Considerations

Renal Function Requirements

• Adequate renal function (creatinine clearance >60 mL/min) is essential given the significant risk of renal dysfunction with oxaliplatin-based HIPEC. 1, 9
• Renal toxicity is specifically highlighted as a major complication in gastric cancer HIPEC protocols. 1

Neuropathy Concerns

• Patients with pre-existing severe peripheral neuropathy should be excluded, as oxaliplatin causes cumulative peripheral sensory neuropathy. 1
• Grade 3 neuropathy occurs in 10-20% of patients receiving cumulative oxaliplatin doses of 750-850 mg/m² systemically; intraperitoneal administration may have different toxicity profiles. 1

Comparative Toxicity

• When compared to mitomycin C for colorectal HIPEC, oxaliplatin shows lower rates of neutropenia/leukopenia (0% vs 26.8%, P<0.001) and less intraoperative blood loss. 4
• However, no clear survival benefit was demonstrated between oxaliplatin and mitomycin C in comparative studies. 4

Patient Selection Algorithm

For Colorectal Cancer:

1. Confirm isolated peritoneal metastases without extraperitoneal disease
2. Assess feasibility of complete macroscopic cytoreduction (CC-0)
3. Proceed with CRS plus systemic chemotherapy WITHOUT oxaliplatin HIPEC (per ASCO/ESMO 2023-2025 guidelines) 2, 3
4. Consider HIPEC only within clinical trials

For Gastric Cancer:

1. Confirm limited peritoneal carcinomatosis (PCI <6) or tumor-positive cytology without macroscopic disease
2. Verify creatinine clearance >60 mL/min
3. Assess absence of severe peripheral neuropathy
4. Proceed with CRS plus oxaliplatin HIPEC at 460 mg/m² for 30 minutes at specialized centers 1, 5
5. Consider enrollment in GASTRICHIP trial if eligible

For Appendiceal Cancer:

1. Confirm PCI <20-25 and ECOG 0-1
2. Verify no extraperitoneal metastases
3. Assess feasibility of complete cytoreduction
4. Refer to specialized CRS-HIPEC center for evaluation 9

Common Pitfalls to Avoid

• Do not use oxaliplatin HIPEC for colorectal peritoneal metastases outside clinical trials—the PRODIGE 7 trial definitively showed no benefit with increased harm. 2
• Do not increase perfusate volume beyond 2 L/m²—this dramatically reduces drug concentration and efficacy. 5
• Do not proceed without confirming adequate renal function—renal dysfunction is a major complication. 1, 9
• Do not perform HIPEC outside specialized centers with substantial CRS experience—mortality rates are 5.2-8% even in experienced hands. 9