What are the clinical considerations for using carboplatin (Carboplatin) in Hyperthermic Intraperitoneal Chemotherapy (HIPEC)?

Carboplatin HIPEC: Clinical Pearls

Carboplatin is NOT the standard agent for HIPEC and should generally be avoided in favor of cisplatin, which remains the guideline-endorsed choice with proven survival benefits. 1

Agent Selection: Cisplatin Over Carboplatin

• Cisplatin at 75-100 mg/m² is the National Comprehensive Cancer Network-recommended standard for HIPEC in ovarian cancer, based on demonstrated improvements in disease-free survival and overall survival 1
• Carboplatin lacks the robust evidence base that supports cisplatin use in HIPEC, with recent high-quality randomized data showing no benefit over standard treatment 2
• The MSK Team Ovary phase II trial definitively showed that carboplatin HIPEC (800 mg/m²) did not improve progression-free survival (12.3 vs 15.7 months, HR 1.54, P=0.05) or overall survival (52.5 vs 59.7 months) compared to surgery alone 2

If Carboplatin Must Be Used: Dosing and Pharmacokinetics

When cisplatin is contraindicated, carboplatin 800-1000 mg/m² over 90 minutes at 41-43°C represents the most studied regimen, though efficacy remains unproven 3, 4, 2

Pharmacokinetic Profile

• Carboplatin achieves a mean 12-fold higher concentration in perfusate versus plasma (348 µg/mL vs 29 µg/mL) with an intraperitoneal-to-plasma AUC ratio of 12.3 3
• The peritoneal-to-plasma AUC ratio reaches 19.5 at 1000 mg/m², demonstrating favorable local drug delivery 4
• Terminal half-life in perfusate is approximately 104 minutes (range 63-190 minutes), supporting the 90-minute perfusion duration 3
• Large interindividual pharmacokinetic variability exists, making systemic exposure difficult to predict 3

Toxicity Profile and Safety Considerations

Hematologic Toxicity

• Grade 3 neutropenia occurs in approximately 13-20% of patients at 800-1000 mg/m² doses 3, 4
• Grade 4 neutropenia and thrombocytopenia can occur but are typically transient, with only occasional treatment delays required 4
• Hematologic toxicity is generally acceptable and does not compromise ability to deliver standard postoperative platinum-based chemotherapy 5, 4

Renal Considerations

• Carboplatin has significantly lower nephrotoxicity risk compared to cisplatin, which causes AKI in 3.7% of HIPEC patients and permanent renal dysfunction in rare cases 6
• Normal baseline renal function is required before carboplatin HIPEC 1
• Unlike cisplatin, carboplatin does not typically cause significant hypomagnesemia (cisplatin causes hypomagnesemia in 24.5% by day 7 and 30.1% by day 30) 6

Perioperative Safety

• No intraoperative complications or adverse events directly attributable to carboplatin HIPEC have been reported in prospective studies 4, 2
• Grade 1-2 nausea is the most common postoperative toxicity (60% of patients) 4
• Median hospital stay is 5.5 days, comparable to cytoreductive surgery alone 4
• Bowel resection rates may be lower with HIPEC (37% vs 65%, P=0.008), though this finding requires validation 2

Technical Parameters

• Temperature: 41-43°C maintained throughout perfusion 1, 3
• Duration: 90 minutes is standard for carboplatin protocols 1, 3, 4, 2
• Volume: Adequate perfusate volume to ensure complete peritoneal coverage (specific volumes vary by institutional protocol)

Critical Clinical Context

When Carboplatin Might Be Considered

• Patients with pre-existing renal dysfunction where cisplatin is contraindicated 6
• Patients with significant hearing loss or peripheral neuropathy from prior cisplatin exposure
• However, even in these scenarios, the lack of proven efficacy must be weighed against the procedural risks 2

Integration with Systemic Therapy

• Standard neoadjuvant chemotherapy (carboplatin AUC 5-6 + paclitaxel 175 mg/m²) should be administered before interval debulking surgery 1
• A minimum of 6 total cycles of chemotherapy is required, including at least 3 cycles of adjuvant therapy after HIPEC 1
• Carboplatin HIPEC does not compromise delivery of postoperative intravenous platinum-based chemotherapy 5, 4

Key Pitfalls to Avoid

• Do not assume carboplatin HIPEC provides equivalent efficacy to cisplatin HIPEC - the evidence does not support this assumption 2
• Do not use carboplatin HIPEC outside of clinical trials or highly selected cases where cisplatin is contraindicated 1, 2
• Do not proceed with HIPEC if complete cytoreduction cannot be achieved, as suboptimal debulking negates any potential benefit 1
• Do not use HIPEC after primary debulking surgery - it should only be considered after neoadjuvant chemotherapy and interval debulking 1
• Do not underestimate the large interindividual pharmacokinetic variability, which makes predicting systemic exposure challenging 3

Alternative Considerations for Peritoneal Disease

• For gastric cancer with peritoneal metastases, HIPEC is not recommended for routine clinical practice outside of trials, despite some positive signals in selected populations 7
• Catheter-based intraperitoneal chemotherapy with taxanes represents a less invasive alternative to HIPEC, though evidence remains limited 7
• Standard systemic chemotherapy remains the backbone of treatment for peritoneal metastases across tumor types 7