HIPEC in Ovarian Cancer: Paclitaxel or Cisplatin for Heated Intraperitoneal Chemotherapy?

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Why It Matters

Ovarian cancer is diagnosed at an advanced stage in approximately 70% of cases, and overall survival remains low in this group. Adding HIPEC (heated intraperitoneal chemotherapy) to interval cytoreductive surgery — especially in patients with a high tumor burden — is being explored as a way to improve outcomes. However, its efficacy and toxicity profile have been debated for years.

Until now, HIPEC has primarily used cisplatin, while large-scale data on paclitaxel have been limited. The current study, conducted across 27 centers in Spain with 846 patients, is the first large-scale analysis directly comparing the two drugs.

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Study Design — In Brief

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Key Findings

Survival Outcomes

• In the matched cohort:
  • Overall survival: 58 months with cisplatin vs 82 months with paclitaxel (HR = 0.74; p = 0.16 – not statistically significant)
  • Disease-free survival: 20 months with cisplatin vs 21 months with paclitaxel (HR = 0.95; p = 0.70 – not statistically significant)
• Equivalence analysis: Survival was statistically equivalent during the first 20 months (OS) and 15 months (DFS).

Adverse Events and Complications

• Although paclitaxel was administered at a higher dose (120 mg/m² over 60 minutes), complication rates did not differ from cisplatin group.
• Major complication rates were similar (p = 0.06).

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🔬 HIPEC Protocols: Cisplatin vs Paclitaxel

🧪 Cisplatin-Based HIPEC

• Dose: 75–100 mg/m²
• Carrier solution: 4 L dextrose-based perfusion (1.5%)
• Duration: 90 minutes
• Temperature: 42–43 °C
• Technique: Open or closed perfusion
• Renal protection: Sodium thiosulfate used in some centers

Note: Cisplatin forms DNA crosslinks that are enhanced by heat, increasing cytotoxicity—but also raising nephrotoxicity risk, necessitating careful patient selection.

🧪 Paclitaxel-Based HIPEC

• Dose: 120 mg/m²
• Carrier solution: 4 L of dextrose-based perfusion (typically 1.5%)
• Duration: 60 minutes
• Temperature: 42–43 °C
• Technique: Open or closed perfusion
• Renal protection: Not required

Note: Paclitaxel stabilizes microtubules, halting mitosis. Although its thermal synergy is lower than cisplatin, it has high local activity and low systemic toxicity due to limited absorption.

📌 Comparative Table

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💡 Clinical Tips

• Paclitaxel is administered in a shorter time (60 min), potentially reducing overall surgical time.
• Low systemic absorption means lower toxicity.
• Cisplatin may have stronger antitumor effects but carries higher side effect risks.

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Implications of Findings

• Paclitaxel appears to be equivalent to cisplatin in terms of survival.
• There was a 24-month increase in median overall survival favoring paclitaxel, though not statistically significant.
• An equivalence margin of ±10% was predefined.

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📚 What Do the Guidelines Say?

HIPEC is used in some centers for recurrent ovarian cancer — particularly in platinum-sensitive relapse — but international guidelines do not yet recommend it routinely.

🔹 May Be Used in Selected Patients Post-Neoadjuvant Therapy

• Some centers offer HIPEC for good performance, platinum-sensitive relapse patients post-neoadjuvant chemotherapy & cytoreductive surgery.
• However, HIPEC carries a notable increase in toxicity.
• Individualized risk–benefit discussions with patients are advised.
• Some patients may reasonably decline due to the toxicity risk.

🔹 Not Recommended Without Neoadjuvant Therapy

In patients undergoing secondary surgery without neoadjuvant chemotherapy, studies have shown no clear benefit from adding HIPEC.

🔬 Key Randomized Evidence

1. HIPEC and Median OS Benefit (n = 415, 2023)

• Patients with platinum-sensitive relapse were randomized post–six cycles of platinum-based chemo (± bevacizumab) to secondary surgery with or without HIPEC.
• Overall survival: HIPEC: 54 months vs control: 46 months (HR = 0.73; 95% CI: 0.56–0.96)
• ≥ Grade 3 toxicity: HIPEC: 49% vs control: 27%
• Common toxicities:
  • Anemia: 23% vs 14%
  • Hepatotoxicity: 11% vs 9%
  • Electrolyte imbalances: 14% vs 1%
  • Renal failure: 10% vs 1%

2. HIPEC Without Neoadjuvant Chemo (n = 167)

In patients undergoing secondary surgery without prior neoadjuvant chemo:

• PFS: Surgery + HIPEC: 25 months vs Surgery alone: 23 months
• No statistically significant difference.

📌 Summary of Guidelines

• HIPEC is not recommended routinely.
• It may be considered in select platinum-sensitive, post-neoadjuvant patients at experienced centers.
• Due to increased toxicity risk, thorough patient counselling is essential.
• HIPEC should not be presented as a default or necessary option.

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What This Means for Clinical Practice

1. For patients with renal impairment, platinum allergy, or frailty, paclitaxel is a safe HIPEC alternative.
2. Complete cytoreduction (CC-0) should be the surgical goal, and HIPEC should be administered at experienced facilities.
3. Patients must receive comprehensive counseling and post-treatment monitoring.
4. Prospective trials are needed to support wider use of paclitaxel HIPEC.

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Study Limitations

• As a retrospective study, it may involve data gaps and selection bias.
• BRCA and HRD status were not recorded.
• Other long-term treatments affecting overall survival were not accounted for.

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Conclusion

Paclitaxel is a safe alternative to cisplatin in HIPEC, showing similar efficacy and toxicity profiles. It is a reasonable choice for patients intolerant to cisplatin.

Clinical Recommendation: For patients scheduled for interval surgery where cisplatin is risky, paclitaxel HIPEC is a rational and safe option.