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

Why Does It Matter?

Ovarian cancer is diagnosed at an advanced stage in approximately 70% of cases, and survival rates in this group remain low. Adding HIPEC (hyperthermic intraperitoneal chemotherapy)to interval (post-neoadjuvant) cytoreductive surgery has attracted attention in the hope of extending survival, particularly in patients with a high tumor burden. However, its efficacy and toxicity profile have long been debated.

Until now, the most commonly used HIPEC drug has been cisplatin , while large-scale data on paclitaxel have been limited. This study, involving 846 patients from 27 centers in Spain, is the first large-scale analysis directly comparing the two drugs.

Study Design—At a Glance

Main Findings

Survival Outcomes

• In the matched group:
  • Overall survival: 58 months with cisplatin vs 82 months with paclitaxel (HR = 0.74; p = 0.16 → not significant)
  • Disease-free survival: 20 months with cisplatin vs 21 months with paclitaxel (HR = 0.95; p = 0.70 → not significant)
• Equivalence analysis: The groups were statistically equivalent in overall survival during the first 20 months and disease-free survival during the first 15 months.

Side Effects and Complications

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

🔬 Cisplatin and Paclitaxel in HIPEC: Administration Details

🧪 Cisplatin-Based HIPEC

• Dose: 75–100 mg/m²
• Diluent: 4 liters of peritoneal perfusion fluid containing 1.5% dextrose
• Administration duration: 90 minutes
• Temperature: 42–43 °C
• Method: Open or closed technique
• Additional protection: Agents that reduce nephrotoxicity, such as sodium thiosulfate, may be added

Note: In a hyperthermic environment, cisplatin cross-links DNA, increasing its cytotoxicity. However, the risk of kidney damage also increases, making patient selection critical.

🧪 Paclitaxel-Based HIPEC

• Dose: 120 mg/m²
• Diluent: 4 liters of dextrose-based peritoneal fluid (usually 1.5%)
• Administration duration: 60 minutes
• Temperature: 42–43 °C
• Method: Open or closed HIPEC technique
• Additional precaution: Kidney-protective measures are not required (unlike cisplatin)

Note: Paclitaxel stops mitosis by stabilizing microtubules. Its thermal synergy is lower than cisplatin's, but its strong local effect and low-toxicity profile offer advantages.

📌 Comparison Table

💡 Clinical Tips

• Paclitaxel is administered over a shorter period (60 min), potentially shortening the operation.
• Its systemic absorption is low, with a lower risk of toxicity.
• Cisplatin may have a stronger antitumor effect, but carries a greater risk of side effects.

What the Findings Mean

• Paclitaxel is equivalent to cisplatin in survival.
• Median overall survival increased by 24 months, but the difference was not statistically significant.
• Equivalence margins were set at ±10.

📚 What Do Guidelines Say About HIPEC?

HIPEC (hyperthermic intraperitoneal chemotherapy)is used in some centers for recurrent ovarian cancer, particularly platinum-sensitive relapse , but international guidelines do not yet recommend it routinely.

🔹 May Be Used With Post-Neoadjuvant Surgery in Selected Patients

• Some centers use HIPEC after neoadjuvant chemotherapy + cytoreductive surgery in patients with good performance status and platinum-sensitive relapse.
• However, HIPEC is clearly stated to carry an increased risk of toxicity .
• An individualized risk–benefit assessment with the patient is recommended.
• Some patients may prefer to decline treatment because of high toxicity.

🔹 Use Without Neoadjuvant Therapy Is Not Recommended

HIPEC has been reported in studies not to benefit patients who have not received neoadjuvant therapy and proceed directly to secondary cytoreductive surgery in this setting .

🔬 Key Randomized Data in the Literature

1. HIPEC and Increased Median Overall Survival (n = 415, 2023)

• 415 women with platinum-sensitive relapse were randomized to HIPEC or control before surgery, following platinum-based chemotherapy (6 cycles, optional bevacizumab).
• Overall survival:
  HIPEC: 54 months – Control: 46 months (HR = 0.73; 95% CI: 0.56–0.96)
• Rate of grade ≥ 3 toxicity:
  HIPEC: 49% – Control: 27%
• Most common side effects:
  • Anemia: 23% vs 14%
  • Hepatotoxicity: 11% vs 9%
  • Electrolyte disturbances: 14% vs 1%
  • Kidney failure: 10% vs 1%

2. HIPEC Without Neoadjuvant Therapy (n = 167)

In patients with platinum-sensitive relapse who had not received neoadjuvant therapy and underwent immediate surgery, 167 patients were evaluated:

• PFS: Surgery + HIPEC: 25 months – Surgery alone: 23 months
• No statistical difference.

📌 Clinical Guideline Recommendation—Summary

• HIPEC is not routinely recommended.
• In selected patients with platinum-sensitive relapse who have received neoadjuvant therapy, it may be used at experienced centers .
• Because of the increased risk of toxicity , patient information and individualized decision-making are essential.
• It should not be presented as a treatment without alternatives.

What Does This Mean in Clinical Practice?

1. Paclitaxel may be a safe alternative for patients with kidney failure, platinum allergy, or frailty.
2. Complete tumor removal (CC-0) should be the goal, and HIPEC should be performed at experienced centers.
3. Information about side effects and follow-up are essential.
4. Prospective studies are needed for broader use of paclitaxel.

Limitations of This Study

• The retrospective design may involve missing data and selection bias.
• BRCA and HRD status were not assessed.
• Other treatments that could affect long-term overall survival were not accounted for.

Conclusion

Paclitaxel is a safe alternative with effects and toxicity similar to cisplatin in HIPEC. It is a reasonable option for patients unable to receive cisplatin.

Clinical Recommendation: If cisplatin poses a risk in a patient scheduled for neoadjuvant surgery, paclitaxel HIPEC is a rational and safe choice.