10-Year Results of Heated Chemotherapy (HIPEC) in Advanced Ovarian Cancer

Ovarian cancer ranks 8th among cancers in women for both incidence and mortality. Limited treatment options and frequent diagnosis at advanced stages make research into new, effective treatments essential. The phase III OVHIPEC-1 clinical trial examined the long-term benefits of adding hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery (tumor-reducing surgery between treatment phases) in advanced ovarian cancer. This article explores its findings and significance in detail.

HİPEK is a method of administering heated chemotherapy into the abdominal cavity during surgery. HİPEK is the Turkish abbreviation for Hyperthermic IntraPeritoneal Chemotherapy, while the English abbreviation HIPEC stands for Hyperthermic IntraPeritoneal Chemotherapy. Because HIPEC is commonly used in Turkish articles, we use HIPEC throughout the rest of this article.

Interval Cytoreductive Surgery: What Is It, and Why Is It Important?

In ovarian cancer treatment, completely or substantially removing the tumor is generally a main goal. Sometimes, however, disease is so widespread in the abdomen that complete removal at the initial operation is impossible. This is where interval cytoreductive surgery comes in. Performed after other treatments such as chemotherapy, it aims to reduce the tumor further and improve quality of life.

Key Information

• When Is It Performed?: Interval cytoreductive surgery generally follows several chemotherapy cycles. This shrinks the tumor and enables more effective surgery.
• What Is Its Purpose?: Its main purpose is to reduce tumor burden, potentially prolonging life and improving quality of life.
• Who Is It Suitable For?: It is generally suitable for patients with advanced cancer, particularly when the tumor could not be completely removed at the initial operation.
• Risks and Adverse Effects: Like any operation, interval cytoreductive surgery carries risks of complications. Experienced surgeons can generally minimize these risks.

Details of the OVHIPEC-1 Study

• Between 2007 and 2016, 245 patients with stage III ovarian cancer were enrolled from eight HIPEC centers in the Netherlands and Belgium.
• In OVHIPEC-1, not all patients underwent surgery initially. The participants were unsuitable for the initial operation (primary cytoreduction).
• These patients first received neoadjuvant (preoperative, tumor-shrinking) chemotherapy consisting of at least three cycles of carboplatin and paclitaxel. Their disease had not progressed after these cycles. Patients were enrolled if residual tumor was expected to be smaller than 10 mm in diameter during surgery. This criterion was important for selection: patients with residual tumor larger than 10 mm were excluded because this might indicate ineffective treatment. Residual tumor smaller than 10 mm, however, could indicate that neoadjuvant chemotherapy was effective and surgery could remove more tumor tissue.
• After surgery, patients received three additional cycles of carboplatin and paclitaxel, each 3 weeks apart.
• Sodium thiosulfate was given during and after HIPEC to prevent cisplatin-related kidney toxicity.

Study Arms

• 122 patients were randomized to interval cytoreductive surgery plus HIPEC with intraperitoneal cisplatin 100 mg/m²,
• and 123 patients to interval cytoreductive surgery alone.

This approach aimed to reduce tumor burden and increase the effectiveness of subsequent interval cytoreductive surgery.

Key Findings

• Median follow-up was 10.4 years in the surgery/HIPEC group and 10.1 years in the surgery-alone group.
• Median progression-free survival was 14.3 months with surgery/HIPEC versus 10.7 months with surgery alone.
• Median overall survival was 44.9 months with surgery/HIPEC versus 33.3 months with surgery alone.

OVHIPEC-1 and Its Impact on Clinical Practice

Advanced ovarian cancers tend to recur despite current treatments such as chemotherapy, newer drugs including PARP inhibitors , and cytoreductive surgery. OVHIPEC-1 aims to fill this gap and add a new dimension to advanced ovarian cancer treatment.

Contribution to the Literature

• Long-Term Follow-Up: The study evaluates long-term outcomes over 10 years, an important contribution because most studies focus on short- or medium-term results.
• Randomized Controlled Design: Its randomized controlled design increases the reliability of the findings.
• After Neoadjuvant Chemotherapy: The study focuses on patients who received neoadjuvant chemotherapy without disease progression, providing more specific findings for this patient group.

Differences From Earlier Studies

• Adding HIPEC: The study evaluates adding HIPEC to interval cytoreductive surgery, introducing a new treatment component unlike many other studies.
• Multicenter Approach: It was conducted at different HIPEC centers in the Netherlands and Belgium, potentially increasing the generalizability of its results.

Could It Change Clinical Practice?

• Survival Rates: Adding HIPEC significantly improved progression-free and overall survival. This could change clinical practice and encourage wider use of HIPEC.
• Treatment Protocols: If other studies confirm these findings, HIPEC could become standard practice in advanced ovarian cancer treatment.

Conclusion

In conclusion, OVHIPEC-1 may represent an important advance in advanced ovarian cancer treatment and provide a strong basis for reviewing current treatment protocols.