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Joyce F. Liu, MD, MPH
Joyce F. Liu, MD, MPH
Posted: Wednesday, September 10, 2025
In a multicenter retrospective cohort study published in JAMA Network Open, González Sánchez et al compared paclitaxel-based hyperthermic intraperitoneal chemotherapy (HIPEC) with the standard cisplatin-based regimen in women with advanced ovarian cancer who underwent interval cytoreductive surgery. Drawing on data from Spain’s National Registry of Peritoneal Carcinomatosis, the study evaluated overall survival, disease-free survival, and perioperative morbidity.
Study Details
Eligible study participants were women diagnosed with high-grade stage IIIC or IV serous ovarian carcinoma who had undergone interval cytoreductive surgery with cisplatin- or paclitaxel-based HIPEC. All patients received neoadjuvant and adjuvant chemotherapy per national protocols. The primary endpoints were overall survival and disease-free survival. The secondary endpoint was the rate of complications in the two study arms (with 30-day morbidity assessed using the Clavien-Dindo classification).
From January 2012 to December 2022, 846 patients met inclusion criteria: 325 (38.4%) received cisplatin-based HIPEC and 521 (61.6%) received paclitaxel-based HIPEC. Propensity score matching (1:1) was applied to balance the groups and ensure comparability, yielding two matched groups of 199 patients each.
In the cisplatin arm, HIPEC consisted of cisplatin at 75 to 100 mg/m² in 4 L of dextrose-based peritoneal perfusion for 90 minutes at 42 to 43 °C; in the paclitaxel arm, 120 mg/m² of paclitaxel was perfused for 60 minutes under the same thermal conditions.
Key Results
In the matched cohort, median overall survival was 58 months for cisplatin vs 82 months for paclitaxel, with no statistically significant difference between the groups (hazard ratio [HR] = 0.74, 95% confidence interval [CI] = 0.49–1.13; P = .16). Median disease-free survival was 20 months for cisplatin and 21 months for paclitaxel (HR = 0.95, 95% CI = 0.72–1.25; P = .70). Equivalence analysis demonstrated comparable overall survival during the first 20 months and disease-free survival during the first 15 months posttreatment, with a predefined equivalence margin of 0.1.
The authors highlighted that “HIPEC-paclitaxel was associated with comparable oncologic outcomes as HIPEC-cisplatin, suggesting that it could be a viable alternative,” especially for patients who are elderly, frail, have kidney impairment, or exhibit platinum intolerance.
Perioperative morbidity did not differ significantly between groups (odds ratio = 1.32, 95% CI = 0.99–1.76; P = .06). Paclitaxel-based HIPEC avoids nephrotoxicity associated with cisplatin and does not require sodium thiosulfate for renal protection. It also demonstrates lower systemic absorption due to its high molecular weight, which may contribute to its favorable safety profile.
While the study’s retrospective design imposes limitations, including no available data on BRCA status, the use of a national registry and rigorous propensity score matching strengthened the study’s validity, and the findings reinforce the consideration of paclitaxel-based HIPEC as an evidence-supported substitute for cisplatin in select patients with advanced ovarian cancer.
The authors conclude: “Our study suggests that cisplatin and paclitaxel are [two] safe and effective drugs to be used for HIPEC in [interval cytoreductive surgery] for advanced ovarian cancer. As cisplatin is the preferred drug according to strong evidence, paclitaxel could be a valuable alternative for patients with any contraindication to cisplatin, with similar oncological and perioperative outcomes.”
Disclosure: For full disclosures of the study authors, visit jamanetwork.com.
