Adding Paclitaxel to Cisplatin for HIPEC During Debulking May Improve Outcomes for Advanced Epithelial Ovarian Cancer

In a single-institution study conducted at the Cleveland Clinic, the addition of paclitaxel to cisplatin for hyperthermic intraperitoneal chemotherapy (HIPEC) during interval debulking surgery in women with advanced epithelial ovarian cancer was associated with greater oncologic outcomes versus cisplatin alone, according to a presentation at the Society of Gynecologic Oncology (SGO) Virtual Annual Meeting on Women’s Cancer.¹

The median progression-free survival (PFS) for patients receiving cisplatin alone was 11.0 months (95% CI, 10.5-15.6) versus 22.2 months (95% CI, 15.7-not reached) for cisplatin plus paclitaxel (HR, 0.41; 95% CI, 0.20-0.83; P = .011). Recurrence-free survival rates at 1 year for both groups were 36.7% (95% CI, 18.4%-55.1%) and 82.9% (95% CI, 69.3%-96.6%), respectively.

“The combination of paclitaxel/cisplatin is associated with a significantly improved progression-free survival and 1-year recurrence-free survival compared with cisplatin alone without significantly increased morbidity in patients with optimally cytoreduced stage III and IV ovarian cancer undergoing interval debulking surgery plus HIPEC,” Laura Chambers, DO, who is a fellow in training at the Cleveland Clinic Foundation, said a presentation of the data.

Based on a recent phase 3 trial (NCT00426257), data have shown that HIPEC may improve outcomes in patients with advanced or recurrent ovarian cancer. Compared with interval debulking surgery alone, the addition of HIPEC improved PFS from 10.7 months to 14.2 months, respectively (HR, 0.66; 95% CI, 0.50-0.87; P = .003), and OS from 33.9 months to 45.7 months (HR, 0.67; 95% CI, 0.48-0.94; P = .02).²

The primary objective of the current study was to investigate the PFS and peri-operative outcomes in women with epithelial advanced ovarian cancer undergoing interval debulking surgery with HIPEC of cisplatin with or without paclitaxel.

This institutional review board–approved study examined patients with high-grade stage III or IV ovarian cancer treated between January 1, 2017 to December 21, 2020 that were followed in a prospective HIPEC registry clinic. Patients who were eligible had an ECOG status of 2 or less, well-controlled medical co-morbidities, and had undergone optimal cytoreduction to less than 1 cm of residual disease at the time of surgery. HIPEC treatment selection was nonrandomized and was at the discretion of the primary surgeon.

HIPEC was performed with in-flow and out-flow tubing into the abdomen and connected to a profusion pump, with the laparotomy incision closed to ensure airtight seal. Cisplatin was administered at 100 mg/m² with or without paclitaxel at 135 to 175 mg/m². Total infusion time is 90 minutes, with those on combination chemotherapy receiving sequential paclitaxel for 45 minutes followed by cisplatin.

Of the 146 cases of HIPEC performed from 2009 through 2020, 75 cases were chosen in the described study period who had undergone HIPEC with cisplatin alone (n = 42) or with the addition of paclitaxel (n = 33).

Patient demographics for the cisplatin alone and combination chemotherapy groups were as follows: patients had a median age of 64.7 ± 9.7 years and 62.6 ± 8.5 years, respectively (P = .33); were mostly White at 87.8% and 93.9% (P = .4); had a median body mass index of 27.1 ± 6.6 and 27.6 ± 5.9 (P = .77); and had mostly American Society of Anesthesiologists (ASA) physical status of 3, at 59.5% and 68.8% (P = .6). Patients with stage III disease made up 64.3% of the cisplatin alone group and 78.7% of the cisplatin/paclitaxel group, with the rest having stage IV tumors (P = .17), and the majority of patients in both groups had serous histology (100% and 93.9%, respectively; P = .19). Notably, there were no significant differences between groups in terms of medical comorbidities, hereditary genetics (P = .12), preoperative cancer antigen (CA)–125 (P = .06), or number of neoadjuvant chemotherapy cycles prior to surgery (P = .43).

Intraoperative details for patients revealed that there were no significant differences in residual disease following surgery, with 69.0% having R0 resection in the cisplatin alone group versus 87.9% in the cisplatin/paclitaxel group (P = .08). However, operative time was longer in the cisplatin group, at 6.1 hours (range, 5.1-7.3) versus 5.3 hours (range, 4.5-6.0) for cisplatin/paclitaxel (P = .03). No notable differences were seen when examining blood loss (P = .74), procedures, surgical complexity score (P = .45), intra-operative pressor support (P = .3), or intra-operative blood transfusion (P = .21).

“It is notable that our treatment groups are well matched for their demographics and oncologic characteristics, such as residual disease,” Chambers said.

According to the Accordion Postoperative Severity Classification, there were no significant differences in post-operative outcomes (P = .75). In patients receiving cisplatin alone, no complications were noted in 42.9%, mild in 21.4%, moderate in 23.8%, and severe in 9.5% with 1 death (2.4%) recorded. In the cisplatin/paclitaxel group, corresponding rates were 42.4%, 27.3%, 15.2%, 15.2%, and no deaths (0.0%). No significant differences were noted for readmission (P = .72), reoperation (P = .58), veinous thromboembolism (P = .99), anastomotic leak (P = .58), surgical site infection (P = .99), Ileus (P = .99), or death (P = .99) between groups.

A nonsignificant trend for increased intensive care unit admission was noted with the cisplatin/paclitaxel groups versus the cisplatin alone group, at 24.2% versus 7.1%, receptively (P = .05). No significant differences were noted for acute kidney injury (P = .52), length of stay (P = .5), or time to chemotherapy (P = .83). Patients who were discharged to home (70.7% with cisplatin vs 66.7% with cisplatin/paclitaxel) home health (16.7% vs 27.3%, respectively), and skilled nursing facility (12.2% vs 6.1%) showed no significant differences between groups (P = .33).

Chambers noted that the study had several limitations, primarily being that patients were not randomized, and treatment was chosen at the discretion of the primary surgical oncologists, allowing the potential for selection bias. “Furthermore, our findings are reported from a high-volume center for ovarian cancer care, and therefore may not be generalizable to all patients and sectors,” she continued. “Additionally, small sample size and follow-up duration preclude our assessment of long-term survival.”

Despite the limitation, Chambers noted that this was the first study to compare oncologic outcomes in women with this disease who undergo interval debulking and HIPEC chemotherapy with either cisplatin alone or cisplatin/paclitaxel.

“Although further validation is needed in larger cohorts, the combination of paclitaxel with cisplatin may be considered at the time of interval debulking with HIPEC in selected women with advanced ovarian cancer,” Chambers concluded.

References

1. Chambers LM, Horowitz MP, Gruner M et al. Cisplatin and Paclitaxel is Associated with Improved Progression Free Survival compared to Cisplatin alone during Interval Debulking Surgery with Hyperthermic Intraperitoneal Chemotherapy in Women with Advanced Epithelial Ovarian Cancer. Presented at: Society of Gynecologic Oncology Virtual Annual Meeting on Women’s Cancer; March 19-25, 2021; Virtual.

2. van Driel WJ, Koole SN, Sikorska K, et al. Hyperthermic intraperitoneal chemotherapy in ovarian cancer. N Engl J Med. 2018;378(3):230-240. doi: 10.1056/NEJMoa1708618