14MO - Safety of cytoreductive surgery with hyperthermic intraperitoneal gemcitabine and systemic dacarbazine for recurrent uterine leiomyosarcoma: Preliminary results of a phase II trial

Background

Uterine leiomyosarcoma (uLMS) is a rare, aggressive gynecologic malignancy affecting 1 in 200,000 women. uLMS frequently recurs within the peritoneal cavity, which may result from tumor rupture or surgical morcellation. Current standard of care includes cytoreductive surgery (CRS) and systemic chemotherapy, although recurrence rates are high. This prospective phase II trial aims to investigate safety and efficacy of heated intraperitoneal chemotherapy (HIPEC) using gemcitabine followed by systemic dacarbazine after optimal CRS.

Methods

Patients with recurrent uLMS in the peritoneum deemed resectable were evaluated for inclusion. Blood was collected for circulating tumor DNA (ctDNA) and correlative studies. Enrolled patients underwent optimal CRS, HIPEC with gemcitabine (1,000 mg/m2 for 60 minutes at 42C), and 6 cycles of systemic dacarbazine. Primary endpoint is progression-free survival; secondary endpoints are safety and quality of life (QOL) outcomes.

Results

To date, 13 patients have been enrolled. Median age is 55 years (range 31-84) and 8 had history of specimen morcellation. Median peritoneal carcinomatosis index (PCI) is 8 (range 5-14), and all patients received complete cytoreduction (CCR 0 or 1). Three women experienced a complication relating to CRS/HIPEC (bladder injury, ureter transection, neutropenia). There were no grade 3 or higher treatment-related adverse events. Median hospital stay is 6 days (range 2-12). Ten patients developed recurrence at median interval of 8 months (range 1-24); all who recurred continued chemotherapy and 8 underwent additional CRS. Twelve patients remain alive with median follow up of 25 months (range 3-31): 8 have no current evidence of disease, and 4 are alive with disease. ctDNA assays were obtained for 10 patients perioperatively and all have correlated with tumor burden and recurrence. QOL scores were stable at 1 month postoperatively, compared to preoperatively.

Conclusions

Preliminary results of our phase II trial suggest that CRS/HIPEC with gemcitabine and adjuvant dacarbazine is safe. Further patient accrual and analysis are needed to evaluate efficacy in preventing peritoneal recurrence.

Clinical trial identification

NCT04727242.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Stanford Cancer Center.

Disclosure

All authors have declared no conflicts of interest.