A phase II trial of short-course Hyperthermic IntraPEritoneal Chemotherapy (HIPEC) for high tumor burden ovarian cancer: updated report with preliminary survival outcomes

Abstract

Objectives: To present an updated report with preliminary survival outcomes from our feasibility study.

Methods: This study was a non-randomized, open-label, multi-center, single-arm trial on the safety and efficacy of neoadjuvant chemotherapy (NACT) followed by fast-track cytoreductive surgery (CRS) plus short-course HIPEC (i.e.: 30 min) in advanced ovarian cancer (NCT02249013). HIPEC was performed according to the closed-abdomen technique using a concentration-based regimen of cisplatin (25 mg/m2/L) or cisplatin plus doxorubicin (15mg/L) at 41–43°C. Dextrose perfusate was circulated using the Performer HT device (RAND Srl, Medolla, MO, Italy) at a flow rate of 700ml/min. Primary endpoint was PD9 (i.e.: proportion of patients with disease progression or death occurring within 9 months of interval CRS plus HIPEC) and secondary endpoints were morbidity (mortality and complication rates related to CRS plus HIPEC), time to start adjuvant chemotherapy, length of ICU and hospital stay, QoL over treatment (EORTC QLQ-C30), and ultimately progression-free (PFS) and overall (OS) survivals. Funding sources were from Decit/SCTIE/MS - CNPq/FACEPE/SES-PE (APQ:0187-4.01/13) and FAPE/IMIP.

Results: A total of 15 patients with stage III epithelial malignancies were recruited from our public health system between February 2015 and July 2019 in four Brazilian centers. The median (range) age was 46 years (19–67), with preoperative serum CA125 levels of 737.7U/mL (161.6–6550). The median number of preoperative cycles of IV chemotherapy was 3 (2–4), resulting in PCI scores of 11 (3–18) at the time of interval CRS plus HIPEC performed after a median of 29 days (26–43) from the last neoadjuvant cycle. Time to restarts IV chemotherapy was 39 days (31–74) and fourteen (93.3%) patients completed all the six cycles of IV chemotherapy as planned. Only 1 patient did not start the systemic adjuvant therapy due to poor recovery after surgery. Median operation time was 490 minutes (235–865), with 9 (60%) patients requiring major bowel resection as rectosigmoidectomy (n=8) or partial colectomy (n=1), but with a nil rate of ostomies. Median length of hospital stay was 5 days (3–10), with ICU stay of 1 day (1–5). Four patients experienced no postoperative complications, whereas 5 suffered only minor G1/G2 complications, and 6 suffered major G3 complications, according to the NCI/CTCAE classification. The most common complications were electrolytes imbalance and anemia. Two patients experienced reoperation because of G3 postoperative hemorrhage or peritoneal infection, whereas no deaths were recorded. No significant difference over time in the QLQ-C30 summary scores was observed (p>0.05). With a median follow-up of 32 (18.2–61.2) months, PD9 and median PFS was 6.7% and 18 months, respectively. At this time, median OS was not reached and our 2y- PFS and OS was 30.8% and 92.8%, respectively.

Conclusions: We confirm the preliminary hypothesis of safety and efficacy for our comprehensive approach involving the use of short-course HIPEC in high tumor burden ovarian cancer. Median overall survival is pending to confirm short-course HIPEC at the time of interval CRS as a promising approach in terms of survival outcomes.