The IPLA-OVCA Trial, Intra-Peritoneal Local Anaesthetics in Ovarian Cancer

Summary

Surgery and chemotherapy combined constitute first line treatment in women with advanced ovarian cancer. The aim of surgery apart from staging is cytoreduction, i.e. surgical resection of tumour. Radical resection of all tumour visible by the naked eye followed by adjuvant chemotherapy is associated with best chance of prolonged survival. However, because of tumour dissemination in the peritoneal cavity, radical surgery is often very extensive with surgery in all quadrants of the abdomen and multi-organ resection with substantial risk of postoperative severe complications and subsequent delay in administration of adjuvant chemotherapy. Longer time-interval between surgery to start of adjuvant chemotherapy has been associated with decrease in survival. Surgery presents opportunities not only for eradicating tumours but, paradoxically, also for proliferation and invasion of residual cancer cells. It increases the shedding of malignant cells into the blood and lymphatic circulations, inhibits their apoptosis and potentiates their invasion capacity. Additionally, the immune system, the inflammatory system and the neuroendocrine system react to surgery with important changes, which have been proven to promote progression of cancer. Several anaesthesia-related factors play an important role in perioperative tumorigenesis such as inhalational anaesthetics, opiate analgesics, local anaesthetics and regional anaesthesia, all of which may impact short-term morbidity and long-term mortality. A previous randomized placebo-controlled pilot study suggests that women who receive local anesthetics intraperitoneally preoperatively have a significantly decreased time-interval to initiation of adjuvant chemotherapy. In a prospective, randomised, multi-centre study, we plan to further assess if intraperitoneal local anaesthetics administered perioperatively during 72 h leads to early start of chemotherapy compared to placebo in patients undergoing cytoreductive surgery for FIGO stage III-IV ovarian cancer.

Timeline

Start

2020-08-26

Primary completion

2024-01-10

Completion

2028-08-26

Publications

• Background Hayden JM, Oras J, Block L, Thorn SE, Palmqvist C, Salehi S, Nordstrom JL, Gupta A. Intraperitoneal ropivacaine reduces time interval to initiation of chemotherapy after surgery for advanced ovarian cancer: randomised controlled double-blind pilot study. Br J Anaesth. 2020 May;124(5):562-570. doi: 10.1016/j.bja.2020.01.026. Epub 2020 Mar 13.
• Hasselgren E, Kofoed NG, Falconer H, Bjorne H, Zach D, Hunde D, Johansson H, Asp M, Thorlacius K, Kannisto P, Salehi S. Prospective Assessment of Clinically Relevant Fluid Balance Thresholds Associated With Postoperative Complications in Advanced Ovarian Cancer. Acta Anaesthesiol Scand. 2025 Oct;69(9):e70112. doi: 10.1111/aas.70112.
• Nunez-Rodriguez E, Zhang H, Sah D, Cata JP. Intersection Between Local Anesthetics and Cancer Biology: What Now? Where Are We Going? Adv Biol (Weinh). 2025 Oct;9(10):e00122. doi: 10.1002/adbi.202500122. Epub 2025 Aug 7.
• Gultekin O, Gonzalez-Molina J, Sarhan D, Groes-Kofoed N, Hassan MU, Lehti K, Salehi S. Systemic and tumor-specific inflammatory markers VCAM-1 and ICAM-1 as indicators of extent of surgery and oncologic outcome in advanced ovarian cancer. Transl Oncol. 2025 Sep;59:102462. doi: 10.1016/j.tranon.2025.102462. Epub 2025 Jul 12.
• Hasselgren E, Groes-Kofoed N, Falconer H, Bjorne H, Zach D, Hunde D, Johansson H, Asp M, Kannisto P, Gupta A, Salehi S. Effect of intraperitoneal ropivacaine during and after cytoreductive surgery on time-interval to adjuvant chemotherapy in advanced ovarian cancer: a randomised, double-blind phase III trial. Br J Anaesth. 2025 Mar;134(3):662-670. doi: 10.1016/j.bja.2024.10.015. Epub 2024 Nov 20.

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