PMID- 31679953 OWN - NLM STAT- MEDLINE DCOM- 20210420 LR - 20210420 IS - 1532-2157 (Electronic) IS - 0748-7983 (Linking) VI - 47 IP - 1 DP - 2021 Jan TI - A novel treatment of bromelain and acetylcysteine (BromAc) in patients with peritoneal mucinous tumours: A phase I first in man study. PG - 115-122 LID - S0748-7983(19)30913-8 [pii] LID - 10.1016/j.ejso.2019.10.033 [doi] AB - BACKGROUND: Bromelain (Brom) and Acetylcysteine (Ac) have synergistic activity resulting in dissolution of tumour-produced mucin both in vitro and in vivo. The aim of this study was to determine whether treatment of mucinous peritoneal tumour with BromAc can be performed with an acceptable safety profile and to conduct a preliminary assessment of efficacy in a clinical setting. METHODS: Under radiological guidance, a drain was inserted into the tumour mass or intraperitoneally. Each patient could have more than one tumour site treated. Brom 20-60 mg and Ac 1.5-2 g was administered in 5% glucose. At 24 h, the patient was assessed for symptoms including treatment-related adverse events (AEs) and the drain was aspirated. The volume of tumour removed was measured. A repeat dose via the drain was given in most patients. All patients that received at least one dose of BromAc were included in the safety and response analysis. FINDINGS: Between March 2018 and July 2019, 20 patients with mucinous tumours were treated with BromAc. Seventeen (85%) of patients had at least one treatment-emergent AE. The most frequent treatment-related AEs were CRP rise (n = 16, 80%), WCC rise (n = 11, 55%), fever (n = 7, 35%, grade I) and pain (n = 6, 30%, grade II/III). Serious treatment-related AEs accounted for 12.5% of all AEs. There were no anaphylactic reactions. There were no deaths due to treatment-related AEs. An objective response to treatment was seen in 73.2% of treated sites. CONCLUSION: Based on these preliminary results and our preclinical data, injection of BromAc into mucinous tumours had a manageable safety profile. Considerable mucolytic activity was seen by volume of mucin extracted and radiological appearance. These results support further investigation of BromAC for patients with inoperable mucinous tumours and may provide a new and minimally invasive treatment for these patients. CI - Copyright (c) 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved. FAU - Valle, S J AU - Valle SJ AD - Department of Surgery, St George Hospital, Kogarah, NSW, Australia. FAU - Akhter, J AU - Akhter J AD - Department of Surgery, St George Hospital, Kogarah, NSW, Australia. FAU - Mekkawy, A H AU - Mekkawy AH AD - Department of Surgery, St George Hospital, Kogarah, NSW, Australia. FAU - Lodh, S AU - Lodh S AD - Department of Radiology, St George Hospital, Kogarah, NSW, Australia. FAU - Pillai, K AU - Pillai K AD - Department of Surgery, St George Hospital, Kogarah, NSW, Australia. FAU - Badar, S AU - Badar S AD - Department of Surgery, St George Hospital, Kogarah, NSW, Australia. FAU - Glenn, D AU - Glenn D AD - Department of Radiology, St George Hospital, Kogarah, NSW, Australia. FAU - Power, M AU - Power M AD - Department of Radiology, St George Hospital, Kogarah, NSW, Australia. FAU - Liauw, W AU - Liauw W AD - Cancer Care Centre, St George Hospital, Kogarah, NSW, Australia. FAU - Morris, D L AU - Morris DL AD - Department of Surgery, St George Hospital, Kogarah, NSW, Australia; Department of Surgery, University of New South Wales St George Clinical School, Kogarah, NSW, Australia. Electronic address: David.Morris@unsw.edu.au. LA - eng PT - Clinical Trial, Phase I PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20191031 PL - England TA - Eur J Surg Oncol JT - European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology JID - 8504356 RN - 9001-00-7 (Bromelains) RN - WYQ7N0BPYC (Acetylcysteine) SB - IM MH - Acetylcysteine/administration & dosage/*therapeutic use MH - Adenocarcinoma, Mucinous/*drug therapy/secondary MH - Adult MH - Aged MH - Bromelains/administration & dosage/*therapeutic use MH - Drug Therapy, Combination MH - Female MH - Humans MH - Infusions, Parenteral MH - Injections, Intralesional MH - Male MH - Middle Aged MH - Neoplasm Grading MH - Peritoneal Neoplasms/*drug therapy/secondary MH - Radiography, Interventional OTO - NOTNLM OT - Acetylcysteine OT - Bromelain OT - Cytoreductive surgery and intraperitoneal chemotherapy OT - Mucinous peritoneal tumour OT - Mucolytic drug COIS- Declaration of competing interest Professor D.L. Morris is the co-inventor and assignee of the intellectual property and co-owner and director of the sponsor company, Mucpharm Pty Ltd. Ms S.J. Valle is co-owner of Mucpharm Pty Ltd. Dr J. Akhter, Dr K. Pillai are employed by Mucpharm Pty Ltd and co-inventors of the intellectual property. Professor D.L. Morris and the study team guarantees that the conduct of this study is in accordance with protocol, ethics and national and government (hospital) guidelines and regulations. EDAT- 2019/11/05 06:00 MHDA- 2021/04/21 06:00 CRDT- 2019/11/05 06:00 PHST- 2019/09/11 00:00 [received] PHST- 2019/10/25 00:00 [accepted] PHST- 2019/11/05 06:00 [pubmed] PHST- 2021/04/21 06:00 [medline] PHST- 2019/11/05 06:00 [entrez] AID - S0748-7983(19)30913-8 [pii] AID - 10.1016/j.ejso.2019.10.033 [doi] PST - ppublish SO - Eur J Surg Oncol. 2021 Jan;47(1):115-122. doi: 10.1016/j.ejso.2019.10.033. Epub 2019 Oct 31.