S J Valle1, J Akhter1, A H Mekkawy1, S Lodh2, K Pillai1, S Badar1, D Glenn2, M Power2, W Liauw3, D L Morris4. 1. Department of Surgery, St George Hospital, Kogarah, NSW, Australia. 2. Department of Radiology, St George Hospital, Kogarah, NSW, Australia. 3. Cancer Care Centre, St George Hospital, Kogarah, NSW, Australia. 4. 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.
Abstract
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.
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.
Authors: Ahmad H Mekkawy; Krishna Pillai; Hyerim Suh; Samina Badar; Javed Akhter; Vahan Képénékian; Kevin Ke; Sarah J Valle; David L Morris Journal: Am J Transl Res Date: 2021-12-15 Impact factor: 4.060
Authors: Lillian Dong; Kevin Ke; Samina Badar; Ahmed H Mekkawy; Javed Akhter; Krishna Pillai; Carly J Carter; David L Morris Journal: Am J Transl Res Date: 2022-05-15 Impact factor: 3.940
Authors: Ahmed H Mekkawy; Krishna Pillai; Samina Badar; Javed Akhter; Kevin Ke; Sarah J Valle; David L Morris Journal: Am J Cancer Res Date: 2021-05-15 Impact factor: 6.166
Authors: Samina Badar; Mohamed Azarkan; Ahmed H Mekkawy; Javed Akhter; Krishna Pillai; Rachida El Mahyaoui; Kevin Ke; Lauren Cavanaugh; David L Morris Journal: Am J Transl Res Date: 2021-05-15 Impact factor: 4.060
Authors: Ashok K Dilly; Brendon D Honick; Robin Frederick; Anuleka Elapavaluru; Sachin Velankar; Hima Makala; T Kevin Hitchens; Lesley M Foley; Jianxia Guo; Jan H Beumer; Lora Heather Rigatti; Yong J Lee; David L Bartlett; Haroon A Choudry Journal: Transl Res Date: 2020-10-22 Impact factor: 7.012
Authors: Satish Sagar; Ashok Kumar Rathinavel; William E Lutz; Lucas R Struble; Surender Khurana; Andy T Schnaubelt; Nitish Kumar Mishra; Chittibabu Guda; Nicholas Y Palermo; Mara J Broadhurst; Tobias Hoffmann; Kenneth W Bayles; St Patrick M Reid; Gloria E O Borgstahl; Prakash Radhakrishnan Journal: Clin Transl Med Date: 2021-02