Aditi Bhatt1, Ignace de Hingh2, Kurt Van Der Speeten3, Martin Hubner4, Marcello Deraco5, Naoual Bakrin6, Laurent Villeneuve7, Shigeki Kusamura5, Olivier Glehen8. 1. Department of Surgical Oncology, Zydus Hospital, Ahmedabad, India. 2. Department of Surgical Oncology, Catharina Hospital, Eidhoven, The Netherlands. 3. Department of Surgical Oncology, Zeikenhuis Oost-Limberg, Genk, Belgium. 4. Department of Visceral Surgery, Lausanne University Hospital CHUV, Lausanne, Switzerland. 5. Department of Surgical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 6. Department of Surgical Oncology, Centre Hospitalier Lyon-sud, Lyon, France. 7. Department of Clinical Research, Hospices Civils de Lyon, Centre Hospitalier Lyon-sud, Lyon, France. 8. Department of Surgical Oncology, Centre Hospitalier Lyon-sud, Lyon, France. olivier.glehen@chu-lyon.fr.
Abstract
BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) is performed with a wide variation in methodology, drugs, and other elements vital to the procedure. Adoption of a limited number of regimens could increase the collective experience of peritoneal oncologists, make comparison between studies more meaningful, and lead to a greater acceptance of results from randomized trials. This study aimed to determine the possibility of standardizing HIPEC methodology and regimens and to identify the best method of performing such a standardization. METHODS: A critical review of preclinical and clinical studies evaluating the pharmacokinetic aspects of different HIPEC drugs and drug regimens, the impact of hyperthermia, and the efficacy of various HIPEC regimens as well as studies comparing different regimens was performed. RESULTS: The preclinical and clinical data were limited, and studies comparing different regimens were scarce. Many of the regimens were neither supported by preclinical rationale or data nor validated by a dose-escalating formal phase 1 trial. All the regimens were based on pharmacokinetic data and did not take chemosensitivity of peritoneal metastases into account. Personalized medicine approaches such as patient-derived tumor organoids could offer a solution to this problem, although clinical validation is likely to be challenging. CONCLUSIONS: Apart from randomized trials, more translational research and phases 1 and 2 studies are needed. While waiting for better preclinical and clinical evidence, the best way to minimize heterogeneity is by an expert consensus that aims to identify and define a limited number of regimens for each indication and primary site. The choice of regimen then can be tailored to the patient profile and its expected toxicity and the methodology according regional factors.
BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) is performed with a wide variation in methodology, drugs, and other elements vital to the procedure. Adoption of a limited number of regimens could increase the collective experience of peritoneal oncologists, make comparison between studies more meaningful, and lead to a greater acceptance of results from randomized trials. This study aimed to determine the possibility of standardizing HIPEC methodology and regimens and to identify the best method of performing such a standardization. METHODS: A critical review of preclinical and clinical studies evaluating the pharmacokinetic aspects of different HIPEC drugs and drug regimens, the impact of hyperthermia, and the efficacy of various HIPEC regimens as well as studies comparing different regimens was performed. RESULTS: The preclinical and clinical data were limited, and studies comparing different regimens were scarce. Many of the regimens were neither supported by preclinical rationale or data nor validated by a dose-escalating formal phase 1 trial. All the regimens were based on pharmacokinetic data and did not take chemosensitivity of peritoneal metastases into account. Personalized medicine approaches such as patient-derived tumor organoids could offer a solution to this problem, although clinical validation is likely to be challenging. CONCLUSIONS: Apart from randomized trials, more translational research and phases 1 and 2 studies are needed. While waiting for better preclinical and clinical evidence, the best way to minimize heterogeneity is by an expert consensus that aims to identify and define a limited number of regimens for each indication and primary site. The choice of regimen then can be tailored to the patient profile and its expected toxicity and the methodology according regional factors.
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