Dumont, F.

Eveno, C.

Glehen, O.

Hübner, M.

Sgarbura, O.

Taibi, A.

English

Taibi, Abdelkader

Hübner, Martin

Eveno, Clarisse

Dumont, Frederic

Glehen, Olivier

Sgarbura, Olivia

HAL: Hyper Article en Ligne

ASO Author Reflections: Is There Still a Role for Intraperitoneal Oxaliplatin for Colorectal Peritoneal Metastases?

HAL-UNILIM

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Serveur académique lausannois

ASO AUTHOR REFLECTIONSASO Author Reflections: Is There Still a Role for IntraperitonealOxaliplatin for Colorectal Peritoneal Metastases?Abdelkader Taibi, MD, PhD1,2 , Martin Hübner, MD, PhD3, Clarisse Eveno, MD, PhD4,5,Frederic Dumont, MD, PhD6, Olivier Glehen, MD, PhD7, and Olivia Sgarbura, MD, PhD8,91Digestive Surgery Department, Dupuytren Limoges University Hospital, Limoges, France; 2CNRS, XLIM, UMR 7252,University Limoges, Limoges, France; 3Department of Visceral Surgery, Lausanne University Hospital (CHUV),University of Lausanne (UNIL), Lausanne, Switzerland; 4Department of Digestive and Oncological Surgery, ClaudeHuriez University Hospital, Lille, France; 5UMR-S1277 - CANTHER Laboratory ‘‘Cancer Heterogeneity, Plasticity andResistance to Therapies’’, Lille, France; 6Department of Surgical Oncology, Institut de Cancérologie de l’Ouest, SaintHerblain, France; 7Department of General Surgery and Surgical Oncology, Lyon Sud University Hospital, Pierre Benite,France; 8Department of Surgical Oncology, Cancer Institute of Montpellier, University of Montpellier, Montpellier,France; 9IRCM, Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Institut régional du Cancer deMontpellier, Université de Montpellier, Montpellier, FrancePASTSince the development of oxaliplatin (Ox) as a potentintravenous (IV) cytotoxic drug for metastatic colorectalcancer in the late 1990s, there were high hopes for itsefficacy in the clinical setting of peritoneal metastases(PM). Its benefit was mostly proved in combination withIV fluorouracil (5-FU).1 Oxaliplatin was rapidly adopted asan intraperitoneal (IP) drug, as the molecule fulfilled at thattime all conditions to be an ideal antineoplastic agent for IPtherapy, including documented activity against the malig-nant disease to be treated. During the same period,hyperthermic intraperitoneal chemotherapy (HIPEC)gained popularity for PM of colorectal origin. Severalstudies suggested increased local absorption of IP oxali-platin when combined with 5-FU systemically. Thus, high-dose oxaliplatin (Ox) associated with intravenous 5-FUquickly became the regimen of choice after cytoreductivesurgery (CRS).2PRESENTThe recently published PRODIGE7 trial randomizedpatients with colorectal PM after CRS to high-dose Ox-based HIPEC and IV 5-FU versus no HIPEC. The majorityof patients received perioperative systemic chemotherapyin addition. Equivalent overall survival results werereported for the two arms (41.7 vs. 41.2 months), but themorbidity rate was significantly higher in the HIPEC groupat 60 days (26% vs. 15%).3 Possible causes of failure of thehigh-dose Ox-based HIPEC are mainly of a pharmacoki-netic nature, namely single-shot administration and shortduration. Thus, it cannot be inferred from PRODIGE7 thatOx is the wrong drug for any IP modality.3 In parallel,pressurized intraperitoneal aerosol chemotherapy (PIPAC)was developed as a new technique for repeatedly deliveringcytotoxic agents in the clinical setting of unre-sectable peritoneal disease. Oxaliplatin-based PIPACbecame a valuable option for patients with unre-sectable PM of colorectal origin who had previouslyundergone standard lines of treatment.4 However, in thedevelopment of this new modality, the association ofoxaliplatin-based PIPAC with IV 5-FU was not thoroughlystudied until recently.4,5 Society of Surgical Oncology 2022First Received: 10 March 2022Accepted: 11 March 2022A. Taibi, MD, PhDe-mail: abdelkader.taibi@hotmail.FrAnn Surg Oncolhttps://doi.org/10.1245/s10434-022-11657-3FUTUREWhile several IP treatment modalities are currentlyavailable, they still need to provide response to the mainneeds in PM of colorectal origin. Potential treatment set-tings include (1) consolidation of CRS forresectable patients, (2) better response at induction treat-ment for borderline-resectable patients, and (3) improvedquality of life with at least stable disease for unre-sectable patients. Oxaliplatin still seems to be a valuablecytotoxic agent for IP use, potentially improved by asso-ciation with IV 5-FU and repeated administrations. Futureclinical trials should aim to define and test the best treat-ment indications and protocols, and to find solutions toovercome acquired resistance to oxaliplatin. Selection ofpatients for the right IP regimen using chemosensibilityassay of primary cultures or organoid is one of thepromising pathways for the future, but the key for furtherdevelopment remains a round trip from bedside to benchand from bench to bedside.DISCLOSURE O.G.: Gamida. M.H.: ENCARE: consultant fee(institution), Nestlé: research funding, Capnomed: sponsoring ofscientific meetings, MSD, Fresenius: speaker honorary (institution),ERAS society: board member, chair education, ISSPP: board mem-ber, chair, and education. Other authors: None.REFERENCES1. Badrudin D, Sideris L, Leblond FA, Pichette V, Cloutier AS,Drolet P, et al. Rationale for the administration of systemic 5-FUin combination with heated intraperitonal oxaliplatin. Surg Oncol.2018;27(2):275–9.2. Elias D, Lefevre JH, Chevalier J, Brouquet A, Marchal F, ClasseJ-M, et al. Complete cytoreductive surgery plus intraperitonealchemohyperthermia with oxaliplatin for peritoneal carcinomatosisof colorectal origin. J Clin Oncol Off J Am Soc Clin Oncol.2009;27(5):681–5.3. Quénet F, Elias D, Roca L, Goéré D, Ghouti L, Pocard M, et al.Cytoreductive surgery plus hyperthermic intraperitonealchemotherapy versus cytoreductive surgery alone for colorectalperitoneal metastases (PRODIGE 7): a multicentre, randomised,open-label, phase 3 trial. Lancet Oncol. 2021;22(2):256–66.4. Cortés-Guiral D, Hübner M, Alyami M, Bhatt A, Ceelen W,Glehen O, et al. Primary and metastatic peritoneal surfacemalignancies. Nat Rev Dis Primer. 2021;7(1):91.5. Taibi A, Sgarbura O, Hübner M, Bardet MS, Alyami M, Bakrin N,et al. Feasibility and safety of a combination of oxaliplatin-basedpressurized intraperitoneal aerosol chemotherapy with or withoutintraoperative intravenous 5-fluorouracil and leucovorin forpatients with colorectal peritoneal metastases: a multicentrecomparative cohort study. Ann Surg Oncol. 2022. https://doi.org/10.1245/s10434-022-11577-2.Publisher’s Note Springer Nature remains neutral with regard tojurisdictional claims in published maps and institutional affiliations.A. Taibi et al.

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ASO Author Reflections: Is There Still a Role for Intraperitoneal Oxaliplatin for Colorectal Peritoneal Metastases?

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