Evaluation, in Humans, of the Correlation Between Hepatotoxicity, Neurotoxicity Induced by Oxaliplatin, and Blood Levels of HMGB1

Evaluation, in Humans, of the Correlation Between Hepatotoxicity, Neurotoxicity Induced by Oxaliplatin, and Blood Levels of HMGB1

Oesogastric and pancreatic adenocarcinomas are poor-prognosis cancers. Incidence of pancreatic cancer drastically increases to such an extent that it will become the second cause of cancer's mortality by 2030. A major challenge is to optimize the therapies for localized setting, when oxaliplatin-based chemotherapy is the standard, before and after surgical excision. Because in 50% of cases oxaliplatin triggers a grade 2-3 sinusoidal obstruction syndrome (SOS) which increases post-operative morbidity, decreases histological response to chemotherapy, increases tumor recurrence, and aggravates the risk of chemotherapy-induced peripheral neuropathy (CIPN).

There is an urgent need to better understand the biological processes involved in SOS, in order to prevent and treat it without stopping or reducing oxaliplatin administration.

The biological link between oxaliplatin and SOS has not been described, but recent murine experiments argue for HMGB1 to be the mediator released after exposure to oxaliplatin and inducing SOS, and thereafter CIPN. To date, no biomarker is established between murine and patient analyses, and the release of HMGB1 after oxaliplatin treatment and its effect on hepatic parenchyma is not described in patients. Investigators hypothesized is that HMGB1 would also been increased in patients after oxaliplatin treatment, and correlated to the development of SOS and CIPN. If confirmed, personalized treatment will be possible to target this pathway.

Therefore, investigators propose to dynamically explore this hypothesis in localized oesogastric and pancreatic cancer patients who will be routinely managed by an initial laparoscopy and post-oxaliplatin surgical excision.

Inclusion Criteria:

• ECOG WHO Performance status = 0 or 1
• Signed and dated informed consent
• Patients with histological diagnosis of oesogastric or pancreatic adenocarcinoma
• Resectable tumors
• Patients able to have a laparoscopy
• In case of absence of peritoneal invasion on the laparoscopy, patient candidate to a chemotherapy schedule by FLOT or FOLFOX in perioperative setting for oesogastric adenocarcinoma, or FOLFIRINOX in perioperative setting for pancreatic adenocarcinoma
• Registration in a national health care system (CMU included)
• Patient speak and understand the french

Exclusion Criteria:

• Histology other than adenocarcinoma
• Metastatic disease
• History of previous treatment with oxaliplatine
• History of systemic chemotherapy administration within 5 years prior to inclusion,
• Patient with an non balanced progressive condition/disease (liver failure, renal failure (creatinine clearance <30mL/min), respiratory failure, congestive heart failure, myocardial infarction in the last 6 months, etc.),
• Patient on curative dose anticoagulant,
• Patient with complete dihydropyrimidine dehydrogenase deficiency (Uracilemia ≥ 150 ng/ml),
• Patient not operable for the pathology concerned,
• Pregnant or breastfeeding woman, woman of childbearing age who has not performed a pregnancy test before the procedure,
• Patient with legal incapacity (person deprived of liberty or under curatorship, stutorship, safeguard of justice),
• Patient who, for psychiatric, social, family or geographical reasons, cannot be followed and/or comply with the requirements of the study,,
• Discovery of peritoneal invasion during the peritoneal exploratory of the laparoscopy