Treatment of Primary Peritoneal Carcinosis of Digestive Origin Using Cytoreductive Surgery and Hyperthermic Intraoperative Peritoneal Chemotherapy With Mitomycin C and Irinotecan

Treatment of Primary Peritoneal Carcinosis of Digestive Origin Using Cytoreductive Surgery and Hyperthermic Intraoperative Peritoneal Chemotherapy With Mitomycin C and Irinotecan

This is an open, non-randomized, phase I-II, pilot study, which evaluates the combination of optimum cytoreductive surgery and hyperthermic intraoperative peritoneal chemotherapy (HIPEC) with mitomycin C (MMC) and irinotecan. The latter drug will be administered in escalating doses to patients with gastric, colorectal, appendicular, or primary peritoneal carcinosis (PC).

Inclusion Criteria:

• Patients with a peritoneal carcinosis (PC) either of digestive origin or primary: a colorectal or gastric carcinosis, a peritoneal pseudomyxoma or mesothelioma, or a primary carcinosis of the peritoneum regardless the number of prior treatment lines.
• A PC and primary tumor considered to be resectable according to preoperative clinical and paraclinical data: absence of mesenteric retraction and absence of bladder invasion.
• Patients in good general health (ASA ≤ 2).
• Absence of cardiorespiratory failure (PaO2 > 60 mmHg in a stable condition, dyspnea ≤ NYHA stage 1, left ventricular ejection fraction > 60%.).
• Prothrombin level >70 %, total bilirubin < 2 x the normal level, ASAT and ALAT < 2.5 x normal levels, and alkaline phosphatases < 5 x normal levels.
• Creatinine clearance > 60 ml/min, polynuclear neutrophils > 1500/mm3, and a white blood cell count > 4000 /mm3.
• Patients who give written, informed consent.
• Patients affiliated with the French universal healthcare system.

Exclusion Criteria:

• Patients with a PC with ovarian, mammary, biliary, pancreatic, or bronchial origin.
• Evolutive patients after systemic chemotherapy.
• Patients with a PC considered to be irresectable according to preoperative clinical and paraclinical data: mesenteric retraction or bladder invasion.
• Patients in poor general health (ASA > 2).
• Cardiorespiratory failure (dyspnea > NYHA stage 1, PaO2 < 60 mmHg in a stable condition)
• Prothrombin level < 70 %.
• Any brain abnormality showing on the head scan.
• Signs of heart failure and especially left ventricular ejection fraction < 60% on the cardiac ultrasound.
• Thrombocytopenia < 100 000 / mm3
• Visceral metastases other than a single resectable liver metastasis.
• Pregnancy or breast feeding.
• Chronic inflammatory intestinal disease and/or an intestinal obstruction.
• History of severe hypersensitivity to irinotecan hydrochloride trihydrate or one of the excipients of Campto.
• Bilirubinemia > 3 times the normal upper limit
• Yellow fever vaccine.
• Prophylactic treatment with phenytoin.
• Severe medullary insufficiency.