Adjuvant HIPEC to Prevent Colorectal Peritoneal Metastases in High-risk Patients
Condition: Colorectal Neoplasm; Metastasis
MeSH terms: Neoplasm Metastasis; Colorectal Neoplasms
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The prognosis of peritoneal metastases from colorectal cancer has recently improved with
      cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). Although
      outcomes are further improved when early stage peritoneal metastases are treated, adjuvant
      HIPEC has not yet been thoroughly addressed. This prospective pilot study assessed
      feasibility, safety and efficacy of HIPEC performed simultaneously with primary curative
      surgery in colorectal cancer patients with primary tumor-related risk-factors for the
      development of metachronous peritoneal metastases.
    

Detailed description: 
      BACKGROUND Peritoneal surfaces are the second most common site of disease progression for
      colorectal cancer (CRC), following liver metastases. Historically, prognosis of CRC
      peritoneal metastases (PM) was only about 6 months with palliative systemic chemotherapy or
      supportive care. Survival improvements have been reported with cytoreductive surgery and
      hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). However, CRS/HIPEC is more effective
      and safe when early-stage CRC-PM are treated and most patients are not suitable for
      CRS/HIPEC, due to extensive peritoneal and/or systemic disease. Also, in the palliative
      setting, modern systemic therapies appear to be less effective for PM, than non-PM metastatic
      CRC and absence of symptoms and current limitations of imaging hamper early diagnosis and
      treatment of PM. These points would support the use of adjuvant HIPEC to prevent the
      outgrowth of occult peritoneal seeding into macroscopic disease.

      STUDY DESIGN This tudy to assesses feasibility and safety of an integrated approach of
      curative surgery and adjuvant HIPEC performed at the same time as primary surgery in patients
      with primary CRC at high risk for the development of metachronous PM. Patients are
      prospectively selected on the base of preoperative clinical and radiological work-up. At
      surgery, careful exploration of all peritoneal the cavity, and intra-operative pathological
      examination are carried out to confirm clinical-pathological risk-factors for PM development
      Standard adjuvant systemic chemotherapy is intended in the postoperative setting. A matched
      control group will be selected among patients with colorectal cancer undergoing curative
      surgery and standard adjuvant systemic chemotherapy at the same institution and during the
      same period.

      STUDY POPULATION Patients with colorectal cancer undergoing intentionally curative resection
      for primary tumors infiltrating the visceral serosa (T4a) or directly invading adjacent
      organs (T4b), with positive peritoneal washing cytology or resected ovarian or minimal
      peritoneal metastases.

      INTERVENTION Adjuvant HIPEC procedure is performed under general anaesthesia after the
      completion of the surgical procedures. Colon resections for primary tumors are performed
      according to the oncologic principles of adequate lymph-adenectomy.Greater and lesser
      omentectomy and adhesiolysis (if necessary) are performed routinely to ensure optimal
      perfusion during the HIPEC. Tumor deposits on visceral and parietal surfaces are surgically
      removed by formal peritonectomy procedures and/or organ resections, as needed. HIPEC is
      performed with cisplatin (25 mg/m2/l of perfusate) and mitomycin-C (3•3 mg/m2/l of perfusate)
      at 42•5°C for 60 minutes according to the closed-abdomen .technique.

      OUTCOMES Primary end-point is the sensitivity and false positive rate of
      preoperative/intraoperative assessment of primary tumor-related risk-factors for the
      development of peritoneal metastases in patients with colorectal cancer undergoing curative
      surgery..Secondary endpoints are number of participants with adverse events as a measure of
      safety and tolerability, Cumulative incidence of PM, overall and progression-free survival
      are assessed in comparison with matched controls.
    

Intervention name(s): adjuvant HIPEC; surgery
Intervention type(s): Drug; Procedure
Intervention description(s): Closed-abdomen HIPEC with cisplatin (25 mg/m2/l of perfusate) and mitomycin-C (3•3 mg/m2/l of perfusate) at 42•5°C for 60 minutes. Perfusate volume: 4-6 l.; Colon resections for primary tumors were performed according to the oncologic principles of adequate lymph-adenectomy. Complete adhesiolysis, resection of falciform hepatic ligament, greater and lesser omentectomy were performed in all patients to ensure optimal perfusion during the HIPEC. Tumor deposits on visceral and parietal surfaces were surgically removed by formal peritonectomy procedures and/or organ resections, as needed.
Other intervention name(s): Cisplatin, mitomycin-C
Intervention MeSH terms: Cisplatin; Mitomycins; Mitomycin
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: HIPEC; peritoneal lavage