title: Prospective randomized trial evaluating mandatory second look surgery with HIPEC and CRS vs. standard of care in patients at high risk of developing colorectal peritoneal metastases.
abstract: BACKGROUND
  The standard of care for colorectal peritoneal carcinomatosis is evolving from chemotherapy to cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with disease limited to the peritoneum. Peritoneal carcinomatosis from colorectal cancer treated with chemotherapy alone results in median survival of 5 to 13 months, whereas CRS with HIPEC for early peritoneal carcinomatosis from colorectal cancer resulted in median survival of 48-63 months and 5 year survival of 51%.Completeness of cytoreduction and limited disease are associated with longer survival, yet early peritoneal carcinomatosis is undetectable by conventional imaging. Exploratory laparotomy can successfully identify early disease, but this approach can only be justified in patients with high risk of peritoneal carcinomatosis. Historical data indicates that patients presenting with synchronous peritoneal carcinomatosis, ovarian metastases, perforated primary tumor, and emergency presentation with bleeding or obstructing lesions are at high risk of peritoneal carcinomatosis. Approximately 55% of these patient populations will develop peritoneal carcinomatosis. We hypothesize that performing a mandatory second look laparotomy with CRS and HIPEC for patients who are at high risk for developing peritoneal carcinomatosis from colorectal cancer will lead to improved survival as compared to patients who receive standard of care with routine surveillance.
  
  
  METHODS
  This study is a prospective randomized trial designed to answer the question whether mandatory second look surgery with CRS and HIPEC will prolong overall survival compared to the standard of care in patients who are at high risk for developing peritoneal carcinomatosis from colorectal cancer (CRC). Patients with CRC at high risk for developing peritoneal carcinomatosis who underwent curative surgery and subsequently received standard of care adjuvant chemotherapy will be evaluated. The patients who remain without evidence of disease by imaging, physical examination, and tumor markers for 12 months after the primary operation will be randomized to mandatory second look surgery or standard-of-care surveillance. At laparotomy, CRS and HIPEC will be performed with intraperitoneal oxaliplatin with concurrent systemic 5-fluorouracil and leucovorin. Up to 100 patients will be enrolled to allow for 35 evaluable patients in each arm; accrual is expected to last 5 years.
  
  
  BACKGROUND
  ClinicalTrials.gov ID: NCT01095523.
authors.affiliation: Surgery Branch, CCR, NCI, Bethesda, MD 20892-120, USA.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Ripley
authors.forename: Jeremy L
authors.initials: JL
authors.lastname: Davis
authors.forename: Clinton D
authors.initials: CD
authors.lastname: Kemp
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Toomey
authors.forename: Itzhak
authors.initials: I
authors.lastname: Avital
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D010478:Chemotherapy, Cancer, Regional Perfusion; D015179:Colorectal Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D018572:Disease-Free Survival; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D006979:Hyperthermia, Induced / Q000009:adverse effects; D007813:Laparotomy / Q000009:adverse effects; D002955:Leucovorin / Q000008:administration & dosage; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010534:Peritoneal Neoplasms / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D018401:Sample Size; D024162:Second-Look Surgery / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D002955:Leucovorin; D005472:Fluorouracil