Systemic Chemotherapy With or Without Intraperitoneal Chemohyperthermia in Treating Patients Undergoing Surgery for Peritoneal Carcinomatosis From Colorectal Cancer

OBJECTIVES:

Primary

• Compare overall survival of patients with peritoneal carcinoma of colorectal origin undergoing complete surgical resection and receiving systemic chemotherapy with versus without intraperitoneal chemohyperthermia.

Secondary

• Evaluate recurrence-free survival of these patients.
• Evaluate treatment toxicities.
• Determine morbidity from surgical complications.
• Determine prognostic factors of survival.

OUTLINE: This is a multicenter study. Patients are stratified according to participating center, residual tumor status (R0/R1 vs R2 ≤ 1 mm), prior regimens of systemic chemotherapy (first vs ≥ second), and preoperative systemic chemotherapy for metastatic disease (yes vs no). Patients are randomized to 1 of 2 treatment arms.

All patients undergo maximal surgical resection of the tumor.

• Arm I: Patients receive standard systemic chemotherapy comprising leucovorin calcium IV followed by fluorouracil IV over 30 minutes. Systemic chemotherapy will continue for at least 6 months (before and/or after surgery). Patients must stop systemic chemotherapy at least 1 month before receiving intraperitoneal chemohyperthermia (CHIP). If bevacizumab is given as neoadjuvant therapy, then systemic chemotherapy must be discontinued 6 weeks before beginning CHIP. Patients undergo CHIP comprising oxaliplatin intraperitoneally during surgery and hyperthermia for 30 minutes.
• Arm II: Patients undergo surgery and receive standard systemic chemotherapy comprising leucovorin calcium IV followed by fluorouracil IV over 30 minutes. Systemic chemotherapy will continue for at least 6 months (before and after surgery).

Tumor markers (ACE and CA 19-9) are assessed at baseline, at 1 month after surgery, and then at follow-up visits.

After completion of study therapy, patients are followed at 1 and 3 months, every 3 months for 3 years, and then every 6 months for 2 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed colorectal cancer

• Peritoneal carcinoma extension ≤ 25 (Sugarbaker Index) (determined intraoperatively)

• Planning to receive standard systemic chemotherapy

• Chemotherapy for metastatic cancer should be initiated 3 months after surgery
• No extraperitoneal metastases, including liver and lung metastasis
• No carcinomatosis of other origin besides colorectal, in particular appendical carcinomatosis
• Macroscopically complete resection (R1) or surgical reduction of tumor to a residual thickness ≤ 1 mm (R2) is possible

PATIENT CHARACTERISTICS:

• WHO performance status 0-1
• Life expectancy > 12 weeks
• ANC ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 3 times ULN
• Alkaline phosphatase ≤ 3 times ULN
• Creatinine ≤ 1.25 times ULN
• Eligible for surgery
• No peripheral neuropathy > grade 3
• Not pregnant or nursing
• No other cancer in the past 5 years except basal cell skin cancer or carcinoma in situ of the cervix
• No inability to submit to follow-up medical testing for geographical, social, or psychological reasons
• Affiliated with a social security program
• Not deprived of liberty or under supervision

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior chemohyperthermia
• No concurrent participation in another study of first-line therapy for this cancer