RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing
so they stop growing or die. Combining more than one chemotherapy drug and giving them in
different ways may kill more tumor cells. It is not yet known whether surgery followed by
chemotherapy is more effective with or without continuous hyperthermic peritoneal perfusion
in treating peritoneal carcinomatosis.
PURPOSE: This randomized phase III trial is studying chemotherapy and continuous
hyperthermic peritoneal perfusion after surgery to see how well they work compared to
chemotherapy alone after surgery in treating patients with peritoneal carcinomatosis from
- Compare time to intraperitoneal tumor progression after laparotomy and tumor debulking
with vs without continuous hyperthermic peritoneal perfusion in patients with
peritoneal carcinomatosis from low-grade gastrointestinal adenocarcinoma.
- Compare the progression-free and overall survival of patients treated with these
- Compare the quality of life of patients treated with these regimens.
- Compare the patterns of failure in patients treated with these regimens.
OUTLINE: This is a randomized study. Patients are stratified according to prior systemic
chemotherapy (yes vs no), prior debulking surgery (yes vs no), and ability to debulk tumor
(optimal vs sub-optimal debulking).
Patients undergo cytoreductive surgery and at the end of the debulking procedure are
randomized to 1 of 2 treatment arms.
- Arm I: Patients receive continuous hyperthermic peritoneal perfusion (CHPP) with
cisplatin over 90 minutes. Patients have a peritoneal dialysis catheter inserted at the
end of the procedure in order to receive paclitaxel and fluorouracil postoperatively
(once between days 7 and 12).
- Arm II: Patients receive no CHPP or postoperative intraperitoneal chemotherapy.
Approximately 4-6 weeks after surgery, all patients receive systemic chemotherapy with
oxaliplatin IV over 2 hours on day 1 and leucovorin calcium IV over 2 hours on days 1,
2, 15, and 16. Patients also receive fluorouracil IV over 15-30 minutes followed by
fluorouracil IV continuously over 22 hours beginning on days 1, 2, 15, and 16.
Treatment repeats every 4 weeks for up to 4 courses in the absence of disease
progression or unacceptable toxicity.
Quality of life is assessed at baseline; 6 weeks postoperatively; after every other course
of systemic chemotherapy; and then every 3 months for 2 years, every 4 months for 2 years,
and then every 6 months thereafter.
Patients are followed every 3 months for 1 year, every 4 months for 2 years, and then every
6 months until 5 years from treatment date (surgery) or evidence of intraperitoneal tumor
PROJECTED ACCRUAL: A total of 82 patients (41 per treatment arm) will be accrued for this
study within 48 months.
- Histologically or cytologically confirmed peritoneal carcinomatosis from low-grade
mucinous adenocarcinoma of the gastrointestinal tract
- No imageable disease outside of the peritoneal cavity by radiological workup
- Presence of abnormalities consistent with disease that can be debulked to a residual
size of less than 1 cm in diameter per tumor deposit, as shown on radiologic workup
or prior abdominal exploration
- 18 and over
- ECOG 0-2
- More than 16 weeks
- Absolute neutrophil count > 1,500/mm^3
- Platelet count ≥ 75,000/mm^3
- Bilirubin < 3 times upper limit of normal (ULN)
- AST and ALT ≤ 5 times ULN
- Creatinine ≤ 1.5 mg/dL OR
- Creatinine clearance > 60 mL/min
- No significant irreversible ischemia on a stress thallium study* OR
- Ejection fraction ≥ 40%* NOTE: *Only for patients at increased risk for coronary
artery disease or cardiac dysfunction
- FEV_1 ≥ 1.2 liters* OR
- Maximum voluntary ventilation ≥ 50% of expected* NOTE: *Only for patients with
shortness of breath with minimal exertion or for those who are at increased risk for
- Not pregnant or nursing
- Fertile patients must use effective contraception
- Weight ≥ 66 pounds (30 kg)
- No other concurrent medical problems that would place patient at an unacceptable risk
for a major surgical procedure
- No grade 3 or greater neurological toxicity
PRIOR CONCURRENT THERAPY:
- At least 30 days since prior immunotherapy and recovered
- At least 30 days since prior chemotherapy and recovered
- No prior intraperitoneal chemotherapy failure
- No more than 1 prior systemic chemotherapy regimen
- Not specified
- At least 30 days since prior radiotherapy and recovered
- See Disease Characteristics
- No more than 1 prior operative procedure to debulk disease
- No prior continuous hyperthermic peritoneal perfusion