Intraperitoneal Hyperthermic Perfusion With Oxaliplatin in Treating Patients With Stage IV Peritoneal Cancer Due to Appendix Cancer or Colorectal Cancer

OBJECTIVES:

• Determine the toxicity of intraperitoneal hyperthermic chemoperfusion with oxaliplatin in patients with stage IV peritoneal surface malignancies from primary colorectal or appendiceal cancer.
• Determine the pharmacokinetics of this drug in perfusate, normal peritoneum, and peritoneal surface tumors in these patients.
• Evaluate the expression of proteins involved in the apoptotic and stress-inducible heat shock protein pathways (e.g., Fas, TRAIL, DISC components [FADD, TRADD, FLIP, and caspase 8], mitochondrial proteins [Bax, Bak, Bcl-2, Bcl-X_L], and heat shock proteins [HSPs 27, 40, 70 and 90]) before and after drug therapy.

OUTLINE: This is a nonrandomized, open-label, dose-escalation study.

Patients undergo gross tumor resection on day 1. After tumor debulking, patients receive oxaliplatin over 2 hours by intraperitoneal hyperthermic chemotherapy (IPHC).

Cohorts of 3-6 patients in each stratum receive escalating doses of oxaliplatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.

Patients undergo blood and tissue sampling before and after IPHC for pharmacokinetic studies and for evaluation of proteins involved in apoptosis and heat-shock-mediated cell death (e.g., Fas, TRAIL, FADD, TRADD, FLIP, caspase 8, Bax, Bak, Bcl-X, and heat shock proteins 27, 40, 70, and 90).

After completion of study treatment, patients are followed periodically for at least 1 year.

PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed colorectal or appendiceal cancer

• Stage IV disease
• Peritoneal surface dissemination of disease (peritoneal carcinomatosis)
• Measurable disease according to RECIST criteria
• No active CNS metastases

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Creatinine ≤ 1.5 mg/dL OR creatinine clearance > 60 mL/min
• Bilirubin ≤ 1.5 mg/dL
• Alkaline phosphatase ≤ 3 times upper limit of normal (ULN)
• AST and ALT ≤ 3 times ULN
• No active infection or fever ≥ 101.3°F within the past 3 days
• No other malignancy within the past 5 years except curatively treated basal cell skin cancer, cervical intra-epithelial neoplasia, or localized prostate cancer with a current prostate-specific antigen of < 1.0 mg/dL on 2 successive evaluations, ≥ 3 months apart, with the last evaluation within the past 4 weeks
• No peripheral neuropathy ≥ grade 2
• No other medical condition, mental illness, or substance abuse that, in the opinion of the principal investigator, would preclude study compliance
• No known hypersensitivity to any component of oxaliplatin
• No known HIV positivity
• No hepatitis B or C positivity (active, previously treated, or both)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients and their partners must use effective contraception during and for 90 days after completion of study treatment

PRIOR CONCURRENT THERAPY:

• Recovered from prior surgery, radiotherapy, and other anticancer therapies
• More than 30 days since prior and no other concurrent investigational therapy
• No prior radiotherapy to > 25% of bone marrow
• No prior allogeneic stem cell transplantation
• No concurrent antiretroviral therapy