Irinotecan hepatic arterial infusion chemotherapy for hepatic metastases from colorectal cancer: results of a phase I clinical study.

BACKGROUND: Hepatic arterial infusion chemotherapy is a promising approach in liver metastases from colorectal cancer, but chemical hepatitis, biliary sclerosis, arterial thrombosis and right upper quadrant pain are limiting factors. Irinotecan (CPT-11) is an active drug in colorectal cancer. We planned a short hepatic arterial infusion of CPT-11 to describe the toxicity, to determine the dose-limiting toxicity, and to define the doses of CPT-11 to be recommended for phase II studies. PATIENTS AND METHODS: Fourteen patients with a median liver substitution of 30% (10-60%) were enrolled. All patients received hepatic arterial infusion chemotherapy with CPT-11 on an outpatient basis every 3 weeks as a short, 30-min infusion. RESULTS: At 240 mg/m2, 2 of 4 patients experienced grade 4 diarrhea and neutropenia, and 3 of them also reported grade 4 abdominal pain of the right upper quadrant. The maximum tolerated dose was reached at 240 mg/m2. The recommended doses of CPT-11 for phase II studies is 200 mg/m2, given every 3 weeks. CONCLUSIONS: CPT-11 presents a low hepatic toxic profile and could be considered a new active drug, suitable for hepatic arterial infusion in liver metastases from colorectal cancer.

Treatment of unresectable malignant abdominal, pelvic and thoracic tumors using abdominal pelvic and thoracic stop-flow chemotherapy.

BACKGROUND: Stop-flow perfusion (SFP) has been recently used to enhance the effects of chemotherapy in patients with locally advanced tumors. PATIENTS AND METHODS: Over a 2-year period we performed abdominal, pelvic and thoracic SFP in 12 patients with unresectable or metastatic tumors, using balloon catheters inserted into the abdominal aorta and inferior vena cava. Blood flow was occluded and hypoxic extracorporeal perfusion or SFP was performed for advanced diseases. The chemotherapeutic agents were directly administered into the aorta and/or inferior vena cava for thoracic SFP. The procedure was repeated in each patient, with one-month interval between sessions. Haemofiltration was also applied in two patients with generalized abdominal disease in order to reduce systemic toxicity. RESULTS: At post-operative CT or MRI follow-up, tumor shrinkage of more than 50% was observed in six patients, while post-SFP chemotherapy surgical resection of the tumors became feasible in four cases. The relief of pain, wherever present, was dramatic in the immediate post-operative period. Overall clinical improvement was achieved in all 12 patients. Post-operative recovery was uneventful in all but two patients, who developed minor systemic toxicity. CONCLUSION: SFP appears to be a safe technique with low morbidity which improves the quality of life of cancer patients and allows satisfactory control of locally advanced tumors and metastatic carcinomatosis.