Phase I and pharmacokinetic study of hepatic arterial infusion with oxaliplatin in combination with folinic acid and 5-fluorouracil in patients with hepatic metastases from colorectal cancer

摘要: Summary Background To determine dose-limiting toxicity (DLT), maximum tolerated dose (MTD), and pharmacokinetics (PK) of oxaliplatin administered as hepatic arterial infusion. Patients methods with isolated metastases from colorectal cancer were treated every three weeks increasing doses (4 hours; starting 25 mg/m2, escalation in steps mg/m2) combination folinic acid (1 hour, 200 5-fluorouracil (2 600 mg/m2). Results Twenty-one patients (median age, 61 years) have been entered all whom are fully evaluable. The DLT has observed at level 6, i.e., 150 mg/m2/cycle consisted leucopenia, obliteration the artery, acute pancreatitis. Overall, mainly nausea/vomlting (16 21 patients), anemia 21), upper abdominal pain (15 sensory neuropathy (10 diarrhea (9 thrombocytopenia 21). mean PK parameters were: terminal half-life ultrafiltrable platin, 17.75 ± 9.29 renal elimination, 48.7% 14.1% applied dose; clearance 135.55 45.32 ml/min. area under plasma-concentration curve (AUC) increased linearly 3.22 0.61 ug h/ml to 18.45 8.90 μg through first five levels (P = 0.0004). Ten eighteen evaluable achieved a complete or partial response (59%). Conclusions recommended for phase II studies is 125 mg/m2 oxaliplatin.