Phase I study of hepatic arterial infusion of oxaliplatin in advanced hepatocellular cancer: a brown university oncology group study.

PURPOSE

We performed a phase I study to evaluate the feasibility and determine the maximally tolerated dose of hepatic arterial infusion (HAI) of oxaliplatin in advanced hepatocellular carcinoma (HCC).

PATIENTS AND METHODS

Patients with unresectable or recurrent HCC received HAI-oxaliplatin over 2 hours at dose escalation levels of 90, 110, 130, and 150 mg/m given every 3 weeks. The therapy was continued until disease progression or excessive toxicity not amenable to appropriate modifications. Restaging was performed after every 2 cycles.

RESULTS

A total of 23 patients were enrolled, with 17 patients evaluable for toxicity assessment. The median age was 63 years (range: 47-84 years), with 22 men and 1 woman. Stage distribution was as follows: stage II, 3 patients; stage III, 12 patients; and stage IV, 8 patients. A total of 53 cycles (range: 1-3) of HAI-oxaliplatin were delivered. The conventional grade 3/4 hematologic and gastrointestinal toxicities were infrequent. Among 17 evaluable patients receiving >2 cycles, 3 patients had partial responses and 8 had stable disease. A greater than 50% reduction in alphafetoprotein was seen in the 3 patients with partial responses and 3 patients with stable disease.

CONCLUSIONS

HAI-oxaliplatin is a feasible, well tolerated, and demonstrated activity in this advanced HCC cohort. HAI-oxaliplatin 150 mg/m every 3 weeks was determined as the dose for further evaluation in phase II trials.