A phase II trial of continuous-infusion 5-fluorouracil, mitoxantone and cisplatin for metastatic hepatocellular carcinoma

Abstract

4081 Backgrounds: Chemotherapy for hepatocellular carcinoma (HCC) has only limited value in clinical practice, because no chemotherapy regimen has been shown to have predictable activity against this cancer. The aim of this study was to evaluate the anti-tumor activity and toxicity of continuous-infusion 5-fluorouracil, mitoxantone and cisplatin (FMP therapy) in chemo-naïve patients with metastatic HCC. Methods: Fifty-one patients with metastatic HCC who had no prior systemic chemotherapy with measurable extrahepatic metastasis, adequate liver and renal function, and adequate bone marrow reserve were enrolled in this study. The therapy consisted of cisplatin 80 mg/m2 and mitoxantrone 6 mg/m2 intravenously on day 1, and continuous intravenous infusion 5-FU 450 mg/m2/day on days 1 through 5. Treatment was repeated every 4 weeks to a maximum of 6 courses with dose adjustments based on the toxic effects observed, if there was no evidence of tumor progression or unacceptable toxicity. Results: Of all 51 enrolled patients, 14 patients achieved a partial response (27%; 95% confidence interval, 17% to 54%) with a median duration of 7.6 months (range, 2.3 to 18.4). Twenty-seven patients (53%) showed no change and nine (18%) showed progressive disease. Serum AFP level was reduced more than 50% in only 21% of the patients who had shown a pretreatment level of 100 U/ml or greater, but serum PIVKA II level was reduced more than 50% in 58% of the patients who had a pretreatment level of 100 mAU/ml or greater. The median survival time, 1-year survival and median time to progression for all patients were 11.6 months, 44.5%, and 4.0 months respectively. The main grade 3 and 4 toxicities suffered by patients were leukocytopenia (67%), neutropenia (71%), thrombocytopenia (27%), glutamic oxaloacetic transaminase (37%), and glutamic pyruvic transaminase (41%). These toxicities were generally brief and reversible with the exception of one treatment-related death of acute hepatic failure due to neutropenic sepsis. Conclusion: FMP therapy has significant anti-tumor activity with tolerable toxicity in patients with metastatic HCC. No significant financial relationships to disclose.