Retrospective comparison between a regular and a split-dose protocol of 5-fluorouracil, cisplatin, and mitoxantrone for the treatment of far advanced hepatocellular carcinoma.

Abstract

BACKGROUND:

In patients with advanced hepatocellular carcinoma (HCC), combination chemotherapy using 5- fluorouracil, cisplatin, and mitoxantrone (FMP) could achieve a response rate > 20%, but the beneficial effect was compromised by formidable adverse events. Chemotherapy given in a split-dose manner was associated with reduced toxicities. In this retrospective study, we compared the efficacies and side effects between a regular and a split-dose FMP protocol approved in our medical center.

METHODS:

From 2005 to 2008, the clinical data of 84 patients with far advanced HCC, who had either main portal vein thrombosis and/or extrahepatic metastasis, were reviewed. Of them, 65 were treated by either regular (n = 27) or split-dose (n = 38) FMP and had completed at least one therapeutic course. The remaining 19 patients were untreated. Clinical parameters, therapeutic responses, survivals and adverse events were compared.

RESULTS:

The median overall survival was 6.0, 5.2, and 1.5 months, respectively, in patients receiving regular FMP, split-dose FMP, and no treatment (regular versus split-dose group, P = 0.447; regular or split-dose versus untreated group; P < 0.0001). Patients receiving split-dose treatment had a significantly lower risk of grade 3/4 neutropenia (51.9 versus 10.5%, P = 0.0005). When the two treated groups were combined, the median overall survival was 10.6 and 3.8 months respectively for patients achieving disease control and progressive disease (P < 0.001). Cox proportion hazard model identified Child-Pugh stage B (hazard ratio [HR], 2.216; P = 0.006), presence of extrahepatic metastasis (HR, 0.574; P = 0.048), and achievement of disease control (HR, 0.228; P < 0.001) as independent factors associated with overall survival. Logistic regression analysis revealed that anti-hepatitis C virus antibody (odds ratio [OR], 9.219; P = 0.002) tumor size (OR, 0.816; P = 0.036), and previous anti-cancer therapy (OR, 0.195; P = 0.017) were significantly associated with successful disease control.

CONCLUSIONS:

Comparable overall survival was observed between patients receiving regular and split-dose FMP therapies. Patients receiving split-dose therapy had a significantly lower risk of grade 3/4 neutropenia. Positive anti-hepatitis C virus antibody, smaller tumor size, and absence of previous anti-cancer therapy were independent predictors for successful disease control.

• Authors: Chau-Ting Yeh, Hui-Chin Chen, Chang-Mu Sung, Cheng-Lung Hsu, Chen-Chun Lin, Kuang-Tse Pan, Jeng-Hwei Tseng, Chien-Fu Hung
• Journal: BMC cancer (BMC Cancer) Vol. 11 Pg. 117 (Mar 31 2011) ISSN: 1471-2407 [Electronic] England
• PMID: 21453495 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Mitoxantrone
• Cisplatin
• Fluorouracil

Topics

• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carcinoma (drug therapy, pathology, physiopathology)
• Cisplatin (administration & dosage, adverse effects)
• Clinical Protocols
• Disease Progression
• Female
• Fluorouracil (administration & dosage, adverse effects)
• Humans
• Liver Neoplasms (drug therapy, mortality, pathology, physiopathology)
• Male
• Middle Aged
• Mitoxantrone (administration & dosage, adverse effects)
• Retrospective Studies
• Survival Analysis