Systemic therapy for advanced hepatocellular carcinoma: a review

Nowak, Anna K.; Chow, Pierce K. H.; Findlay, Michael

doi:10.1016/j.ejca.2004.02.027

Cited by 162 publications

(91 citation statements)

References 130 publications

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“…14,15 In 2 recent, large, randomized controlled trials, it was demonstrated that the multikinase inhibitor sorafenib significantly prolonged survival in patients with advanced HCC, even when the primary lesion was accompanied by extrahepatic metastases; now, sorafenib is widely regarded as the standard treatment for such patients. 16,17 However, the clinical course for patients with extrahepatic metastasis has not yet been fully elucidated, and the prognostic factors remain unclear.…”

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confidence: 99%

Hepatocellular carcinoma with extrahepatic metastasis

Uchino

Tateishi

Shiina

et al. 2011

Cancer

383

322

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BACKGROUND: Despite significant advances in the treatment of intrahepatic lesions, the prognosis for patients with hepatocellular carcinoma (HCC) who have extrahepatic metastasis remains poor. The objective of this study was to further elucidate the clinical course and prognostic determinants of patients with this disease. METHODS: In total, 342 patients who had HCC with extrahepatic metastasis were enrolled. The metastases were diagnosed at initial presentation with HCC in 28 patients and during follow-up in the remaining patients. The authors analyzed clinical features, prognoses, and treatments and established a scoring system to predict prognosis using a split-sample method with a testing set and a training set. RESULTS: The most frequent site of extrahepatic metastasis was the lung followed by lymph nodes, bone, and adrenal glands. These metastases were related directly to death in only 23 patients (7.6%). The median survival after diagnosis of extrahepatic metastasis was 8.1 months (range, 0.03-108.7 months). In univariate analysis of the training set (n ¼ 171), performance status, Child-Pugh classification, the number and size of intrahepatic lesions, macroscopic vascular invasion, symptomatic extrahepatic metastases, a-fetoprotein levels, and complete responses to treatment were associated significantly with prognosis. On the basis of multivariate analysis, a scoring system was developed to predict prognosis that assessed uncontrollable intrahepatic lesions, extent of vascular invasion, and performance status. This scoring system was validated in the testing set (n ¼ 171) and produced a concordance index of 0.73. CONCLUSIONS: The controllability of intrahepatic lesions and performance status were identified as important prognostic factors in patients with advanced HCC who had extrahepatic metastasis. Cancer 2011;117:4475-

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confidence: 99%

Hepatocellular carcinoma with extrahepatic metastasis

Uchino

Tateishi

Shiina

et al. 2011

Cancer

383

322

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“…3,4 Long-term results similar to those for surgery have been reported with nonsurgical local abla-tive therapies such as percutaneous ethanol injection, 5 radiofrequency ablation, 6 and transarterial chemoembolization. 7 In addition, numerous cytotoxic agents have been investigated in trials comprising patients with HCC, 8 and tumor response rates with systemically administered cytotoxic drugs are generally low, although they may be slightly higher when drugs are administered regionally, with or without embolization. 9 Any benefit from cytotoxic therapy must be weighed against the associated toxicity.…”

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confidence: 99%

Use of tamoxifen in advanced‐stage hepatocellular carcinoma

Nowak

Stockler

Chow

et al. 2005

Cancer

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BACKGROUNDHepatocellular carcinoma (HCC) is the third most common cause of cancer mortality worldwide. Survival is poor for patients with advanced‐stage HCC, and small trials of tamoxifen for patients with this disease have shown conflicting results. The authors conducted a systematic review of randomized clinical trials to compare the effect of a tamoxifen‐containing arm with a nontamoxifen‐containing arm in advanced HCC.METHODSEligible trials were identified from the Cochrane Hepato‐Biliary Group register and other databases. Studies were selected for inclusion and their methodologic quality assessed by three independent reviewers. Hazard ratios (HR) were derived for overall survival where possible. Metaanalysis was performed using a fixed‐effect model.RESULTSThe authors identified 10 randomized trials with a total of 1709 patients. Use of tamoxifen had no effect on median survival (HR, 1.05; 95% confidence interval, 0.94–1.16; P = 0.4) or tumor response rate. The findings were stable in sensitivity analyses and were not affected by publication bias or inclusion of low‐quality studies or studies reported in abstract form only. Few adverse events or withdrawals were noted.CONCLUSIONSThere was no support for the therapeutic use of tamoxifen in advanced HCC, nor for its use as a control arm in future clinical trials. Cancer 2005. © 2005 American Cancer Society.

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“…Systemic chemotherapy and immunotherapy (IFN-a) have only marginal activity and are poorly tolerated in cirrhotic patients (Llovet et al, 2000;Nowak et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…The role of trans-arterial chemo-embolisation in the management of advanced HCC remains questionable, although there are some studies reporting survival benefit (Llovet et al, 2002;Lo et al, 2002;Groupe d'Etude et de Traitement du Carcinome Hepatocellulaire, 2004). Chemotherapeutic options have also been reported as disappointing and hazardous in the management of HCC due to the impaired hepatic function and the relative chemoresistance (Nowak et al, 2004). Owing to its anti-angiogenic and presumably antiproliferative properties, interferon-a has been used to treat advanced HCC but failed to be efficient in improving survival (Llovet et al, 2000).…”

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Efficacy of the combination of long-acting release octreotide and tamoxifen in patients with advanced hepatocellular carcinoma: a randomised multicentre phase III study

Verset

Verslype²,

Reynaert

et al. 2007

Br J Cancer

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To assess the efficacy of the combination of long-acting release (LAR) octreotide and tamoxifen (TMX) for the treatment of advanced hepatocellular carcinoma (HCC). A total of 109 patients with advanced HCC were randomised to receive octreotide LAR combined with TMX (n ¼ 56) (experimental treatment group) or TMX alone (n ¼ 53; control group). The clinical, biological and tumoural parameters were recorded every 3 months until death. Primary end point was patient survival; secondary end points were the impact of therapy on tumour response, quality of life and variceal bleeding episodes. Univariate and multivariate analyses were performed for assessment of specific prognostic factors. The median survival was 3 months (95% CI 1.4 -4.6) for the experimental treatment group and 6 months (CI 95% 2 -10) for the control group (P ¼ 0.609). There was no difference in terms of a-foetoprotein (a-FP) decrease, tumour regression, improvement of quality of life and prevention of variceal bleeding between the two groups. Variables associated with a better survival in the multivariate analysis were: presence of cirrhosis, a-FP level o400 ng ml À1 and Okuda stage I. The combination of octreotide LAR and TMX does not influence survival, tumour progression or quality of life in patients with advanced HCC.

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Systemic therapy for advanced hepatocellular carcinoma: a review

Cited by 162 publications

References 130 publications

Hepatocellular carcinoma with extrahepatic metastasis

Hepatocellular carcinoma with extrahepatic metastasis

Use of tamoxifen in advanced‐stage hepatocellular carcinoma

Efficacy of the combination of long-acting release octreotide and tamoxifen in patients with advanced hepatocellular carcinoma: a randomised multicentre phase III study

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