Background No effective systemic therapy exists for patients with advanced hepatocellular carcinoma. A preliminary study suggested that sorafenib, an oral multikinase inhibitor of the vascular endothelial growth factor receptor, the platelet-derived growth factor receptor, and Raf may be effective in hepatocellular carcinoma. Methods In this multicenter, phase 3, double-blind, placebo-controlled trial, we randomly assigned 602 patients with advanced hepatocellular carcinoma who had not received previous systemic treatment to receive either sorafenib (at a dose of 400 mg twice daily) or placebo. Primary outcomes were overall survival and the time to symptomatic progression. Secondary outcomes included the time to radiologic progression and safety. Results At the second planned interim analysis, 321 deaths had occurred, and the study was stopped. Median overall survival was 10.7 months in the sorafenib group and 7.9 months in the placebo group (hazard ratio in the sorafenib group, 0.69; 95% confidence interval, 0.55 to 0.87; P<0.001). There was no significant difference between the two groups in the median time to symptomatic progression (4.1 months vs. 4.9 months, respectively, P=0.77). The median time to radiologic progression was 5.5 months in the sorafenib group and 2.8 months in the placebo group (P<0.001). Seven patients in the sorafenib group (2%) and two patients in the placebo group (1%) had a partial response; no patients had a complete response. Diarrhea, weight loss, hand-foot skin reaction, and hypophosphatemia were more frequent in the sorafenib group. Conclusions In patients with advanced hepatocellular carcinoma, median survival and the time to radiologic progression were nearly 3 months longer for patients treated with sorafenib than for those given placebo.

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Sorafenib in Advanced Hepatocellular Carcinoma

EASL-EORTC clinical practice guidelines : management of hepatocellular carcinoma

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.24199

Management of hepatocellular carcinoma: An update

Since the publication of the American Association for the Study of Liver Diseases (AASLD) practice guidelines on the management of hepatocellular carcinoma (HCC) in 2005, new information has emerged that requires that the guidelines be updated. The full version of the new guidelines is available on the AASLD Web site at http://www.aasld.org/practiceguidelines/ Documents/Bookmarked%20Practice%20Guidelines/ HCCUpdate2010.pdf. Here, we briefly describe only new or changed recommendations.

/pdf/aasld-practice-guideline-management-of-hepatocellular-51bocalv0r.pdf

AASLD PRACTICE GUIDELINE Management of Hepatocellular Carcinoma: An Update

Summary Background Most cases of hepatocellular carcinoma occur in the Asia-Pacific region, where chronic hepatitis B infection is an important aetiological factor. Assessing the efficacy and safety of new therapeutic options in an Asia-Pacific population is thus important. We did a multinational phase III, randomised, double-blind, placebo-controlled trial to assess the efficacy and safety of sorafenib in patients from the Asia-Pacific region with advanced (unresectable or metastatic) hepatocellular carcinoma. Methods Between Sept 20, 2005, and Jan 31, 2007, patients with hepatocellular carcinoma who had not received previous systemic therapy and had Child-Pugh liver function class A, were randomly assigned to receive either oral sorafenib (400 mg) or placebo twice daily in 6-week cycles, with efficacy measured at the end of each 6-week period. Eligible patients were stratified by the presence or absence of macroscopic vascular invasion or extrahepatic spread (or both), Eastern Cooperative Oncology Group performance status, and geographical region. Randomisation was done centrally and in a 2:1 ratio by means of an interactive voice-response system. There was no predefined primary endpoint; overall survival, time to progression (TTP), time to symptomatic progression (TTSP), disease control rate (DCR), and safety were assessed. Efficacy analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00492752. Findings 271 patients from 23 centres in China, South Korea, and Taiwan were enrolled in the study. Of these, 226 patients were randomly assigned to the experimental group (n=150) or to the placebo group (n=76). Median overall survival was 6·5 months (95% CI 5·56–7·56) in patients treated with sorafenib, compared with 4·2 months (3·75–5·46) in those who received placebo (hazard ratio [HR] 0·68 [95% CI 0·50–0·93]; p=0·014). Median TTP was 2·8 months (2·63–3·58) in the sorafenib group compared with 1·4 months (1·35–1·55) in the placebo group (HR 0·57 [0·42–0·79]; p=0·0005). The most frequently reported grade 3/4 drug-related adverse events in the 149 assessable patients treated with sorafenib were hand-foot skin reaction (HFSR; 16 patients [10·7%]), diarrhoea (nine patients [6·0%]), and fatigue (five patients [3·4%]). The most common adverse events resulting in dose reductions were HFSR (17 patients [11·4%]) and diarrhoea (11 patients [7·4%]); these adverse events rarely led to discontinuation. Interpretation Sorafenib is effective for the treatment of advanced hepatocellular carcinoma in patients from the Asia-Pacific region, and is well tolerated. Taken together with data from the Sorafenib Hepatocellular Carcinoma Assessment Randomised Protocol (SHARP) trial, sorafenib seems to be an appropriate option for the treatment of advanced hepatocellular carcinoma. Funding Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals, Inc.

https://www.thelancet.com/pdfs/journals/lanonc/PIIS1470-2045(08)70285-7.pdf

Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial.

IntroductionSomatostatin analogs are currently indicated for therelief of symptoms associated with hypersecretion syn -dromes in patients with gastroenteropancreatic neu -roendocrine tumors (NETs) . However, antiproliferativeefficacy of somatostatin analogs is still debated .In patients with metastatic well-differentiated neu -roendocrine tumors (NETs), antiproliferative treatmentis intended to reduce tumor burden, delay tumor pro -gression and prolong survival. Available antiprolifera -tive treatment options include surgical, ablative, radio -therapeutic , and pharmacological strategies, most ofwhichareassociatedwithadverseeffectsthatcancom -promisequalityoflife.Somatostatinanalogsareassoci -ated with minimal adverse effects. For this reason, theyhave been offered to patients with metastatic diseasenot amenable to surgery. However, the ability of so -matostatin analogs to control tumor growth remainscontroversial. Antiproliferativeeffectshavebeenreport -edinuncontrolled

Evolving perspectives on antiproliferative effects of octreotide treatment: the PROMID data

II caso clinico in discussione si riferisce ad un paziente anziano di sesso maschile, delleta di 78 anni, giunto all'osservazione dell'Unita di Oncologia Medica dell'Universita di Pisa con sintomatologia suggestiva di tumore neuroendocrino, caratterizzata da diarrea e calo ponderale insorti da circa 5 mesi. Dopo aver documentato mediante clisma del colon a doppio contrasto una massa a livello del ceco e la presenza di lesioni ripetitive multiple a livello epatico mediante ecografia, il paziente estato sottoposto ad intervento chirurgico di emicolectomia destra e biopsia epatica. L'esame istologico ha permesso di formulare una diagnosi di tumore carcinoide e la successiva esecuzione di una scintigrafia con octreotide (octreoscan) e risuItata positiva a livello delle lesioni epatiche. E stato quindi eseguito un profilo completo dei marcatori tumorali che ha documentato l'aumento significativo dei livelli di acido 5-idrossindolacetico urinario (u-5-IHAA), della cromogranina A (p-CgA) e della 5idrossitriptamina (5-HT), con valori nei limiti della norma per quanta riguardava gli altri marker tumorali (Tabella 1). Seguendo l'iter diagnostico ritenuto attualmente pili corretto, e stata effettuata la caratterizzazione istologica e immunoistochimica, valutando oltre al grado di differenziazione della neoplasia, parametro oggi ritenuto rilevante dal punto di vista prognostico e terapeutico, i parametri seguenti (Tabella 2):

Sergio Ricci

Papers

Evolving perspectives on antiproliferative effects of octreotide treatment: the PROMID data

Efficacia Di Un Trattamento Con Octreotide Lar in Un Paziente Anziano Affetto Da Carcinoide Cecale