Child-Pugh Status Research Articles

Sorafenib for Egyptian patients with advanced hepatocellular carcinoma; single center experience

BackgroundAccording to the results of a number of phase 3 randomized studies, sorafenib is the only approved systemic therapy for advanced HCC; however the issue of high economic cost remains challenging; thus we have conducted this retrospective analysis of our HCC patients treated with sorafenib. MethodsHCC patients treated at Ain Shams University Hospitals, in the period between 2010 and 2012 were reviewed. Eligible patients were those who had received sorafenib for advanced HCC not eligible for or progressed after surgery or locoregional therapy. We investigated the impact of baseline clinicopathological factors (age, gender, child status, performance score, BCLC tumor stage, cause of chronic liver disease, median baseline alpha fetoprotein level and previous treatment received for HCC) on overall survival (OS) in an adjusted Cox regression model. Results41 patients were included in the analysis fulfilling the inclusion criteria. At a median follow up period of 13months, the median PFS for the whole group was 4months; the median OS for the whole group is 6.25months. Multivariate analysis identified three baseline characteristics that were prognostic indicators for overall survival: ECOG performance status (median OS for ECOG 1=7.01months and for ECOG 2=3.03months), Child–Pugh status (median OS for child A=12.04months and for child B=5.23months), and median baseline levels of alpha-fetoprotein. ConclusionsIn limited resource countries like Egypt, we suggest that the use of sorafenib for the treatment of advanced HCC cases should be restricted to a highly selected subgroup of patients with good performance and child A.

Final analysis of GIDEON (Global Investigation of Therapeutic Decisions in Hepatocellular Carcinoma [HCC] and of Its Treatment with Sorafenib [Sor]) in >3000 Sor-treated patients (pts): Clinical findings in pts with liver dysfunction.

4126 Background: GIDEON is a prospective, non-interventional study. Completion of GIDEON creates a large, global database of >3000 Sor-treated unresectable HCC (uHCC) pts, allowing for evaluation of a broad pt population, including Child-Pugh (CP) B pts with more advanced liver dysfunction. Methods: Baseline characteristics were collected in pts for whom a decision to treat with Sor had been made in clinical practice. Adverse events (AEs), dosing, and outcomes data were collected during follow-up. Results: 3,202 pts were evaluable for safety. Overall, the incidence of AEs and drug-related (DR) AEs was similar across CP subgroups, although serious AEs (SAEs) were more common in CP-B than CP-A pts. The rate of DR AEs (event per patient-year) was also comparable between CP-A and CP-B pts. The average daily Sor dose was slightly higher in CP-B than CP-A pts; duration of treatment was longer in CP-A (Table). In the intent-to-treat population (n=3,213), median overall survival (OS) (months [95% CI]) was longer in CP-A (13.6 [12.8-14.7]) than CP-B pts (5.2 [4.6-6.3]); time to progression was similar: CP-A (4.7 [4.3-5.2]); CP-B (4.4 [3.5-5.5]). Median OS was shorter in pts with a higher CP-B score: 7 (6.2 [4.9-8.7]); 8 (4.8 [4.1-6.9]); 9 (3.7 [3.0-5.1]). Conclusions: Sor safety and dosing during treatment are generally consistent across pts irrespective of liver function. As anticipated, CP status is a strong prognostic factor for OS in uHCC pts. [Table: see text]

Effects of Hepatic Impairment on the Pharmacokinetics of Everolimus: A Single-Dose, Open-Label, Parallel-Group Study

BackgroundAlthough the pharmacokinetics of everolimus, an oral mammalian target of rapamycin inhibitor, have been characterized in patients with moderate hepatic impairment, they have not been assessed in those with mild or severe hepatic impairment. ObjectiveThe goal of this study was to assess the pharmacokinetics and safety of everolimus in healthy volunteers with normal hepatic function and patients with mild (Child-Pugh class A), moderate (Child-Pugh class B), and severe (Child-Pugh class C) hepatic impairment in otherwise good health to inform dosing in the clinical setting. MethodsA multicenter, open-label, Phase I study in which all enrollees received a single, 10-mg, oral everolimus dose was conducted. Blood samples for pharmacokinetic assessment were collected at predetermined time points up to 168 hours postdosing. Safety was also assessed. Proposed dose recommendations based on Child-Pugh status at baseline and day 8 were calculated based on AUC0–∞ geometric mean ratios and their associated 90% CIs. Post hoc analysis of the relationship between pharmacokinetic parameters and markers of hepatic function was also performed to identify thresholds for dose adjustment. ResultsThirteen subjects with normal hepatic function and 7 patients with mild, 8 patients with moderate, and 6 patients with severe hepatic impairment were enrolled. Compared with normal subjects, everolimus AUC0–∞ for patients with mild, moderate, and severe hepatic impairment increased by 1.60-, 3.26-, and 3.64-fold, respectively. Based on Child-Pugh classification at day 8, the everolimus doses required to adjust the exposure of patients with mild, moderate, and severe hepatic impairment to that of normal subjects were 6.25, 3.07, and 2.75 mg, respectively. Thresholds for 2-fold everolimus dose reduction were 15.0 μmol/L for bilirubin, 43.1 g/L for albumin, and 1.1 for the international normalized ratio; using these thresholds could lead to underdosing or overdosing in some patients. Most adverse events were of grade 1 severity, ≤1 day in duration, and not everolimus related. ConclusionsEverolimus exposure after a single 10-mg dose was influenced by the degree of hepatic impairment. Child-Pugh classification was found to be the most conservative means of guiding dose adjustment in patients with hepatic impairment. Based on these data, as well as previously reported data for patients with moderate hepatic impairment, everolimus once-daily dosing should be 7.5 mg and 5 mg in patients with mild and moderate impairment, respectively. Everolimus is not recommended in patients with severe hepatic impairment unless benefits outweigh risks; in that case, 2.5 mg once daily should not be exceeded. ClinicalTrials.gov identifier: NCT00968591.

Defining prognostic factors of survival after external beam radiotherapy treatment of hepatocellular carcinoma with lymph node metastases

To identify independent predictors of survival in patients with lymph node (LN) metastases from hepatocellular carcinoma (HCC) after external beam radiotherapy (EBRT). There were 191 patients with LN metastases from HCC received EBRT enrolled in the study cohort. EBRT was designed to focus on the LNs and a median dose of 50Gy (range 40-60Gy) was delivered. Treatment response was assessed by the WHO response criteria. Factors such as demographic data, tumor characteristics, and treatment modalities were determined before EBRT. Predictors of survival were identified by univariate and multivariate analysis. The median survival was 8.0months for all patients. Factors including Child-Pugh status (p=0.009), intrahepatic tumor control (p=0.015), LN location (p=0.015), and response to EBRT (p<0.001) were significant prognostic factors predicting for survival by multivariate analysis. The objective regression rate (ORR), which is the sum of complete and partial response rates, was as high as 79.1%. As determined by multivariate analysis, the factors of LN location near liver (p=0.002), smaller LN size (p=0.021), and higher EBRT dose (p<0.001) were associated with higher ORR values. This study provides detailed information about survival outcomes and prognostic factors. Child-Pugh B value, uncontrolled intrahepatic tumor, LN location far from liver, and no response to EBRT are the unfavorable independent predictors.

Serum Creatinine Levels Unrelated to Child-Pugh Status in Uncomplicated Cirrhosis of Liver with Ascites

Introduction: Liver cirrhosis and renal failure are two diseases that may occur in conjunction due to mutually related pathological processes. Liver cirrhosis causes portal hypertension that ultimately causes splanchnic vasodilatation leading to hepatorenal syndrome. Hypovolemia is another cause of renal failure in liver cirrhosis. The study presented here was done to assess the renal functions in patients with liver cirrhosis with ascites. Materials and methods: Sixty patients with uncomplicated cirrhosis of liver with ascites with normal renal function were included in this study. All patients were examined physically and biochemical. Main biochemical variables were serum bilirubin, serum albumin, serum creatinine and prothrombin time. Enrolled patients were categorized according to Child-Pugh class B and C. Serum creatinine levels were measured in all cases. Results: Mean level of serum albumin, serum creatinine and prothrombin time among Child B and C classes of liver cirrhosis patients were 27.36 vs 26.84 gm/dl, 0.79 vs 0.93 mg/dl, 15.97 vs 19.26 seconds respectively. No statistically significant change in the serum creatinine level among Child B and C were noticed. Conclusion: This study showed that the effect of liver cirrhosis on renal dysfunction would be minimal, if any.

Single-center Comparison of Three Chemoembolization Regimens for Hepatocellular Carcinoma

PurposeTransarterial chemoembolization regimens for hepatocellular carcinoma (HCC) vary, without a gold-standard method. The present study was performed to evaluate outcomes in patients with HCC treated with doxorubicin/ethiodized oil (DE), cisplatin/doxorubicin/mitomycin-c/ethiodized oil (CDM), or doxorubicin drug-eluting beads (DEBs). Materials and MethodsPatients received the same regimen at all visits, without crossover. Groups were compared based on Child–Pugh disease status, tumor/node/metastasis stage, and Barcelona Clinic Liver Cancer stage. Imaging outcomes were assessed based on modified Response Evaluation Criteria in Solid Tumors to calculate tumor response (ie, sum of complete and partial response), progressive disease (PD), and time to progression (TTP). ResultsA total of 228 infusions were performed in 122 patients: 59 with DE, 30 with CDM, and 33 with DEBs. The groups had similar Child–Pugh status (P = .45), tumor/node/metastasis stages (P = .5), and Barcelona Clinic Liver Cancer scores (P = .22). Follow-up duration was similar among groups (P = .24). Patients treated with DE underwent significantly more treatments (2.3±1.4) than those treated with CDM (1.6±0.7; P = .004) or DEBs (1.4±0.6; P<.0001). Compared with DE (51%), tumor response was significantly more common with CDM (84%; P = .003) or DEBs (82%; P = .004). PD was significantly more likely with DE (37%) than with CDM (13%; P = .02) or DEBs (9%; P = .004). TTP was similar between groups (P = .07). CDM and DEBs were similar in regard to disease progression (P = .6) and response (P = .83). ConclusionsDuring a similar follow-up period, patients treated with CDM or DEB chemoembolization showed a significantly higher response rate and a lower incidence of tumor progression, with fewer required treatment sessions, than those treated with DE chemoembolization.

Systematic review of outcomes of liver resection for early hepatocellular carcinoma within the Milan criteria

Long-term overall survival after liver resection in patients with hepatocellular carcinoma (HCC) within the Milan criteria has been reported to improve in recent years. This study systematically reviewed the outcomes of surgical resection for HCC in patients with good liver function and meeting the Milan criteria for early HCC, published in the past 10 years. A literature search was conducted in PubMed for papers on outcomes of surgical resection for HCC published between January 2000 and December 2010. Cochrane systematic review methodology was used for this review. The primary outcome was overall survival. Secondary outcomes included operative mortality and disease-free survival. Studies that focused on geriatric populations, paediatric populations, a subset of the Milan criteria (such solitary tumours) or included patients with incidental tumours were excluded, as were case reports, conference abstracts, and studies with a large proportion of Child-Pugh grade C liver cirrhosis or unknown Child-Pugh status. Of 152 studies reviewed, two randomized clinical trials and 27 retrospective case series were eligible for inclusion. The 5-year overall survival rate after resection of HCC ranged from 27 to 81 (median 67) per cent, and the median disease-free survival rate from 21 to 57 (median 37) per cent. There was a trend towards improved overall survival in recent years. The operative mortality rate ranged from 0 to 5 (median 0·7) per cent. Surgical resection offers good overall survival for patients with HCC within the Milan criteria and with good liver function, although recurrence rates remain high. Outcomes have tended to improve in more recent years.

Radioembolization for hepatocellular carcinoma with portal vein thrombosis: Impact of liver function on systemic treatment options at disease progression

Yttrium-90 ((90)Y) radioembolization is a microembolic procedure. Hence, it is commonly used in hepatocellular carcinoma (HCC) patients with portal venous thrombosis (PVT). We analyzed liver function, imaging findings, and treatment options (local/systemic) at disease progression following (90)Y treatment in HCC patients with PVT. We treated 291 HCC patients with (90)Y radioembolization. From this cohort, we included patients with liver-only disease, PVT and Child-Pugh (CP) score ≤ 7; this identified 63 patients with HCC and PVT (CP-A:35, CP-B7:27). Liver function, CP status, and imaging findings at progression were determined in order to assess potential candidacy for systemic treatment/clinical trials. Survival, time-to-progression (TTP), and time-to-hepatic decompensation analyses were performed using Kaplan-Meier methodology. Of 35 CP-A and 28 CP-B7 patients, 29 and 15 progressed, respectively. Median survival and TTP were 13.8 and 5.6 months in CP-A and 6.5 and 4.9 months in CP-B7 patients, respectively. Of the 29 CP-A patients who progressed, 45% maintained their CP status at progression (55% decompensated to CP-B). Of the 15 CP-B7 patients who progressed, 20% improved to CP-A, 20% maintained their CP score and 60% decompensated. Knowledge of liver function and CP score of HCC with PVT progressing after (90)Y is critically relevant information, as these patients may be considered for systemic therapy/clinical trials. If a strict CP-A status is mandated, our study demonstrated that 64% of cases exhibited inadequate liver function and were ineligible for systemic therapy/clinical trials. An adjuvant approach using local therapy and systemic agents prior to progression should be investigated.

Erratum

International Journal of Clinical PracticeVolume 66, Issue 9 p. 912-912 ERRATUMFree Access Erratum This article corrects the following: First interim analysis of the GIDEON (Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib) non-interventional study R. Lencioni, M. Kudo, S.-L. Ye, J.-P. Bronowicki, X.-P. Chen, L. Dagher, J. Furuse, J. F. Geschwind, L. L. de Guevara, C. Papandreou, A. J. Sanyal, T. Takayama, S. K. Yoon, K. Nakajima, F. Cihon, S. Heldner, J. A. Marrero, Volume 66Issue 7International Journal of Clinical Practice pages: 675-683 First Published online: June 15, 2012 First published: 17 August 2012 https://doi.org/10.1111/ijcp.12005AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Original paper “First interim analysis of the GIDEON (Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib) non-interventional study”. Int J Clin Pract 2012; 66: 675–683. A co-author’s name was incorrectly printed as L.L de Guevara. The correct name is L. Ladrón de Guevara. Also, in the results section, under sorafenib administration by Child-Pugh status, the sentence “Duration of treatment was generally shorter in Child-Pugh A than in Child-Pugh B patients.” should read “Duration of treatment was generally shorter in Child-Pugh B than in Child-Pugh A patients.” All other data in the paragraph, in the relevant table and the remainder of the paragraph are correct. Reference 1 Lencioni R, Kudo M, Ye S-L, Bronowicki J-P, Chen X-P, Dagher L, Furuse J, Geschwind JF, Ladrón de Guevara L, Papandreou C, Sanyal AJ, Takayama T, Yoon SK, Nakajima K, Cihon F, Heldner S, Marrero JA. First interim analysis of the GIDEON (Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib) non-interventional study. Int J Clin Pract 2012; 66: 675– 683. Volume66, Issue9September 2012Pages 912-912 ReferencesRelatedInformation

First interim analysis of the GIDEON (Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib) non-interventional study

Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib (GIDEON), a global, non-interventional, surveillance study, aims to evaluate the safety of sorafenib in all patients with unresectable hepatocellular carcinoma (uHCC) under real-life practice conditions, particularly Child-Pugh B patients, who were not well represented in clinical trials. Treatment decisions are determined by each physician according to local prescribing guidelines and clinical practice. Patients with uHCC who are candidates for systemic therapy, and for whom a decision has been made to treat with sorafenib, are eligible for inclusion. Demographic data and medical and disease history are recorded at entry. Sorafenib dosing and adverse events (AEs) are collected throughout the study. From January 2009 to April 2011, >3000 patients from 39 countries were enrolled. The prespecified first interim analysis was conducted when the initial approximately 500 treated patients had been followed up for ≥4 months; 479 were valid for safety evaluation. Preplanned subgroup analyses indicate differences in patient characteristics, disease aetiology and previous treatments by region. Variation in sorafenib dosing by specialty are also observed; Child-Pugh status did not appear to influence the starting dose of sorafenib. The type and incidence of AEs was consistent with findings from previous clinical studies. AE profiles were comparable between Child-Pugh subgroups. The GIDEON study is generating a large, robust database from a broad population of patients with uHCC. First interim analyses have shown global and regional differences in patient characteristics, disease aetiology and practice patterns. Subsequent planned analyses will allow further evaluation of early trends.

Clinical features of hepatocellular carcinoma in patients with autoimmune hepatitis in Japan

The occurrence of hepatocellular carcinoma (HCC) in patients with autoimmune hepatitis (AIH) is rare compared to that in patients with viral hepatitis. To clarify the status of HCC in patients with AIH in Japan, the clinical features of HCC in patients with AIH were analyzed. A primary survey gathered data from 496 member institutions of the Liver Cancer Study Group of Japan, and a secondary survey collected additional information from 250 HCC patients out of a total 4869 AIH patients who were identified in the primary survey. Of the 250 patients identified through the secondary survey, 127 patients (50.8 %) from throughout Japan were found to have HCC. The mean age at diagnosis of HCC was 69 years, and the male-to-female ratio was 1:5.7. The mean period from diagnosis of AIH to detection of HCC was 8 years, and Child-Pugh status at the time of HCC diagnosis was class A in 61.8 %; of the patients analyzed, 77.9 % also had cirrhosis of the liver. The mean value of maximum tumor diameter was 4.3 cm, and clinical stages were I in 20.1 % of patients, II in 47.6 %, III in 23.4 %, and IV in 8.9 %. The therapeutic modality used was surgery in 30.2 %, percutaneous therapy in 29.5 %, transcatheter arterial chemoembolization in 36.4 %. Cumulative survival rate was 85.4 % at one year. The survey results showed that HCC developed in 5.1 % of patients with AIH in Japan, with cirrhosis of the liver commonly found in elderly individuals; when HCC was diagnosed at an early clinical stage, in many cases, the liver function was relatively preserved. After diagnosis of AIH, observation of its progression with close attention to potential HCC complications is necessary.

Activity of Thalidomide and Capecitabine in Patients With Advanced Hepatocellular Carcinoma

Thalidomide has shown modest activity in advanced hepatocellular carcinomas (HCCs). Single-agent capecitabine has also been used in patients with HCC, with objective responses being reported. In our study, we review the use of thalidomide and capecitabine combination in advanced HCC. From November 2003 and September 2008, 42 patients with advanced HCC who were not eligible for clinical trial or conventional chemotherapy were treated with oral capecitabine (2000 mg/m/d) for 14 days every 3 weeks and oral thalidomide at the doses of 50 to 200 mg/d. Almost 50% of patients had Child-Pugh B or C liver cirrhosis and a history of regional or systemic therapy. Three patients achieved complete responses lasting more than 52 weeks, including 1 patient who achieved pathological complete response and underwent curative resection. There were 3 patients with partial responses and 13 with stable disease. Median overall survival of all 42 patients was 9.9 months. The median progression-free survival was 5.1 months. The presence of ascites, portal vein thrombosis, and poorer Child-Pugh liver cirrhosis status also resulted in significantly poorer survival outcome. Treatment was well tolerated. Fatigue was the most common side effect occurring in 16 (38%) patients, but only 1 patient had grade 3 toxicity and had to stop treatment. Two other patients developed grade 3 palmar-plantar erythrodysesthesia from capecitabine. The combination of thalidomide and capecitabine has activity in advanced HCC and can result in complete pathological response. Treatment is well tolerated even in less-fit patients who have been pretreated and deserve further study.

Predictors for survival in hepatocellular carcinoma.

e14640 Background: The global incidence of HCC is over 700,000 patients making it the sixth leading cancer and the prognosis is poor with a 5 year survival of 11%. It is important to understand if there are differences in survival based on the presence of Hepatitis B or C or alcohol cirrhosis, ethnicity and/or treatments employed in various stages of the disease. Methods: A robust global retrospective study of HCC patients was conducted with nearly 4,000 patient records from US, Germany, France, Spain, Italy, China and South Korea in 2011. Of these nearly 800 included deceased patients. These records were analyzed to study if any known factors such as ethnicity, presence of Hepatitis B, Hepatitis C or alcohol cirrhosis and/or treatments used at diagnosis could serve as predictors for survival. Kaplan-Meier curves were plotted to understand the differences in survival based on ethnicity, Child-Pugh status and treatments employed at various stages. Results: One year survival is lower in China/ Korea compared to US and EU, however, five year survival rates are comparable across regions. Associated hepatitis or cirrhosis does not convey any differences in one year survival whether patients received sorafenib as first line treatment or not. Statistically significant higher one year survival rates are observed for HCC patients in Europe and USA receiving transarterial chemoembolization (TACE) compared with patients receiving sorafenib first line. However, in China and Korea there is no such difference. Across all three regions: USA, EU and Asia there is no difference in survival in stage IV patients receiving sorafenib or no sorafenib. No significant differences in one year survival are seen in USA, EU and Asia for patients with Hepatitis C or B or cirrhosis compared to those with no history of liver disease. The Child-Pugh C patients had lower survival compared to Child-Pugh A or B patients. Conclusions: Early diagnosis of HCC, early intervention and treatment appear to show survival benefits as opposed to drug treatment with sorafenib initiated in the later stages of the disease. Efforts should increase for screening, early detection and treatment initiation at early stage to improve outcomes in HCC patients.

The use of single‐agent sorafenib in the treatment of advanced hepatocellular carcinoma patients with underlying Child‐Pugh B liver cirrhosis

This study explored the efficacy, tolerability, and survival benefits of using sorafenib in patients with Child-Pugh class B (CPB) cirrhosis. Patients with advanced hepatocellular carcinoma who were treated with sorafenib at Queen Mary Hospital, Hong Kong, China, were analyzed retrospectively. Treatment outcomes were analyzed according to their respective Child-Pugh status. Patients with CPB disease were further divided into CPB7 (those with a score of 7) and CPB8-9 (a score of 8 or 9) subgroups. The baseline demographic parameters were comparable between 108 patients with Child-Pugh class A (CPA) disease and 64 CPB patients. Both clinical benefit rate (21.3% vs 32.4% vs 14.8%; P = .23) and progression-free survival (median: 3.2 months vs 3.2 months vs 2.3 months; P = .26) were similar among CPA, CPB7, and CPB8-9 groups, respectively. The overall survival was different among these groups (P = .002) and showed a trend toward worse outcome in CPB patients: the median was 6.1, 5.4, and 2.7 months among CPA, CPB7, and CPB8-9 patients, respectively. The commonest grade 3/4 adverse events were hand-foot syndrome (13.5%), diarrhea (9.9%), and rash (7.0%). Grade 3/4 leukopenia, thrombocytopenia, and anemia occurred in 2.9%, 5.3%, and 8.8% of the patients, respectively. Overall, the 3 groups of patients experienced similar incidence of most of these adverse events. Nonetheless, CPB patients experienced more anemia (P = .01), gastrointestinal bleeding (P = .02), and hepatic encephalopathy (P = .02). CPA and CPB patients tolerated sorafenib similarly and derived similar clinical and progression-free survival benefit. Among CPB patients, most benefits were observed in patients with a score of 7. Nevertheless, CPB patients were more susceptible to developing cirrhotic complications, and thus more vigilant surveillance is needed.

Treatment of an elderly patient with hepatocellular carcinoma: Counseling from the patient's point of view

showed that older recipient age is associated with lowerposttransplant survival rates. These investigatorsdeveloped an older recipient prognostic score using 5factors: ventilator status, diabetes mellitus, hepatitis Cvirus, creatinine levels 1.6 mg/dL, and combinedrecipient and donor age 120 years. When the olderrecipient prognostic score was >2 points, the 5-yearsurvival rate was less than 50% (typically a barrierindicating a futile liver transplant). Lipshutz et al.

Second interim analysis of the Global Investigation of Therapeutic Decisions in Unresectable HCC and of Its Treatment with Sorafenib (GIDEON): Sorafenib dosing and safety in U.S. patients.

302 Background: Sorafenib (SOR) is the first systemic therapy to improve survival in patients (pts) with advanced hepatocellular carcinoma (HCC). GIDEON is a global, prospective, noninterventional study to evaluate SOR safety in pts with unresectable HCC in real-life practice. We present results from the second interim analysis, describing SOR dosing in US pts. Methods: From Jan 2009 – Nov 2010, 326 pts were enrolled in 92 US centers and followed ≥4 months, with 313 pts evaluable for safety. Demographics, initial dose, treatment duration (TD), dose modifications (mods), treatment interruptions (TIs), and adverse events (AEs) were analyzed in pts with complete data available. Results: Initial SOR dose was 400 mg/d in 106 pts (34%) and 800 mg/d in 177 pts (57%). Thirty (10%) pts received alternate doses or had incomplete data. Most pts were male (400 mg/d: 75%; 800 mg/d: 80%). Age distribution was similar between groups (400 mg/d: 59% &lt;65 yr and 41% &gt;65 yr; 800 mg/d: 64% &lt;65 yr and 36% &gt;65 yr). In 400 mg/d vs 800 mg/d groups respectively, ECOG PS was 0/1/2 in 19%/49%/16% vs 34%/35%/12%, and Child-Pugh (CP) status was A/B/C in 32%/35%/7% (26% unevaluable) vs 42%/29%/6% (21% unevaluable). Median TD was 9.8 wks (&lt;4 wks in 22%, &gt;4-12 wks in 40%, and &gt;12 wks in 39%) in the 400 mg/d group and 13.2 wks (&lt;4 wks in 17%, &gt;4-12 wks in 29%, and &gt;12 wks in 53%) in the 800 mg/d group. Dose mods and TIs occurred in 49% (37% due to AE) and 35%, and 57% (36% due to AE) and 38% of 400 mg/d vs 800 mg/d pts, respectively. See table for safety data. Conclusions: While statistical comparisons were not made, PS or CP status may impact initial SOR dose selection. Other baseline characteristics did not affect this decision. Frequencies of dose mods, TIs, and AEs were similar between dosing groups. Limitations of an observational study must be considered. Clinical judgment remains important in choosing initial SOR dose. [Table: see text]

Patients with liver cancer suitable for sorafenib evaluation registry (LIVER) in Poland.

194 Background: Due to chronic hepatitis and cirrhosis as main risk factors of HCC – patients in Poland can be treated either by oncologists or by gastroenterologists. As no data exist on HCC patient flow between these specialities, this registry was set up. We also wanted to know the differences in both specialities’ approach to targeted therapies. Methods: Data of patients treated by oncologists (LIVER 2) and gastroenterologists (LIVER 1) were recorded. Descriptive statistical methods and U-Mann-Whitney and Fisher tests were used. Results: 478 patients were included into registry from 2009 until the end of 2010. 70% of patients were male. In 42% cases HCC was caused by HCV and in 24% by HBV. LIVER 2 recorded more patients with unknown HCC aetiology than LIVER 1 (35% vs 15%). The HCC diagnosis was made based on CT scan (80%, ns), US scan (74% in LIVER 1 vs 47% in LIVER 2, p&lt;0,0001) or biopsy (72% LIVER 2 vs 48% LIVER 1, p&lt;0,0001). Patients with advanced stage of HCC according to BCLC scale and poor performance status were more frequently seen by oncologists (LIVER 2), similar prevalence in Child Pugh status was observed in both groups (p&lt;0,05 for all). Registry showed differences in frequency of extrahepatic lesions (10% LIVER 1 42% in LIVER 2, p&lt;0,05). Most common co morbidities were diabetes (32%), liver disorders (39%), hypertension (61%), coronary disease (24%). Median AFP level was 100 ng/ml in LIVER 1 and 219 in LIVER 2 (p=0,057). Registry showed that for gastroenterologists reasons to consider sorafenib as next step in therapy was in 47% cases HCC progression, in 51% good performance status and in 55% sorafenib was found as the only one therapy suitable due to contraindications for other treatments. Oncologists consider sorafenib therapy in 56% cases due to HCC progression and in 72% cases due to good performance status. Among patients considered for targeted therapy, approximately 20% presented Child Pugh B status. Conclusions: This is the first detailed HCC registry in Poland covering the different therapeutic area specialists. Patients with more advanced HCC and worse performance status are more frequently treated by oncologists (p&lt;0,05). The data shows need of early HCC detection interdisciplinary system referring patients to the oncologist.

Second interim analysis of GIDEON (Global Investigation of Therapeutic Decisions in Unresectable HCC and of Its Treatment with Sorafenib): U.S. versus global perspective on patient and disease characteristics, treatment history, and sorafenib use.

278 Background: GIDEON is a global, prospective, noninterventional study of patients (pts) treated with sorafenib (SOR) for unresectable hepatocellular carcinoma (uHCC). Regions evaluated included US, Europe, Japan, Asia Pacific, and Latin America. Detailed regional data were presented by Kudo et al (ILCA 2011, abstr 0-030). Data from the second US interim analysis are compared to global results. Methods: Eligible pts had uHCC and were treated with SOR. Demographics, disease etiology, treatment history, and SOR dosing were compared in a descriptive, preplanned subgroup analysis. Results: Global and US safety populations comprised 1571 and 313 pts, respectively. In the US, hepatitis B was less common (18% vs 37% global) whereas hepatitis C was more frequent (53% vs 32% global). Alcoholic liver disease etiology was higher in US pts (41% vs 29% global). US pts were diagnosed with later-stage disease, but fewer US pts had documented BCLC and Child-Pugh status. Fewer US pts had an ECOG PS 0 at start of SOR (28% vs 40% global). Rates of prior surgery and locoregional treatment were similar in US (11% and 49%, respectively) and global pts (19% and 55%, respectively). US pts treated with TACE (n = 116) underwent fewer TACE procedures (≥3: 13.8% vs 38.9% global); most (59%) TACE-treated pts in the US received 1 treatment. In US vs global pts, median time from prior surgery to start of SOR was 10 months (range 1-61) vs 14 months (range 1-181) and median time from last TACE to start of SOR was 3.2 months vs 3.1 months. Conclusions: Disease characteristics and treatment patterns for pts with uHCC in the US differ from those in the global population. US pts enrolled in GIDEON (ie, receiving SOR) have differing etiologies of liver disease and have a greater proportion of hepatic dysfunction, likely accounting for worse performance status. [Table: see text]

Second interim analysis of GIDEON (Global Investigation of Therapeutic Decisions in Unresectable HCC and of Its Treatment with Sorafenib): Sorafenib treatment and safety in U.S. patients with Child-Pugh B status.

282 Background: Sorafenib (SOR) is the first systemic therapy to demonstrate a survival benefit in patients (pts) with late-stage hepatocellular carcinoma (HCC). GIDEON is an ongoing, global, prospective, noninterventional study of HCC pts receiving SOR in real-life practice. We present results from the second interim analysis, describing dosing and safety of SOR in HCC pts with Child-Pugh (CP)-B status in the US. Methods: From Jan 2009 – Nov 2010, 326 pts were enrolled (n = 313, safety population) and followed ≥4 months at 92 US centers. Eligible pts had unresectable HCC and were treated with SOR. Demographics, initial dose, treatment duration (TD), dose modifications (mods), and adverse events (AE) were analyzed in pts with available CP status. Results: 119 (38%) pts were CP-A and 100 (32%) were CP-B. 94 (30%) pts were excluded (Table). Median (med) SOR dose was 580 mg/d in CP-A pts and 577 mg/d in CP-B pts. Med TD was 14.4 weeks (wks) in CP-A pts and 10.1 wks in CP-B pts. TD was &lt;4 wks, 4-12 wks, and &gt;12 wks in 14%, 29%, and 56% of CP-A pts, and 22%, 36%, and 39% of CP-B pts, respectively. Treatment-emergent (TE) drug-related AE (all grades) were similar between groups, but more CP-B pts discontinued SOR due to AE (Table). In CP-A and -B pts, all-grade AE were as follows: hand-foot skin reaction (HFSR) (28% vs 19%), diarrhea (28% vs 27%), and fatigue (15% vs 16%). All-grade elevations in ALT, AST, and bilirubin were 2.5%, 2.5%, and 3.4% in CP-A pts and 3%, 1%, and 4% in CP-B pts. Conclusions: These interim US data suggest that SOR safety may be similar in HCC pts with CP-A and CP-B status. Med SOR dose was similar, but med TD was shorter in CP-B pts. AEs were as expected, although HFSR may be underreported in CP-B pts. Limitations of an observational registry must be considered. [Table: see text]

Experience with sorafenib treatment of hepatocellular carcinoma (HCC) in patients in a Brazilian center.

350 Background: HCC is the most important cause of death in patients with liver cirrhosis. Sorafenib is established as treatment for patients with compensated liver disease, but there are few studies for patients with more advanced cirrhosis. Methods: From May 2008, 75 patients intermediate - advanced (according to BCLC) HCC patient initiated sorafenib at 800 mg daily doses, 71 were treated or had been treated for more than 1 month and were recruited to data analysis on August 2011, regarding sex, age, association with diabetes, etiology of cirrhosis, treatment intervals, dose reductions, adverse events, response rates, Child-Pugh’s classification, global survival and survival according Child-Pugh status Results: The median age of study population of 75 patients (60 men and 15 women) was 63,78 years. The cirrhosis etiology was 46% VHC, 13% N.AS.H, 10,71% cryptogenic cirrhosis and 6.15% with VHB. 40% of the patients were Child A, 41.5% B and 10.8% C . 34% were diabetic, the median treatment interval of sorafenib was 223 days (7-1080 days); Overall response rate was 66%: 37.5 % had stable disease and 25% had partial response with tumor shrinkage by Recist criteria. Adverse events were related in 53.84 % of the patients and 60 % of them needed to have dose modifications. The common adverse events were diarrhea: 48.5%, nausea and vomiting: 31.4 %, abdominal pain: 45.7%, hand-foot syndrome 25.7%, arterial hypertension 8.5% and 8.5 % bleeding. The incidence of adverse events didn’t differ considering each Child-Pugh’s subgroup. The median survival time was 12.1 months. The one and two year survival preliminary rate were 75 % and 68% in Child-Pugh A patients and 40 and 10 % in Child-Pugh B patients (p=0.002) respectively. Conclusions: Our results contributed to emphasize treatment safety of sorafenibe within Hcc patients with more advanced liver disease. In this study population, 52.7% of the patients had liver disease Child B/C and sorafenib was well tolerated (53 % had adverse events) in all subgroups with acceptable response and treatment intervals despite of advanced liver disease, but the survival rates trends to be statistically higher in patients with Child A than Child B.