Usefulness of alpha-fetoprotein response in patients treated with sorafenib for advanced hepatocellular carcinoma

Personeni, Nicola; Bozzarelli, Silvia; Pressiani, Tiziana; Rimassa, Lorenza; Tronconi, Maria Chiara; Sclafani, Francesco; Carnaghi, Carlo; Pedicini, Vittorio; Giordano, Laura; Santoro, Armando

doi:10.1016/j.jhep.2012.02.016

Cited by 197 publications

(182 citation statements)

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“…Park et al [18] reported that AFP and DCP response were independent factors associated with survival. Personeni et al [17] reported that AFP response is an independent surrogate end point for survival in patients treated with sorafenib. Similarly, a ≥ 50% decline in AFP and PIVKA-Ⅱ after the second cycle of HAIC treatment was associated with better outcomes among the patients with elevated AFP and PIVKA-Ⅱ levels prior to the initiation of HAIC treatment (though PIVKA-Ⅱ reduction is not statistically significant by multivariate analysis) (Figure 4).…”

Section: Discussionmentioning

confidence: 99%

“…The patient's liver function was classified according to the scheme of Child-Pugh. AFP and PIVKA-Ⅱ reduction were calculated according to the formula [(baseline levellevel after the second cycle)/(baseline level) × 100] in patients whose AFP was elevated above 20 ng/mL [17] and PIVKA-Ⅱ was elevated above 40 mAU/mL [18] . The treatment toxicity was assessed using the Common Terminology Criteria for Adverse Events (CTCAE) v. 4.0 [19] .…”

Section: Study Assessmentmentioning

confidence: 99%

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Hepatic arterial infusion chemotherapy in hepatocellular carcinoma with portal vein tumor thrombosis

Song

Bae²,

Song³

et al. 2013

WJG

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AIM:To evaluate the prognostic factors and efficacy of hepatic arterial infusion chemotherapy in hepatocellular carcinoma with portal vein tumor thrombosis. METHODS:Fifty hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) were treated using hepatic arterial infusion chemotherapy (HAIC) via a subcutaneously implanted port. The epirubicin-cisplatin-5-fluorouracil (ECF) chemotherapeutic regimen consisted of 35 mg/m 2 epirubicin on day 1, 60 mg/m 2 cisplatin for 2 h on day 2, and 500 mg/m 2 5-fluorouracil for 5 h on days 1-3. The treatments were repeated every 3 or 4 wk. RESULTS:Three (6%) of the 50 patients achieved a complete response (CR), 13 (26%) showed partial responses (PR), and 22 (44%) had stable disease (SD).The median survival and time to progression were 7 and 2 mo, respectively. After 2 cycles of HAIC, CR was achieved in 1 patient (2%), PR in 10 patients (20%) and SD in 26 patients (52%). Significant pre-treatment prognostic factors were a tumor volume of < 400 cm 3 (P = 0.01) and normal levels of protein induced by vitamin K absence or antagonist (PIVKA)-Ⅱ (P = 0.022). After 2 cycles of treatment, disease control (CR + PR + SD) (P = 0.001), PVTT response (P = 0.003) and α-fetoprotein reduction of over 50% (P = 0.02) were independent factors for survival. Objective response (CR + PR), disease control, PVTT response, and combination therapy during the HAIC were also significant prognostic factors. Adverse events were tolerable and successfully managed. CONCLUSION: HAIC may be an effective treatment modality for advanced HCC with PVTT in patients with tumors < 400 cm 3 and good prognostic factors.© 2013 Baishideng. All rights reserved. Key words: Hepatocellular carcinoma; Hepatic arterial infusion chemotherapy; Portal vein tumor thrombosisCore tip: The aim of this study was to investigate the prognostic factors of hepatic arterial infusion chemotherapy in advanced hepatocellular carcinoma patients with portal vein tumor thrombosis. The primary findings of this study were as follows: (1) The median survival and time to progression were 7 and 2 mo, respectively; (2) A tumor volume of < 400 cm 3 and protein induced by vitamin K absence or antagonist-Ⅱ were independent pre-treatment prognostic factors; (3) Disease control and ≥ 50% tumor marker reduction were significant prognostic factors after the second cycle of hepatic arterial infusion chemotherapy (HAIC); and (4) Objective tumor response, disease control and portal vein tumor thrombosis response were independent post-treatment prognostic factors at the end of the HAIC. ORIGINAL ARTICLE

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Section: Discussionmentioning

confidence: 99%

Section: Study Assessmentmentioning

confidence: 99%

Hepatic arterial infusion chemotherapy in hepatocellular carcinoma with portal vein tumor thrombosis

Song

Bae²,

Song³

et al. 2013

WJG

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“…Other recent studies have investigated plasma biomarkers as potential markers of response to sorafenib (and other antiangiogenic therapies), such as α-fetoprotein [52][53][54][55], and additional research is ongoing. There are also some small studies that suggest that sorafenib AEs (e.g., skin toxicity and hypertension) may be markers of clinical efficacy and that the pattern of disease progression on sorafenib treatment may predict the postprogression prognosis [27,56].…”

Section: Identifying Markers Of Tumor Response May Help To Guide Soramentioning

confidence: 99%

Refining Sorafenib Therapy: Lessons from Clinical Practice

et al. 2014

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AbstrAct:Understanding the best use of sorafenib is essential in order to maximize clinical benefit in hepatocellular carcinoma. Based on Phase III and noninterventional study data, as well as our extensive experience, we discuss dose modification in order to manage adverse events, disease response evaluation and how to maximize treatment benefit. Sorafenib should be initiated at the approved dose (400 mg twice daily) and reduced/ interrupted as appropriate in order to manage adverse events. Dose modification should be considered before discontinuation. Appropriate tumor response assessment is critical. Focusing on radiologic response may result in premature sorafenib discontinuation; symptomatic progression should also be considered. If second-line therapies or trials are unavailable, continuing sorafenib beyond radiologic progression may provide a clinical benefit. Our recommendations enable the maximization of treatment duration, and hence clinical benefit, for patients. Keywords:• adverse event managementIt is well established that hepatocellular carcinoma (HCC) is a complex and heterogeneous disease that is affected by multiple genetic and epigenetic alterations [1]. In the overwhelming majority of patients, liver cirrhosis -another complex disease in its own right -is superimposed on HCC. As a result, the prognostic range for these patients varies considerably and continues to change for each patient at every time point over the clinical course of their disease. A meta-analysis of 30 clinical trials into which HCC patients were enrolled for palliative treatment reflects this heterogeneity. It demonstrated a high variability in survival among untreated patients and concluded that no single patient characteristic alone could predict outcome [2].The prognosis and treatment options for HCC are generally related to tumor stage and liver function at presentation [3,4]. In the west, approximately 30% of all patients with HCC are diagnosed in

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“…In addition, the AFP level has been considered as an important predictor of postoperative HCC recurrence and metastasis (20,21). In patients with advanced HCC treated with either sorafenib, transarterial chemoembolization, hepatic artery infusional chemotherapy or concurrent chemoradiotherapy, an early reduction of AFP was found to be a predictor of positive outcome (22)(23)(24)(25). Furthermore, the early elevation of AFP was shown to be a predictor of unfavorable outcome in patients with advanced HCC treated with sorafenib (26).…”

Section: Discussionmentioning

confidence: 98%

GALNT14 genotype, α-fetoprotein and therapeutic side effects predict post-chemotherapy survival in patients with advanced hepatocellular carcinoma

Lin

Hsu

Chen

et al. 2014

Molecular and Clinical Oncology

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Abstract. In addition to targeted agents, chemotherapy is currently considered to be a treatment option for patients with advanced hepatocellular carcinoma (HCC); however, it is associated with severe side effects that may limit its clinical use. UDP-N-acetyl-α-D-galactosamine:polypep tide N-acetyl-galactosaminyltransferase 14 (GALNT14) genotype was previously identified as a prognostic marker for HCC patients receiving 5-fluorouracil, mitoxantrone and cisplatin (FMP) combination chemotherapy. The present study aimed to assess clinical parameters and on-treatment side effects as effective predictors for favorable prognosis. A total of 118 patients with HCC receiving split-dose FMP were retrospectively enrolled. The clinical parameters, side effects and GALNT14 genotype were analyzed. The independent predictors for time-to-progression (TTP) and overall survival (OS) were assessed using Cox proportional hazards models. Following categorization, the Kaplan-Meier method was used to compare survival outcomes. Pretreatment α-fetoprotein (AFP) ≤2,800 ng/ml (median level), GALNT14 'TT' genotype, on-treatment leukopenia and absence of vomiting were identified as independent predictors of a favorable TTP (P= 0.001, 0.035, 0.008 and 0.009, respectively) and OS (P= 0.028, 0.006, 0.027 and 0.013, respectively). A total of 59 patients with AFP ≤2,800 ng̸ml exhibited longer median TTP and OS (3.11 vs. 1.75 months, P<0.001; and 8.14 vs. 3.79 months, P<0.001, respectively). A total of 30 patients with the GALNT14 'TT' genotype exhibited longer median TTP and OS (3.11 vs. 2.11 months, P= 0.014; and 5.75 vs. 3.93 months, P=0.001, respectively). Finally, 9 patients (9/118; 7.6%) with all four favorable factors exhibited the longest median TTP and OS (10.64 vs. 2.07 months, P= 0.002; and 25.50 vs. 4.50 months, P<0.001, respectively). In conclusion, the AFP level and the GALNT genotype may be considered as pre-therapeutic predictors of a favorable response. When combined with on-treatment leukopenia and absence of vomiting, a subgroup of patients with excellent outcome may be identified.

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Usefulness of alpha-fetoprotein response in patients treated with sorafenib for advanced hepatocellular carcinoma

Cited by 197 publications

References 27 publications

Hepatic arterial infusion chemotherapy in hepatocellular carcinoma with portal vein tumor thrombosis

Hepatic arterial infusion chemotherapy in hepatocellular carcinoma with portal vein tumor thrombosis

Refining Sorafenib Therapy: Lessons from Clinical Practice

GALNT14 genotype, α-fetoprotein and therapeutic side effects predict post-chemotherapy survival in patients with advanced hepatocellular carcinoma

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