Early increase in α-fetoprotein for predicting unfavorable clinical outcomes in patients with advanced hepatocellular carcinoma treated with sorafenib

Nakazawa, Takahide; Hidaka, Hiroyoshi; Takada, Juichi; Okuwaki, Yusuke; Tanaka, Yoshiaki; Watanabe, Masaaki; Shibuya, Akitaka; Minamino, Tsutomu; Kokubu, Shigehiro; Koizumi, Wasaburo

doi:10.1097/meg.0b013e32835d913b

Cited by 76 publications

(65 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Prospective phase Ⅲ trial [126] CEC/ CECP al [74] did not find a significant link between pretreatment AFP levels and tumor response in patients with advanced HCC treated with sorafenib. However, an early increase in AFP levels correlates with poorer outcome with shorter OS and PFS [74] .…”

Section: Poorer Prognosismentioning

confidence: 88%

“…However, an early increase in AFP levels correlates with poorer outcome with shorter OS and PFS [74] . Japanese groups proposed the lens culinaris agglutinin reactive AFP (AFP-L3), an isoform of AFP, as a good diagnostic and prognostic biomarker for HCC [75][76][77] .…”

Section: Poorer Prognosismentioning

confidence: 99%

“…Better TTP Better OS Nakazawa et al [74] 59 Retrospective Sorafenib AFP response (increase from baseline within four weeks)…”

Section: Poorer Dfs Higher Vascular Invasionmentioning

confidence: 99%

See 2 more Smart Citations

Evaluation of antiangiogenic efficacy in advanced hepatocellular carcinoma: Biomarkers and functional imaging

Bouattour

Payancé

Wassermann

2015

WJH

View full text Add to dashboard Cite

Many years after therapeutic wilderness, sorafenib finally showed a clinical benefit in patients with advanced hepatocellular carcinoma. After the primary general enthusiasm worldwide, some disappointments emerged particularly since no new treatment could exceed or at least match sorafenib in this setting. Without these new drugs, research focused on optimi zing care of patients treated with sorafenib. One challenging research approach deals with identifying prognostic and predictive biomarkers of sorafenib in this population. The task still seems difficult; however appropriate investigations could resolve this dilemma, as observed for some malignancies where other drugs were used.

show abstract

Section: Poorer Prognosismentioning

confidence: 88%

Section: Poorer Prognosismentioning

confidence: 99%

See 1 more Smart Citation

Evaluation of antiangiogenic efficacy in advanced hepatocellular carcinoma: Biomarkers and functional imaging

Bouattour

Payancé

Wassermann

2015

WJH

View full text Add to dashboard Cite

show abstract

“…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

View full text Add to dashboard Cite

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

show abstract

“…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). In addition, it was demonstrated that a low serum AFP level (≤50 ng/ml) was a favorable predictor for patients treated with intravenous 5-fluorouracil and subcutaneous recombinant interferon-α-2b (27), suggesting a predictive value of AFP in patients receiving chemotherapy.…”

Section: Discussionmentioning

confidence: 97%

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

View full text Add to dashboard Cite

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.

show abstract

Early increase in α-fetoprotein for predicting unfavorable clinical outcomes in patients with advanced hepatocellular carcinoma treated with sorafenib

Abstract: Early increase in AFP predicted PD and poorer survival and may thus be a useful biomarker in patients with advanced HCC who receive sorafenib.

Cited by 76 publications

References 33 publications

Evaluation of antiangiogenic efficacy in advanced hepatocellular carcinoma: Biomarkers and functional imaging

Evaluation of antiangiogenic efficacy in advanced hepatocellular carcinoma: Biomarkers and functional imaging

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

Contact Info

Product

Resources

About