Skin toxicity predicts efficacy to sorafenib in patients with advanced hepatocellular carcinoma

Shomura, Masako; Kagawa, Tatehiro; Shiraishi, Koji; Hirose, Shunji; Arase, Yoshitaka; Koizumi, Jun; Mine, Tetsuya

doi:10.4254/wjh.v6.i9.670

Cited by 30 publications

(26 citation statements)

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“…The severe adverse effects associated with sorafenib use, reported to occur in 50 % of patients [22], potentially influence HRQOL. Interestingly, skin toxicity [23], hypertension [24], and diarrhea [25] are known to be associated with better prognosis in sorafenib therapy. Therefore, the substantial anti-tumor effects of sorafenib might have countered severe adverse effects both physically and mentally.…”

Section: Discussionmentioning

confidence: 99%

Longitudinal alterations in health-related quality of life and its impact on the clinical course of patients with advanced hepatocellular carcinoma receiving sorafenib treatment

et al. 2016

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BackgroundThis study aimed to identify the health-related quality of life (HRQOL) domains associated with prognosis by assessing longitudinal alterations in HRQOL in patients with advanced hepatocellular carcinoma receiving sorafenib.MethodsWe prospectively assessed HRQOL by administering the SF-36 questionnaire 3-monthly to consecutive patients with advanced hepatocellular carcinoma receiving sorafenib. We evaluated the impact of HRQOL on their overall survival and duration of treatment with sorafenib using Cox's proportional hazards model.ResultsThere were 54 participants: 42 (78 %) were male, the median age was 71 years, 24 (44 %) had hepatitis C virus infection, 33 (61 %) had Child-Pugh scores of 5, and 30 (56 %) had TNM stage IV hepatocellular carcinoma. The median overall survival and treatment duration were 9 and 5 months, respectively, and 40 patients (74 %) died. Thirteen patients receiving sorafenib over a 1-year period maintained all domain scores >40, without a significant decline during the treatment period. In contrast, physical functioning, physical role, and vitality scores declined continuously and significantly in the year before death (in the 40 patients who died). Previous curative treatment and physical functioning scores ≥40 at baseline were significantly associated with longer overall survival by multivariate analysis. Social functioning scores ≥40, absence of vascular invasion, and lower DCP value were significant predictors of longer treatment duration.ConclusionsHRQOL was not significantly impaired in those patients who were able to complete a 1-year course of sorafenib treatment. Baseline physical functioning scores ≥40 and social functioning scores ≥40 were significantly associated with longer overall survival and longer treatment duration, respectively. Thus, HRQOL could be a valuable marker to predict the clinical course of patients with advanced hepatocellular carcinoma receiving sorafenib.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2908-7) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Longitudinal alterations in health-related quality of life and its impact on the clinical course of patients with advanced hepatocellular carcinoma receiving sorafenib treatment

et al. 2016

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“…Some retrospective studies have shown in patients with advanced HCC treated with sorafenib a positive association with early skin drug-related toxicities and clinical benefit [42][43][44] and disease control [44,45] (Table 4). Recently, the Barcelonan group reported the results of a prospective single-arm, monocentric study that assessed the link between early sorafenib-related skin toxicities and outcome in patients with advanced HCC [46] .…”

Section: Clinical Biomarkersmentioning

confidence: 99%

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

Bouattour

Payancé

Wassermann

2015

WJH

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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.

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“…Phase II and III trials in multiple tumor types have confirmed that nintedanib treatment is not associated with HFSR . However, HFSR is common during treatment with sorafenib, and it has been suggested that the presence of skin toxicity, including HFSR, may be a surrogate biomarker for sorafenib clinical efficacy . Hand–foot skin reaction can be severe, necessitating dose reductions or treatment discontinuation, and is thus a treatment concern .…”

Section: Discussionmentioning

confidence: 99%

“…(26,(28)(29)(30) However, HFSR is common during treatment with sorafenib, (8) and it has been suggested that the presence of skin toxicity, including HFSR, may be a surrogate biomarker for sorafenib clinical efficacy. (31,32) Hand-foot skin reaction can be severe, necessitating dose reductions or treatment discontinuation, and is thus a treatment concern. (8,31) There is speculation that sorafenibrelated HFSR may be due to the combined inhibition of several receptors, (33) specifically VEGFR, PDGFR, c-KIT, and Flt-3.…”

Section: Discussionmentioning

confidence: 99%

Phase I study of nintedanib in Japanese patients with advanced hepatocellular carcinoma and liver impairment

et al. 2016

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This phase I, dose‐escalation study evaluated the safety, preliminary efficacy and pharmacokinetics of nintedanib, a triple angiokinase inhibitor, in Japanese patients with advanced hepatocellular carcinoma and mild/moderate liver impairment. Thirty patients with unresectable hepatocellular carcinoma were enrolled to groups, depending on whether liver impairment was mild (group I, aspartate aminotransferase and alanine aminotransferase ≤2× upper limit of normal and Child–Pugh score 5 [n = 14] or 6 [n = 2]) or moderate (group II, Child–Pugh score 5–6 and aspartate aminotransferase or alanine aminotransferase >2× to ≤5× upper limit of normal [n = 7] or Child–Pugh score 7 [n = 7]); 22 patients had prior sorafenib treatment. Nintedanib was given twice daily in 28‐day cycles until disease progression or unacceptable adverse events, starting at 150 mg (group I) or 100 mg (group II) and escalating to 200 mg. The primary objective was to define the maximum tolerated dose based on occurrence of dose‐limiting toxicities during cycle 1 (grade ≥3 non‐hematological and grade 4 hematological adverse events). No dose‐limiting toxicities were reported during cycle 1 and the maximum tolerated dose for both groups was 200 mg twice daily. The most frequent adverse events were gastrointestinal (diarrhea, nausea, vomiting, and decreased appetite). No patients discontinued nintedanib due to adverse events; 31% of group I and 21% of group II had dose reductions. Median time to progression was 2.8 months (95% confidence interval, 1.05–5.52) for group I and 3.2 months (95% confidence interval, 0.95–6.70) for group II. Nintedanib showed a manageable safety profile and efficacy signals, including in patients previously treated with sorafenib. Clinical trial registration NCT01594125; 1199.120 (ClinicalTrials.gov).

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Skin toxicity predicts efficacy to sorafenib in patients with advanced hepatocellular carcinoma

Abstract: Skin toxicity was associated with favorable outcomes with sorafenib therapy for advanced HCC. Nursing intervention contributed to better adherence, which may improve the efficacy of sorafenib.

Cited by 30 publications

References 36 publications

Longitudinal alterations in health-related quality of life and its impact on the clinical course of patients with advanced hepatocellular carcinoma receiving sorafenib treatment

Longitudinal alterations in health-related quality of life and its impact on the clinical course of patients with advanced hepatocellular carcinoma receiving sorafenib treatment

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

Phase I study of nintedanib in Japanese patients with advanced hepatocellular carcinoma and liver impairment

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