Hand-Foot Syndrome and Post-Progression Treatment Are the Good Predictors of Better Survival in Advanced Hepatocellular Carcinoma Treated with Sorafenib: A Multicenter Study

Ogawa, Chikara; Morita, Masahiro; Omura, Akina; Noda, Teruyo; Kubo, Atsushi; Matsunaka, Toshihiro; Tamaki, Hiroyuki; Shibatoge, Mitsushige; Tsutsui, Akemi; Senoh, Tomonori; Nagano, Takuya; Takaguchi, Kouichi; Tani, Joji; Morishita, Asahiro; Yoneyama, Hirohito; Masaki, Tsutomu; Moriya, Akio; Ando, Masaharu; Deguchi, Akihiro; Kokudo, Yasutaka; Minami, Yasunori; Ueshima, Kazuomi; Sakurai, Toshiharu; Nishida, Naoshi; Kudo, Masatoshi

doi:10.1159/000481241

Cited by 24 publications

(19 citation statements)

References 27 publications

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“…Thus, HFSR should be kept in mind as a commonly occurring AE in patients with a history of that condition during previous SOR and/or REG treatments. HFSR in association with SOR has been reported as a factor predicting a better therapeutic effect of SOR for HCC . Based on these findings, the relationship between HFSR and therapeutic response with LEN treatment should be analyzed in the future.…”

Section: Discussionmentioning

confidence: 95%

Clinical features of lenvatinib for unresectable hepatocellular carcinoma in real‐world conditions: Multicenter analysis

et al. 2018

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Background/AimPresently, there are no therapeutic options for unresectable hepatocellular carcinoma (u‐HCC) patients who are intolerant to sorafenib or regorafenib failure. There have been no reports with detailed clinical findings of lenvatinib (LEN), a newly developed first‐line tyrosine kinase inhibitor (TKI), obtained in real‐world practice. We aimed to elucidate the therapeutic efficacy of LEN.Materials/MethodsFrom March to August 2018, 105 u‐HCC patients were treated with LEN. Following exclusion of those who started with a reduced LEN dose and/or had a short observation period (<2 weeks), 77 patients (72.0 ± 8.9 years, 59 males, 8 mg/12 mg = 49/28, Liver Cancer Study Group of Japan 6th [LCSGJ]‐TNM stage II/III/IVa/IVb = 8/28/4/37, and American Joint Committee on Cancer/Union for International Cancer Control 8th [AJCC/UICC]‐TNM stage IB:II:IIIA:IIIB:IVA:IVB = 2:27:6:5:9:28) were divided into two groups (TKI naïve [n = 33] and TKI experienced [n = 44], including 11 with regorafenib history). Therapeutic response was evaluated using mRECIST. Clinical data were retrospectively evaluated.ResultsThere were significant differences in age (74.6 ± 11.2 vs 70.0 ± 5.9 years, P = 0.040), LCSGJ‐TNM (II:III:IVa:IVb = 8:12:1:12 vs 0:16:3:25, P = 0.006), and AJCC/UICC‐TNM (IB:II:IIIA:IIIB:IVA:IVB = 2:17:1:1:4:8 vs 0:10:5:4:5:20, P = 0.028), while hepatic reserve function, adverse event (AE) profiles, and progression‐free survival (89.7%/80.4% vs 90.5%/80.1%, P = 0.499) and overall survival (96.7%/96.7% vs 100%/92.3%, P = 0.769) after 4 and 12 weeks were not significantly different between the TKI‐naïve and TKI‐experienced groups. Overall response rate and disease control rate at 4 weeks (n = 52) were 38.5% and 80.8%, respectively, and 32.4% and 70.3%, respectively, at 12 weeks (n = 37). A significant decline in log10 AFP from the baseline to 4 weeks after introducing LEN was observed in patients with PR and SD (2.047 ± 1.148 vs 1.796 ± 1.179, P < 0.001).ConclusionRegardless of past TKI therapy, therapeutic response and AEs after introducing LEN were similar. LEN may be an important treatment for the present unmet need regarding TKI treatment against u‐HCC.

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Section: Discussionmentioning

confidence: 95%

Clinical features of lenvatinib for unresectable hepatocellular carcinoma in real‐world conditions: Multicenter analysis

et al. 2018

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“…HFSR is thought to be a predictor of good therapeutic response in patients receiving LEN treatment as well as those treated with SOR. 30 On the other hand, appetite loss can cause stoppage of LEN and the BMI of patients with that AE was significantly lower (P < 0.001). Porta et al reported that a low dose and treatment discontinuations were correlated with worse survival in renal cell carcinoma patients treated with sunitinib, indicating the importance of maintaining dose intensity.…”

Section: Discussionmentioning

confidence: 96%

“…The frequency of each AE (all grades) in all patients was similar to that of patients with good hepatic function (mALBI 1, 2a), except for HFSR. HFSR is thought to be a predictor of good therapeutic response in patients receiving LEN treatment as well as those treated with SOR . On the other hand, appetite loss can cause stoppage of LEN and the BMI of patients with that AE was significantly lower ( P < 0.001).…”

Section: Discussionmentioning

confidence: 99%

Prognostic factor of lenvatinib for unresectable hepatocellular carcinoma in real‐world conditions—Multicenter analysis

et al. 2019

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Background/aim We assessed suitable factors indicating newly developed lenvatinib (LEN) treatment for unresectable hepatocellular carcinoma (u‐HCC) by investigating real‐world clinical features of patients. Materials/methods One hundred fifty two u‐HCC patients, who receive LEN treatment from March to December 2018, were enrolled. (Child‐Pugh score [CPS] 5/6/7/8 = 76/61/13/2, modified albumin‐bilirubin grade [mALBI] 1/2a/2b/3 = 53/35/60/4). Clinical features were evaluated retrospectively. Results Overall‐response rate (ORR)/disease control rate (DCR) at 1 month after starting LEN were 38.7%/86.0%, respectively. Estimated median time to progression (TTP) was 7.0 months, while median survival time was not reached within the observation period. CPS (≥7) and past history of tyrosine‐kinase inhibitor (TKI) were not significant prognostic factors. mALBI ≥2b was an only significant prognostic factor (HR 4.632, 95%CI 1.649‐13.02, P = 0.004) in Cox‐hazard multivariate analysis. In patients with Child‐Pugh A, c‐index/Akaike's information criterion (AIC) of prognostic predictive value of mALBI were superior to CPS (0.682/135.6 vs 0.652/138.7), while those of stopping LEN also showed that mALBI was better (0.575/447.3 vs 0.562/447.8). Additional analysis of patients with good mALBI (1/2a) revealed that time to stopping LEN was significantly shorter in those with the adverse event (AE) of appetite loss (any grade) than those without ( P = 0.006) and body mass index (BMI) was also lower in patients with that AE (20.3 ± 3.0 vs 23.6 ± 4.0kg/m 2 , P < 0.001), while patients with a hand‐foot skin reaction (any grade) showed good ORR/DCR (59.1%/86.4%) and longer TTP as compared to patients without ( P = 0.007). Conclusion Good hepatic function (mALBI 1/2a) is the best indication for LEN, while potential appetite loss in association with low BMI should be kept in mind in such cases.

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“…Some adverse effects such as HFS are associated with better survival; however, in more vulnerable patients, they can also lead to a greater impact on quality of life [24, 25]. In a meta-analysis of 14 clinical trials, patients taking capecitabine who developed HFS had a longer overall survival than patients who did not develop HFS: 1100 days (95% confidence interval 1007–1200) vs. 691 days, with a hazard ratio of 0.61 (95% confidence interval 0.56–0.66) [24].…”

Section: Discussionmentioning

confidence: 99%

Real-World Adverse Effects of Capecitabine Toxicity in an Elderly Population

Beek¹,

Roukens²,

Jacobs³

et al. 2018

Drugs - Real World Outcomes

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BackgroundFew studies have assessed the safety and effectiveness of the numerous available chemotherapeutic therapies for geriatric oncology patients. Most safety studies are conducted in large trials, and there is some uncertainty surrounding whether the results would be the same in typical daily use.ObjectiveThis retrospective study aims to assess the adverse effects of real-world capecitabine use in elderly patients.MethodsWe reviewed the records of patients treated with capecitabine in an oncology department of a University Clinic in Nijmegen, The Netherlands. We scored adverse effects such as hand-foot syndrome and diarrhea, and dosage adjustments and the reasons for them. In total, 132 patients were included, 69 of whom were aged 70 years or below (mean age: 57 years), while 63 were aged older than 70 years (mean age: 74 years).ResultsPatients aged over 70 years experienced more serious adverse effects than younger patients. Grade 2 or 3 hand-foot syndrome toxicity was experienced by 20.2% of patients aged younger than 70 years and by 34.9% of patients older than 70 years (p = 0.059). Grade 2, 3, or 4 diarrhea was experienced by 17.4% of the patients aged younger than 70 years but by 31.7% of the patients aged older than 70 years (p = 0.044). Dosage was adjusted for 27/69 patients in the younger group and 52/63 patients in the older group (p = 0.001).ConclusionThe difference in observed adverse effects cannot be the sole explanation for the high incidence of observed dose adjustments. A prospective follow-up study of elderly patients using capecitabine outside clinical trials is needed to evaluate the optimum balance between adverse effects and efficacy.

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Hand-Foot Syndrome and Post-Progression Treatment Are the Good Predictors of Better Survival in Advanced Hepatocellular Carcinoma Treated with Sorafenib: A Multicenter Study

Cited by 24 publications

References 27 publications

Clinical features of lenvatinib for unresectable hepatocellular carcinoma in real‐world conditions: Multicenter analysis

Clinical features of lenvatinib for unresectable hepatocellular carcinoma in real‐world conditions: Multicenter analysis

Prognostic factor of lenvatinib for unresectable hepatocellular carcinoma in real‐world conditions—Multicenter analysis

Real-World Adverse Effects of Capecitabine Toxicity in an Elderly Population

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