Increased cumulative doses and appearance of hand‐foot skin reaction prolonged progression free survival in sorafenib‐treated advanced hepatocellular carcinoma patients

Abstract

Sorafenib has been recommended as a new palliative therapy for advanced hepatocellular carcinoma (HCC). However, the clinical outcome of patients receiving sorafenib therapy varies. This study sought to identify which clinical method could be used to predict clinical outcome of sorafenib monotherapy in patients with advanced HCC. A total of 146 advanced HCC patients with Child-Pugh A liver function were enrolled from June 2011 to September 2015. Sorafenib doses ranged from 200 mg once daily to 400 mg twice daily. Clinical and pathological parameters were collected. There was no predefined primary endpoint. Tumor response rate, adverse events, overall survival (OS), and progression-free survival (PFS) were analyzed. The follow-up period was 1718 days (median: 859 days). The median dosage of sorafenib was 562.35 mg.Forty patients (27.4%) had stable disease and 106 patients (72.6%) had progression disease. The OS was 432.21 ± 360.52 days (median: 329 days) and PFS was 167.05 ± 166.50 days (median: 102.5 days). No sorafenib toxic effect-related mortality was encountered. The most common severe adverse events (≧grade 3) were hand-foot skin reactions (HFSR) (16, 11.0%), diarrhea (7, 4.8%), and alopecia (1, 0.7%). The following patients had longer median PFS (mPFS): those receiving total dosage > 55000 mg (217 vs.63 days; HR = 0.20,95%CI = 0.11-0.38; p < 0.001), those receiving daily dosage <562 mg (140 vs.69 days; HR = 0.27, 95%CI = 0.17-0.46; p < 0.001), those with treatment durations > 112 days (231vs.64 days; HR = 0.37, 95%CI = 0.19-0.74; p < 0.001), and those with HFSR (105 vs.75 days; HR = 0.60,95% CI = 0.6-0.98; p = 0.04). In conclusion, increased cumulative doses of sorafenib as well as the appearance of HFSR were indicators of prolonged mPFS in sorafenib-treated advanced HCC patients.

Treatment of Hepatocellular Carcinoma-associated Portal Vein Tumor Thrombus Using Combination of Portal Vein Stent Insertion and Endovascular Lodine-125 Seed-strip Implantation Followed by Transcatheter Arterial Chemoembolization- Sorafenib

“…And the liver function can be aggravated by repeated TACE and long-term sorafenib, as described above. This, in turn, requires modi cations to or discontinuations of TACE-S treatment regimens, thus potentially constraining their therapeutic value [36,37]. Patients with PVTT also often died of acute variceal bleeding rather than due to direct damage from the liver tumor itself [32].…”

Effect of UDP‐glucuronosyltransferase 1A1 activity on risk for developing Gilbert's syndrome

“…However, as more SNPs in the UGT1A1 gene were found, we determined that our method of classifying study subjects was inaccurate. For example, UGT1A1 activities may differ considerably among subjects who carry compound heterozygous variations because some carry two while others can carry three or four SNPs …”

“…Since 2000, we have published 14 studies on the relationship between variants in the UGT1A1 gene and Gilbert's syndrome (or neonatal hyperbilirubinemia). 9,11,[17][18][19][20][21][22][23][24][25][26][27][28] In our previous reports, the study subjects were usually divided into several groups, such as those carrying the wild type UGT1A1 gene, those carrying heterozygous variations, subjects with compound heterozygous variations, and those carrying homozygous and compound homozygous variations in the UGT1A1 gene, because we assumed that UGT1A1 activity gradually decreased as the number of variant alleles increased. However, as more SNPs in the UGT1A1 gene were found, we determined that our method of classifying study subjects was inaccurate.…”

“…For example, UGT1A1 activities may differ considerably among subjects who carry compound heterozygous variations because some carry two while others can carry three or four SNPs. 9,11,[17][18][19][20][21][22][23][24][25][26][27][28] Classifying subjects based on genotype is a more suitable method because genotypes represent variation of all SNPs in the UGT1A1 gene. 11 However, in this study, we realized that we would encounter it would be a laborious process to precisely analyze the OR for each genotype since the number (n = 24) of genotypes is too much.…”

Evolving Treatment of Advanced Hepatocellular Carcinoma in the Asia–Pacific Region: A Review and Multidisciplinary Expert Opinion

“…Although no significant difference in OS benefit has been shown between sorafenib and lenvatinib, in trials or in real-world clinical practice [ 41 ], lenvatinib may be preferred for antitumour efficacy, as defined by response rates and PFS, and for tolerability (hypertension with lenvatinib versus hand–foot skin reaction with sorafenib). Although the occurrence of hand–foot skin reaction appears to be associated with better survival [ 42 , 43 ], the quality of life of patients experiencing this AE may be significantly impaired; physicians observe that hand–foot skin reaction can be a barrier to the acceptance of sorafenib by some patients. The notoriety of this AE reflects the longevity of use of sorafenib and the communication, throughout its period of use, of anecdotal information among patients and physicians.…”