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Predictors of Apatinib in the Treatment of Advanced Primary Liver Cancer

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Predictors of Apatinib in the Treatment of Advanced Primary Liver Cancer Research Article Clinics in Oncology Published: 26 May, 2020 Predictors of Apatinib in the Treatment of Advanced Primary Liver Cancer Ren-Wang Chen1, Chi-Dan Wan2, Tao Zhang1, Liang-Liang Shi1, Guo-Run Fan3, Jian Chang1, Jing Zhan4, Xiao-Xiao He4, Meng-Jun Qiu4, Sheng-Li Yang1* and Jian-Li Hu1* 1Department of Cancer, Huazhong University of Science and Technology, China 2Department of Hepatobiliary Surgery, Huazhong University of Science and Technology, China 3Department of Otorhinolaryngology, Huazhong University of Science and Technology, China 4Department of Gastroenterology, Huazhong University of Science and Technology, China Abstract Objective: The purpose of this study is to investigate the efficacy of Apatinib in the treatment of advanced Primary Liver Cancer (PLC), analyze the factors that influence the efficacy, and find out the biomarkers that effectively predict the efficacy. Methods: Data from 87 patients with advanced PLC who received Apatinib as first-line treatment at two medical centers were retrospectively analyzed. We analyzed the clinical features and explore the prognostic factors of PLC. We correlated the clinical markers with the efficacy of Apatinib. Results: The Progression Free Survival (PFS) of the 87 patients was 8.6 ± 1.9 months (95% CI: 5.0 to 12.3). 3-month, 4-month and 5-month disease control rates were 69.0%, 59.2% and 53.5% OPEN ACCESS respectively. Univariate analysis indicated that Alpha-Feto Protein (AFP), Alkaline Phosphatase (ALP), Lactate Dehydrogenase (LDH) and cirrhosis were associated with prognosis (P<0.05). *Correspondence: Multivariate analysis indicated that ALP was negatively associated with prognosis (P<0.05). Chi- Jian-Li Hu, Department of Cancer, square test indicated that the serum AFP and LDH level as well as tumor diameter were statistically Huazhong University of Science different between PFS ≤ 3-month and PFS>3-month groups (P<0.05). The survival analysis was and Technology, Tongji Medical conducted that the blood levels of AFP, ALP and LDH as well as with or without cirrhosis before College, Wuhan 430022, China, Tel: starting Apatinib treatment can influence the survival rate of patients. 8613871268129; Conclusion: Apatinib is an effective treatment for advanced PLC. Serum AFP, ALP and LDH level, E-mail: [email protected] as well as whether there is cirrhosis can be used to predict the efficacy of Apatinib. Sheng-Li Yang, Department of Cancer, Huazhong University of Science Keywords: Apatinib; Primary liver cancer; First-line treatment; Efficacy prediction; Prognostic and Technology, Tongji Medical factors College, Wuhan 430022, China, Tel: 8615994284798; Introduction E-mail: [email protected] Primary Liver Cancer (PLC) is one of the most common clinical malignant tumors. More than Received Date: 28 Apr 2020 1.5 million people worldwide are first diagnosed with PLC each year [1,2]. According to data from Accepted Date: 22 May 2020 the Chinese tumor registration in 2015, both the incidence and mortality rates of liver cancer in Published Date: 26 May 2020 China ranked No.1 in the world, accounting for about 55% of the cases of liver cancer and 50% of Citation: the cases of deaths in the world [3,4]. Surgery is still the first choice of treatment for PLC. Other Chen R-W, Wan C-D, Zhang T, Shi L-L, treatments, such as cutaneous hepatic arterial chemotherapy (TACE), Radio Frequency Ablation Fan G-R, Chang J, et al. Predictors of (RFA) and traditional Chinese medicine treatments can improve the survival rate of patients and Apatinib in the Treatment of Advanced life-improvement therapy can also help to some extent [5,6]. Nevertheless, the long-term outcome Primary Liver Cancer. Clin Oncol. 2020; of PLC still cannot be improved. 5: 1704. Sorafenib is an effective treatment method for advanced PLC patients [7,8], although its limited Copyright © 2020 Sheng-Li Yang and efficacy, its high cost and the inability to select effective cohort from large number of patients has Jian-Li Hu. This is an open access limited its clinical usage. With the development of anti-angiogenesis drugs, anti-tumor drugs article distributed under the Creative acting on the signaling pathway of Vascular Endothelial Growth Factor (VEGF) and its receptor Commons Attribution License, which have attracted more attention [9-12]. Among them, Apatinib is a new oral anti-angiogenesis permits unrestricted use, distribution, small-molecule, which can highly selectively bind and inhibit Vascular Endothelial Cell Growth and reproduction in any medium, Factor Receptor-2 (VEGFR-2), thereby inhibiting tumor angiogenesis and tumor growth [13]. It is currently approved for the treatment of advanced gastric cancer [14]. Nonetheless, clinical studies provided the original work is properly have been carried out to use Apatinib as a treatment for a variety of solid tumors [15-17]. cited. Remedy Publications LLC., | http://clinicsinoncology.com/ 1 2020 | Volume 5 | Article 1704 Sheng-Li Yang and Jian-Li Hu, et al., Clinics in Oncology - General Oncology This study analyzes the progress-free survival time, levels of clinical biochemical markers and tumor tissue molecular phenotype in advanced PLC patients who received Apatinib as first-line treatment. We also determined the possible factors which can influence the prognosis. Patients who responded well to the Apatinib treatment were selected from a large number of advanced PLC patients, in an attempt to explore a new and suitable first-line treatment, which can benefit the majority of patients with advanced PLC. Materials and Methods Clinical data collection We collected 87 cases of patients diagnosed with PLC via clinical or pathological diagnosis in the affiliated Union hospital and Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology from February 2015 to December 2017. All patients took Apatinib as the only first-line treatment option. The therapeutic Figure 1: Dynamic liver computed tomography scan revealed the change dose for each patient was 250 mg orally daily until intolerance or of liver tumors before (A and C) and after (B and D) treatment. The image disease progression. We performed a retrospect review of the cases B revealed marked reduces of the tumor. The image D revealed slightly enlarged of the tumor and notable necrosis in the center. and analyzed the patients’ clinical biochemical characteristics. Eligibility criteria included Eastern Cooperative Oncology Group Table 1: Main demographic, biochemical, and clinical characteristics of the 87 (ECOG) performance status of 0 to 2 and normal initial laboratory PLC patients. tests. Those who disagreed and were under 18 years of age have been Variable Unit Value excluded. Age years 50.4 (27-76) Observation indices Gender male 82 (94.3%) Observed clinical indices include age (≤ 50 y/>50 y), gender, Albumin g/L 36 (24-50) cirrhosis, tumor size (≤ 5 cm/>5 cm); blood biochemical indices: ALT U/L 71 (2-1478) Alpha-Feto Protein AFP (≤ 200 μg/L/>200 μg/L), Cancer Embryo Antigen CEA (≤ 5 μg/L/>5 μg/L), albumin(≤ 35g/L/>35g/L), Alkaline AST U/L 79 (11-1021) Phosphatase ALP (≤ 140 U/L/>140U/L), Lactate Dehydrogenase ALP U/L 63 (16-159) LDH (≤ 220 U/L/>22 0U/L), Hemoglobin HB (≤ 120 G/L/>120 G/L), LDH U/L 313 (32-2227) Alamine Aminotransferase ALT (≤ 40 U/L/>40 U/L), Aspartate CEA μg/L 3.7 (1-41) Aminotransferase AST (≤ 40 U/L/>40 U/L). Tumor size cm 5.6 (1.5-20) Follow-up results AFP μg/L 7071 (2-80000) All 87 of patients with PLC were followed up. The average follow- HB g/L 123.6 (70-158) up duration was 12.6 months (range 1 to 33 months). 45 of the 87 cases progressed. CT or MRI images were obtained at least every 3 Data are presented as median (range) or absolute frequency (%). PLC: Primary Liver Cancer; ALT: Alanine Aminotransferase; AST: Aspartate months during the postoperative follow-up. Tumor recurrence was Aminotransferase; ALP: Alkaline Phosphatase; LDH: Lactate Dehydrogenase; diagnosed by contrast-enhanced CT or MRI. Information on deaths CEA: Carcinoembryonic Antigen; AFP: Alpha-Fetoprotein; HB: Hemoglobin was obtained from the social security death index, medical records or showed xanthochromia. 19 cases did not show any obvious clinical notifications from family members. The primary endpoint was death symptoms and were diagnosed with hepatoncus during physical or tumor progress. examination (Figure 1). 76 cases had a history of hepatitis B, and 3 Statistical treatment cases had a history of hepatitis C. 48 cases had liver cirrhosis (55.2%). 46 cases (52.9%) had increased levels of serum AFP (>200 μg/L), The data were analyzed using SPSS 25.0 statistical software. while 41 cases (37.1%) had levels ≤ 200 μg/L. 21 cases (24.1%) had Chi-square tests were used to compare the age, cirrhosis, albumin, increased serum ALP levels (>140U/L), while 67 (75.9%) had levels ≤ AFP, HB, CEA, ALP, LDH and tumor size between PFS ≤ 3 month 140 U/L. 51 cases (58.6%) had increased serum ALT levels (>40 U/L), and PFS>3 month groups. Kaplan-Meier survival curve was used to while 36 (41.4%) had levels ≤ 40 U/L. 50 cases (57.5%) had increased analyze the differences in the effects of various clinical biochemical serum AST levels (>40 U/L), while 37 (42.5%) had levels ≤ 40 U/L.24 indices on prognosis, univariate prognostic analysis was performed cases (27.6%) had increased serum LDH levels (>220 U/L), while 17 using Log-rank method, and COX regression was performed for (19.5%) had levels ≤ 220 U/L and no data for remaining cases. 14 multivariate analysis. α=0.05 was the inspection level and P<0.05 was cases (16.1%) had elevated serum levels of CEA (>5 μg/L), and 73 considered to be statistical different.
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