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  Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 54  |  Issue : 3  |  Page : 547-549
 

Short-term efficacy and safety of apatinib in advanced squamous cell carcinoma of the lung


1 Department of Medical Oncology, Xuzhou Central Hospital, Xuzhou 277100, China
2 Department of Neurology, Xuzhou Central Hospital, Xuzhou 277100, China

Date of Web Publication24-May-2018

Correspondence Address:
Dr. Liang Han
Department of Medical Oncology, Xuzhou Central Hospital, Xuzhou 277100
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijc.IJC_379_17

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 » Abstract 


OBJECTIVE: To evaluate the short-term efficacy and safety of apatinib alone or combined with chemotherapy in the treatment of advanced squamous cell lung cancer. METHODS: Forty patients with advanced squamous cell lung carcinoma were enrolled in this study, who were treated in Xuzhou Central Hospital from 2014 to 2015. All patients underwent first-line or more chemotherapy. Patients were administrated with apatinib 425 mg/day, alone or combined with chemotherapy. The short-term efficacy was evaluated according to the RECIST criteria. The main safety event was evaluated by CTC-AE criteria. RESULTS: Among all the 40 patients, partial response in 5 cases, stable disease in 24 cases, progressive disease in 11 cases, overall response rate in 12.5%, disease control rate in 72.5%, the median progression-free survival was 3.7 months. The main adverse events were leukopenia, fatigue, and hypertension. Most of the adverse events were grade I and II level. CONCLUSION: The use of apatinib alone or combined with chemotherapy in patients with advanced or metastatic squamous cell lung carcinoma demonstrates a high response rate, favorable tolerability profile.


Keywords: Apatinib, nonsmall cell lung cancer, squamous cell lung cancer


How to cite this article:
Li X, Le L, Han L, Zhang Y, Sun S. Short-term efficacy and safety of apatinib in advanced squamous cell carcinoma of the lung. Indian J Cancer 2017;54:547-9

How to cite this URL:
Li X, Le L, Han L, Zhang Y, Sun S. Short-term efficacy and safety of apatinib in advanced squamous cell carcinoma of the lung. Indian J Cancer [serial online] 2017 [cited 2019 Aug 23];54:547-9. Available from: http://www.indianjcancer.com/text.asp?2017/54/3/547/233155

Xiaowu Li and Lechao Le contributed equally.





 » Introduction Top


Nonsmall cell lung cancer (NSCLC) is the most common form of lung cancer accounting up to 85% of all case.[1] It can be divided into three different subtypes:[2] adenocarcinoma, squamous cell carcinoma, and large cell carcinoma, with squamous cell carcinoma of the lung comprising approximately 30%. Currently, the NCCN panel recommends traditional cytotoxic chemotherapy as the preferred first- or second-line therapy for patients with recurrent or metastatic squamous cell carcinoma.[3] Despite the fact that chemotherapy can prolong survival time for patients who failed first- or second-line therapy, a considerable proportion of patients cannot tolerate the toxicities of chemotherapy. Apatinib (Jiangsu Hengrui Medicine, China), a small molecule vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor, has been shown to have potential as a therapeutic agent for malignancies. It can effectively block proliferation and tube formation of human umbilical vein endothelial cells and inhibits the growth of xenograft tumors. However, the information concerning apatinib in advanced squamous cell lung cancer is very limited. Thus, we reviewed 40 patients with advanced squamous cell lung cancer who were treated in Xuzhou Central Hospital from 2014 to 2015 to evaluate the short-term efficacy and safety of apatinib alone or combined with chemotherapy.


 » Materials and Methods Top


Patients

We carried out a retrospective study of 40 patients with advanced squamous cell lung carcinoma diagnosed at the Xuzhou Central Hospital from January 2014 to December 2015. Inclusion criteria were (1) histological or cytological diagnosis of squamous or adenosquamous cell lung carcinoma according to histopathological criteria (the World Health Organization, 2004); (2) patients has progressed on or after first-line chemotherapy; (3) one or more measurable target lesions as defined by the Response Evaluation Criteria in Solid Tumors; and (4) Eastern Cooperative Oncology Group (ECOG) performance status of 0–2, and acceptable hematologic, hepatic, and renal function. The study was approved by the Institutional review board of Xuzhou Central Hospital.

Treatment methods

Apatinib (Jiangsu Hengrui Medicine, China) was administered at a dose of 425 mg once daily. One treatment cycle was 28 days long. One dose reduction for drug-related toxicity was allowed. Treatment would continue until progress or intolerable toxicity occured in disease. The choice of chemotherapy regimes depended on patients' previous treatment, duration of response, and disease state.

Responses and toxicity

Tumor responses were assessed every two cycles or were evaluated early when significant signs of progression appeared. Objective tumor responses were assessed according to the Response Evaluation Criteria in Solid Tumors. Objective tumor responses included complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). The disease control rate (DCR) was defined as the addition of objective response and stabilization rates (CR + PR + SD). Treatment-related toxicities were assessed according to the National Cancer Institute Common Toxicity Criteria version 4.0 (CTC4.0).

Follow-up

The median time of follow-up was 12.3 months (range 1–36 months). All the patients who were evaluated for tumor response had progression-free survival (PFS) and overall survival (OS). PFS was calculated from the first day of apatinib to documented progression or death from any cause. OS was considered as the time from the first day of apatinib treatment to death or last follow-up.


 » Results Top


Patient characteristics

Patients' characteristics are presented in [Table 1]. Nearly 40 patients had a median age of 65 years (range: 46–84 years), comprising 26 males and 14 females (male/female [M/F] ratio = 1.8). Of these, there were 18 cases that were at stage III B and 22 cases at stage IV. Eighteen patients received apatinib as second-line therapy and 22 as further-line treatment. Thirty-three patients had performance status (PS) of 0-1 and 17 had PS of 2. No one has history of bleeding before receiving therapy of apatinib.
Table 1: Baseline characteristics of patients

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Short-term efficacy

For all 40 patients, after one treatment cycle, the overall response rate (ORR) and disease control rate (DCR) were 12.5% and 72.5%, respectively. Complete remission (CR) was achieved in 0%, partial remission (PR) in 12.5%, stable disease (SD) in 60%, and progressive disease (PD) in 27.5%. Before the deadline of follow-up, all patients experienced tumor progression, with median time of follow-up of 3.7 months (range: 3.0–4.5 months) [Figure 1].
Figure 1: Progression-free survival curves for the entire population of 40 patients

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Toxicity evaluation

A total of 40 patients were administered at least one cycle of apatinib with or without chemotherapy before the deadline. The most common toxicities were hypertension, proteinuria, and hand-foot syndrome, followed by hematologic toxicity. In addition, among those benefited from the treatment of apatinib, 7 patients presented with central cavitary necrosis of tumor. For most patients, the toxicities were tolerated, which was well relieved by symptomatic treatment without dose adjustment. Five patients required dose modifications because developed grade 3 toxicities, but none showed grade 4 toxicities [Table 2].
Table 2: Adverse eve

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 » Discussion Top


Lung cancer is the leading cause of cancer-related mortality in China. The latest statistical data [4] showed that an estimated 705,000 new cases will be diagnosed and 569,000 deaths are estimated to occur in 2017. As their clinical course is often insidious, lacks specific clinical presentation, >70% of lung cancer were usually in advanced stage when diagnosed. In recent years, much progress has been made for lung adenocarcinoma such as screening, minimally invasive techniques for diagnosis and treatment in chemotherapy, radiation, targeted therapies, and immunotherapies.[5],[6] As most patients with squamous cell lung cancer do not have a genetic driver mutation, platinum-based doublet chemotherapy is still the standard treatment option for them.[7],[8] However, most patients experience disease progression within 6 months from first-line therapy and require salvage therapy. Docetaxel are considered standard second-line therapies based on several randomized controlled trials. Despite the fact that a considerable proportion of patients (26%–38%) are suitable for post second-line therapies, the quality and quantity of the available drugs in this setting are poor.

As we know, angiogenesis is a key process for cell growth, especially for tumor growth.[9] Moreover, the vascular epidermal growth factor (VEGF) can activate the downstream pathway to stimulate the proliferation of vessel endothelium through binding VEGFR, thus leading to the growth of tumor.[10] Studies [11] have revealed that antiangiogenesis drugs inhibit the growth of solid tumors.

Apatinib, a small-molecule VEGFR-2 tyrosine kinase inhibitor, has been proved to improve PFS and OS in patients with metastatic gastric cancer.[12],[13],[14] Several clinical experiments [15],[16],[17],[18] indicated that apatinib has potential as a therapeutic agent for NSCLC. Thus, conducted this retrospective analysis to investigate the efficacy of apatinib in squamous cell lung cancer as salvage treatment. In our study, the DCR and ORR were 72.5 and 12.5%, and the median PFS was 3.7 months. Our results indicate that apatinib seems to have superior efficacy as salvage therapy in squamous cell lung cancer.

The most common toxicities were hypertension, proteinuria, and hand-foot syndrome, which is in agreement with the previous study.[16],[18] Bevacizumab is the first generation of antiangiogenesis drug. Because of the serious toxicities of hemorrhage, it is not approved for the treatment of squamous cell carcinoma. Of note, no hemorrhage occurred in the present study, suggesting safety of this novel small-molecule oral agent. Thus, apatinib may be a promising drug to change the guideline that antiangiogenesis drug is not recommended for patients with squamous cell lung carcinoma. To answer these questions, conducting more clinical trials is ideal. In addition, among those benefited from the treatment of apatinib, many presented with central cavitary necrosis of tumor, which is consistent with the antitumor mechanism of apatinib.


 » Conclusion Top


The present results suggest that apatinib may be a promising therapeutic drug for patients with advanced squamous cell lung cancer. As for the future, whether apatinib can break the deadlock that antiangiogenesis drug is not supposed to be used in squamous cell lung carcinoma needs to be seen? Conducting more large-scale, prospective randomized clinical studies are needed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 » References Top

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Goldstraw P, Crowley J, Chansky K, Giroux DJ, Groome PA, Rami-Porta R, et al. The IASLC Lung Cancer Staging Project: Proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours. J Thorac Oncol 2007;2:706-14.  Back to cited text no. 2
    
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Ettinger DS, Wood DE, Akerley W, Bazhenova LA, Borghaei H, Camidge DR, et al. NCCN guidelines insights: Non-small cell lung cancer, version 4.2016. J Natl Compr Canc Netw 2016;14:255-64.  Back to cited text no. 3
    
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Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, et al. Cancer statistics in China, 2015. CA Cancer J Clin 2016;66:115-32.  Back to cited text no. 4
    
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Ellis PM, Coakley N, Feld R, Kuruvilla S, Ung YC. Use of the epidermal growth factor receptor inhibitors gefitinib, erlotinib, afatinib, dacomitinib, and icotinib in the treatment of non-small-cell lung cancer: A systematic review. Curr Oncol 2015;22:e183-215.  Back to cited text no. 5
    
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Riely GJ, Yu HA. EGFR: The paradigm of an oncogene-driven lung cancer. Clin Cancer Res 2015;21:2221-6.  Back to cited text no. 6
    
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Xing P, Wang S, Hao X, Zhang T, Li J. Clinical data from the real world: Efficacy of Crizotinib in Chinese patients with advanced ALK-rearranged non-small cell lung cancer and brain metastases. Oncotarget 2016;7:84666-74.  Back to cited text no. 7
    
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Gainor JF, Tan DS, De Pas T, Solomon BJ, Ahmad A, Lazzari C, et al. Progression-free and overall survival in ALK-positive NSCLC patients treated with sequential crizotinib and ceritinib. Clin Cancer Res 2015;21:2745-52.  Back to cited text no. 8
    
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Weis SM, Cheresh DA. Tumor angiogenesis: Molecular pathways and therapeutic targets. Nat Med 2011;17:1359-70.  Back to cited text no. 9
    
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Ferrara N, Adamis AP. Ten years of anti-vascular endothelial growth factor therapy. Nat Rev Drug Discov 2016;15:385-403.  Back to cited text no. 10
    
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Abhinand CS, Raju R, Soumya SJ, Arya PS, Sudhakaran PR. VEGF-A/VEGFR2 signaling network in endothelial cells relevant to angiogenesis. J Cell Commun Signal 2016;10:347-54.  Back to cited text no. 11
    
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Roviello G, Ravelli A, Polom K, Petrioli R, Marano L, Marrelli D, et al. Apatinib: A novel receptor tyrosine kinase inhibitor for the treatment of gastric cancer. Cancer Lett 2016;372:187-91.  Back to cited text no. 12
    
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Lin C, Wang S, Xie W, Zheng R, Gan Y, Chang J. Apatinib inhibits cellular invasion and migration by fusion kinase KIF5B-RET via suppressing RET/Src signaling pathway. Oncotarget 2016;7:59236-44.  Back to cited text no. 13
    
14.
Li J, Qin S, Xu J, Xiong J, Wu C, Bai Y, et al. Randomized, double-blind, placebo-controlled phase III trial of apatinib in patients with chemotherapy-refractory advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction. J Clin Oncol 2016;34:1448-54.  Back to cited text no. 14
    
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Scott AJ, Messersmith WA, Jimeno A. Apatinib: A promising oral antiangiogenic agent in the treatment of multiple solid tumors. Drugs Today (Barc) 2015;51:223-9.  Back to cited text no. 15
    
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Peng H, Zhang Q, Li J, Zhang N, Hua Y, Xu L, et al. Apatinib inhibits VEGF signaling and promotes apoptosis in intrahepatic cholangiocarcinoma. Oncotarget 2016;7:17220-9.  Back to cited text no. 16
    
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Hu X, Cao J, Hu W, Wu C, Pan Y, Cai L, et al. Multicenter phase II study of apatinib in non-triple-negative metastatic breast cancer. BMC Cancer 2014;14:820.  Back to cited text no. 17
    
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Ji G, Hong L, Yang P. Successful treatment of advanced malignant fibrous histiocytoma of the right forearm with apatinib: A case report. Onco Targets Ther 2016;9:643-7.  Back to cited text no. 18
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2]



 

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