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CORRESPONDENCE
Year : 2019  |  Volume : 15  |  Issue : 2  |  Page : 442-446

Apatinib and S-1 combination therapy for the treatment of advanced head and neck neoplasms: Three case reports


Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong Province, China

Date of Web Publication1-Apr-2019

Correspondence Address:
Dr. Xin Ye
Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jingwuweiqi Road, Jinan, Shandong Province 250021
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.JCRT_894_18

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 > Abstract 


Apatinib, one of the novel oral antiangiogenic agents, shows survival benefits in treating advanced or metastatic gastric adenocarcinoma. However, its efficacy in treating advanced head and neck neoplasms has not been reported. Herein, three elderly men with advanced head and neck neoplasms were treated with apatinib and S-1. Their initial diagnoses were hypopharyngeal carcinoma, metastatic squamous cell carcinoma of head and neck, and squamous cell carcinoma of the pyriform sinus. All patients underwent repeated chemotherapy but developed disease progression. As they refused radiotherapy due to its serious adverse reaction, apatinib was administered at a dose of 425 mg daily and S-1 at 60 mg twice daily. Thirty days after apatinib administration, the patients achieved partial response according to the Response Evaluation Criteria in Solid Tumors 1.1 standard. Mild toxicity or drug-related side effect was observed during the treatment. Therefore, apatinib and S-1 could be the new treatment option for advanced head and neck neoplasms. However, clinical trials are required to confirm their efficacy and safety.

Keywords: Angiogenesis inhibitor, apatinib, case report, hypopharyngeal carcinoma, S-1


How to cite this article:
Meng M, Ye X, Yang X, Huang G, Wei Z, Ni Y, Li W, Han X, Wang J. Apatinib and S-1 combination therapy for the treatment of advanced head and neck neoplasms: Three case reports. J Can Res Ther 2019;15:442-6

How to cite this URL:
Meng M, Ye X, Yang X, Huang G, Wei Z, Ni Y, Li W, Han X, Wang J. Apatinib and S-1 combination therapy for the treatment of advanced head and neck neoplasms: Three case reports. J Can Res Ther [serial online] 2019 [cited 2019 May 21];15:442-6. Available from: http://www.cancerjournal.net/text.asp?2019/15/2/442/255109




 > Introduction Top


Head and neck cancer is one of the most common cancers, accounting for approximately one-sixth of cancers worldwide.[1] Majority of head and neck cancers (>90%) are squamous cell carcinoma.[2] Currently, they are mainly treated with surgery and chemotherapy. Most patients in stages I and II are mainly treated with surgery or radiotherapy (RT).[3] However, the systematic chemotherapy remains the only effective treatment for patients with recurrence or metastasis, using platinum combined with fluorouracil or taxane (with the promised rate of approximately 30%, progression-free survival of 3–4 months, and overall survival of 6–8 months).[4],[5],[6] Thus, developing novel therapeutic strategies for patients with advanced head and neck cancer is highly necessary.

Apatinib is one of the novel orally smallmolecule tyrosine kinase inhibitors that highly selectively binds to and strongly inhibits vascular endothelial growth factor receptor 2 (VEGFR2), resulting in decreased vascular endothelial growth factor (VEGF) mediated endothelial cell migration, proliferation, and tumor microvascular density. Due to its encouraging results in preclinical and clinical settings,[7],[8],[9] apatinib was approved and launched in the People's Republic of China in 2014 as a subsequentline treatment for patients with advanced gastric cancer. In addition, apatinib has potential antitumor activity in a wide range of advanced solid tumors including non-small cell lung cancer, breast cancer, and hepatocellular carcinoma.[10],[11],[12],[13] They are currently undergoing Phase II/III clinical trials in China. However, the efficacy of apatinib in treating patients with advanced head and neck carcinoma has not been reported. Herein, we report for the first time three patients with advanced head and neck neoplasms who responded to apatinib and S-1.


 > Case Report Top


Patient one, a 66 year-old man, visited the hospital with chief complaints of local mass in the left neck on February 2018. The patient underwent puncture biopsy. Pathological diagnosis confirmed hypopharyngeal carcinoma [Figure 1]. Four-cycle chemotherapy with TP regimen (docetaxel and nedaplatin) was administered.
Figure 1: The patient was diagnosed with hypopharyngeal carcinoma (H and E, ×400)

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In May 2018, neck and chest computed tomography (CT) was performed, revealing increased cervical lymph node metastasis with no significant changes in the neck mass. He refused to receive further cetuximab and vein chemotherapy due to chemotherapeutic toxicities, including nausea, vomiting, and leukopenia.

Most cells showed strong positive staining for VEGFR-2 [Figure 2]. Therefore, the treatment was changed to apatinib and S-1. Apatinib was administered at 425 mg daily and S-1 at 60 mg twice daily. Half a month later, the neck tumor was partially detached, and the lesions significantly shrunk.
Figure 2: Expressions of VEGFR-2 in a tumor section in patient 1 strong positive staining for VEGFR-2 was found in cancer cells (immunohistochemical staining, 400× magnification). VEGFR-2 = Vascular endothelial growth factor receptor 2

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The patient refused to undergo CT every month following apatinib administration. During the 1-month follow-up, the measurable lesion in the neck shrunk [Figure 3]a and [Figure 3]b and continuously shrunk at the 3-month follow-up [Figure 3]c. However, at the 4-month follow-up, a new measurable nodule was found [Figure 3]d, which was considered as PD according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 standard (The RECIST Working Group). The patient stopped taking apatinib and S-1 after suffering from cerebral infarction in October 2018.
Figure 3: Efficacy of S-1 and apatinib after the treatment in patient one. (a) Before the apatinib and S-1 treatment. (b) Treatment with S-1 plus apatinib for 1-month. The tumor was partially detached and the lesions significantly shrunk. (c) After the 3-month treatment with S-1 plus apatinib, the tumor continuously shrunk. (d) After the 4-month treatment with S-1 plus apatinib, one new measurable nodule was observed

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The patient experienced moderate high blood pressure and mild hand-foot syndrome, which were well controlled after appropriate treatment; no severe toxicities and other treatment-related adverse events were observed.

Patient two, a 46-year-old man, visited the hospital with chief complaints of local mass and pain in the left neck in July 2018. The patient underwent puncture biopsy. Pathological diagnosis confirmed metastatic squamous cell carcinoma, whereas nasopharyngeal carcinoma was suspected on the basis of immunohistochemical examination [Figure 4]. However, nasopharyngoscope, CT, and positron emission tomography-CT findings did not reveal the primary lesion. Two-cycle chemotherapy with TP regimen (docetaxel and nedaplatin) was administered.
Figure 4: The patient was diagnosed with metastatic squamous cell carcinoma; nasopharyngeal carcinoma was inferred based on immunohistochemical examination. (H and E, ×400)

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In September 2018, neck and chest CT was performed. CT results revealed a neck mass that is much larger than the baseline diameter [Figure 5]a and [Figure 5]c. He refused to receive further vein chemotherapy due to chemotherapeutic toxicity, including nausea, vomiting, and leukopenia.
Figure 5: The efficacy of S-1 and apatinib after treating patient 2. (a) Before the treatment of apatinib and S-1. (b) After the 2-month treatment with S-1 plus apatinib, the measurable neck lesion was almost flat. (c) Curative effect observation with computed tomography was observed before the treatment of apatinib and S-1. (d) After the 2-month treatment with S-1 plus apatinib, the neck tumor was significantly narrowed

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Most cells also showed strong positive staining for VEGFR-2 [Figure 6]. Therefore, the treatment was changed to apatinib and S-1. Apatinib was administered at 425 mg daily and S-1 at 60 mg twice daily. After 15 days, the neck tumor was markedly reduced.
Figure 6: Expressions of vascular endothelial growth factor receptor 2 in a tumor section in patient two strong positive staining for vascular endothelial growth factor receptor 2 was found in cancer cells (IHC, ×400)

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During the 1-month follow-up, the measurable neck lesion was almost flat, which was considered as PR according to the RECIST 1.1 standard. After the 2-month treatment with S-1 plus apatinib, the tumor continuously shrunk [Figure 5]b and [Figure 5]d. No new measurable lesion was observed, which considered SD according to the RECIST 1.1 standard.

With the exception of mild hand-foot syndrome, gum swelling and pain; and oral mucosa ulceration, (which were well controlled after appropriate treatment), no severe toxicities and treatment-related adversities were observed. The patient continuously used apatinib and S-1 as maintenance therapy.

Patient three, a 71-year-old man, visited the hospital with chief complaints of oropharyngeal pain in July 2018. The patient underwent puncture biopsy. Pathological diagnosis confirmed squamous cell carcinoma of the pyriform sinus [Figure 7]. Four-cycle chemotherapy with TP regimen (docetaxel and nedaplatin) was administered.
Figure 7: The patient was diagnosed with squamous cell carcinoma of the pyriform sinus (H and E, ×400)

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In October 2018, the neck and chest CT was performed after four-cycles of chemotherapy, which revealed that the oropharyngeal mass became larger than its baseline size [Figure 8]a. He refused to receive further vein chemotherapy due to chemotherapeutic toxicity, including vomiting and leukopenia.
Figure 8: Curative effect observation with computed tomography in patient three. (a) Before the treatment of apatinib and S-1. (b) Treatment with S-1 plus apatinib after 1 month

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Most cells also showed strong positive staining for VEGFR-2 [Figure 9]. Therefore, the treatment was changed to apatinib and S-1. Apatinib was administered at 425 mg daily and S-1 at 60 mg twice daily. A month later, the oropharyngeal tumor was markedly reduced [Figure 8]b, which was considered as PR according to the RECIST 1.1 standard.
Figure 9: Expressions of vascular endothelial growth factor receptor 2 in a tumor section in patient three Strong positive staining for vascular endothelial growth factor receptor 2 was found in cancer cells (IHC, ×400)

Click here to view


With the exception of mild hand-foot syndrome, no severe toxicities and treatment-related adversities were observed. The patient continuously used apatinib and S-1 as maintenance therapy.


 > Discussion Top


Platinum-based chemotherapy is the usual first-line treatment for inoperable, recurrent, or metastatic squamous cell carcinoma of the head and neck (SCCHN); however, its results are far from satisfactory.[14] Platinum combined with docetaxel as induction treatment yields high ORR and CR in unresectable SCCHN cases.[15],[16] Therefore, the TP regimen used as the first-line treatment.

Head and neck cancer cells often express the epidermal growth factor receptor (EGFR).[17] Cetuximab is an IgG1 monoclonal antibody that inhibits ligand binding to the EGFR 5–7. In 2006, the Food and Drug Administration confirmed cetuximab as the only effective drug for patients with recurrent/metastatic SCCHN who did not receive platinum therapy.[18] In the first-line therapy, adding cetuximab to cisplatin improves the response rate compared with cisplatin alone. Cetuximab has shown a good regional-targeting advantage in randomized trials in many countries and can increase the survival rate of patients with SCCHN by 9% (45.6% vs. 36.4%).[19] However, cetuximab is very expensive. These two patients cannot afford its cost.

Apatinib is an oral small-molecule anti-angiogenesis inhibitor that plays an anti-tumor role by selectively inhibiting the phosphorylation of ATP binding sites in VEGFR-2 expressing cells, thereby blocking downstream signal transduction.[20] Considering the high expression level of VEGFR-2 in the tumor section of patients one and two, apatinib was recommended. Moreover, the cost of apatinib is one-third to that of cetuximab. Thus, patients one and two chose apatinib after careful consideration. Considering that many studies have reported the effectiveness of fluorouracil for the treatment of head and neck tumors, apatinib combined with S-1 was administered in these patients. For patients one and two, during the 15-day follow-up following apatinib and S-1 treatment, PR was met according to the RECIST 1.1 standard. For these three patients, during the 1-month follow-up, the measurable neck lesion continuously shrunk. However, PD was observed at the 4-month follow-up in patient one. For patient one, he stopped taking apatinib and S-1 after suffering a cerebral infarction. In addition, all patients lived without severe toxicity or drug-related side effects.


 > Conclusion Top


Apatinib may be used as an additional treatment option for advanced head and neck neoplasms. Combined with our findings, the efficacy and safety of apatinib in patients with advanced head and neck neoplasms should be further assessed in large-scale prospective studies.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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[PUBMED]  [Full text]  
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Kim R, Hahn S, Shin J, Ock CY, Kim M, Keam B, et al. The effect of induction chemotherapy using docetaxel, cisplatin, and fluorouracil on survival in locally advanced head and neck squamous cell carcinoma: A Meta-analysis. Cancer Res Treat 2016;48:907-16.  Back to cited text no. 14
    
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Mesía R, Vázquez S, Grau JJ, García-Sáenz JA, Lozano A, García C, et al. Aphase 2 open label, single-arm trial to evaluate the combination of cetuximab plus taxotere, cisplatin, and 5-flurouracil as an induction regimen in patients with unresectable squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 2016;94:289-96.  Back to cited text no. 15
    
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9]



 

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