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ORIGINAL ARTICLE
Year : 2016  |  Volume : 12  |  Issue : 5  |  Page : 47-49

Evaluating the efficacy and safety of continuous arterial infusion chemotherapy with cisplatin and 5-fluorouracil in treating oral cancer


1 Department of Stomatology, Lishui People's Hospital, The 6th Affiliated Hospital of Wenzhou Medical University, Zhejiang, Lishui 323000, PR China
2 Department of Radiology, Lishui People's Hospital, The 6th Affiliated Hospital of Wenzhou Medical University, Zhejiang, Lishui 323000, PR China

Date of Web Publication7-Oct-2016

Correspondence Address:
Junjie Yan
Department of Stomatology, Lishui People's Hospital, The 6th Affiliated Hospital of Wenzhou Medical University, Zhejiang, Lishui 323000
PR China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.191629

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 > Abstract 


Objective: To investigate the clinical effects and safety for cisplatin combined with 5-fluorouracil (5-FU) intra-arterial chemotherapy in the treatment of oral cancer.
Materials and Methods: A total of ninety cases with oral cancer were recruited in this study. Forty-three subjects received the pingyangmycin (PYM) (control group) with PYM 8 mg, intramuscular injection, QD for 21 days per cycle. Moreover, other 47 cases received cisplatin 100 mg/m 2 24 h perfusion chemotherapy, day 1 with 21 days per cycle, and 5-FU 1000 mg/m 2 perfusion chemotherapy 72 h with 21 days per cycle. All the patients received three cycles treatment. After three cycles chemotherapy, the objective response rate (ORR) and chemotherapy-related toxicities were evaluated between the two groups.
Results: The ORR were 53.49% and 72.34%, respectively in the control and observation group which indicated observation group significant higher (P < 0.05). The chemotherapy-related toxicities incidence was much higher in control group compared with observation group (36.17% vs. 11.63%, P < 0.05).
Conclusion: Cisplatin combined with 5-FU intra-arterial chemotherapy was effective in the treatment of oral cancer with less toxicties.

Keywords: 5-fluorouracil, chemotherapy, cisplatin, continuous arterial infusion, oral cancer


How to cite this article:
Ye M, Li X, Liu W, Tao H, Yan J. Evaluating the efficacy and safety of continuous arterial infusion chemotherapy with cisplatin and 5-fluorouracil in treating oral cancer. J Can Res Ther 2016;12:47-9

How to cite this URL:
Ye M, Li X, Liu W, Tao H, Yan J. Evaluating the efficacy and safety of continuous arterial infusion chemotherapy with cisplatin and 5-fluorouracil in treating oral cancer. J Can Res Ther [serial online] 2016 [cited 2018 Aug 16];12:47-9. Available from: http://www.cancerjournal.net/text.asp?2016/12/5/47/191629




 > Introduction Top


Most of the early stage oral cancer patients are willing to undergo surgery for good prognosis, whereas patients with advanced stage of lymphatic metastasis required chemotherapy treatment.[1] Chemotherapy is an important method for treating oral cancer, and chemotherapy drugs mainly include pingyangmycin (PYM), cisplatin, 5-fluorouracil (5-FU), and others. Pharmacokinetic studies show that the efficacy of chemotherapy is related to the drug concentration; that is, by doubling the drug concentration in chemotherapy, the number of killed tumors cells can increase 10-fold.[2] Therefore, increasing the effective drug concentration is a key to enhancing the efficacy of chemotherapy. Conventional drugs for intravenous administration enter the systemic circulation system, with a relatively low drug concentration at the tumor site. Drug concentration is enhanced by increasing the dose, but the toxic reaction of the chemotherapy drug increases sharply with the increased rate of the chemotherapy drug. Thus, conventional intravenous chemotherapy cannot effectively improve local tumor drug concentration, which is a bottleneck that restricts chemotherapy efficacy in tumors.[3] Continuous regional arterial infusion chemotherapy can improve the efficacy of chemotherapy in treating oral cancer, with less systemic adverse reactions.[4] Therefore, in this study, more ideal clinical effects were obtained by continuous arterial infusion chemotherapy with cisplatin and 5-FU after the retrograde catheterization of the superficial temporal artery as shown below.


 > Materials and Methods Top


Case selection

A total of ninety patients admitted to our hospital with oral cancer were selected as the subjects and investigated on the approval of the Ethics Committee of our hospital. Informed consent forms were signed by the patients or their family members.

Inclusion criteria

Patients aged over 18 years old that were pathologically diagnosed with oral squamous cell carcinoma, with normal hepatic and renal functions, and have undergone chemotherapy with PYM, cisplatin, and 5-FU.

Exclusion criteria

A history of allergies to PYM, cisplatin, and/or 5-FU, with a score exceeding two points in the physical fitness test, an expected survival of <3 months or pregnancy.

Treatment regime

Ninety patients with oral cancer were divided into the control group (43 cases) and the experimental group of 47 (cases). The control group received 8 mg PYM intramuscularly, once a day, 21 days per cycle. Through the use of microflow syringe pumps, the experimental group was arterially infused at 21 days per cycle with 100 mg/m 2 cisplatin over 24 h, with a continuous 72 h 1000 mg/m 2 5-FU infusion on date 1, and the procedures were repeated after 3 weeks. All the patients of the two groups received three chemotherapy cycles.

Clinical evaluation criteria

Clinical evaluation criteria mainly include the following: (1) complete response (CR): With lesions having completely disappeared, (2) partial response (PR): With more than 50% focal narrowing by the dual path product, (3) stable disease (SD): With more than 25% focal narrowing by the dual path product or the emergence of new foci, (4) progressive disease (PD): With focal narrowing by the dual path product hardly passing PR or the extent of new foci falling short of PD. Objective response rate (ORR) = CR + PR. Adverse reactions, including hematological toxicity, gastrointestinal reactions, and others were observed in the two groups during chemotherapy.

Statistical analysis

SPSS 17.0 software (http://www-01.ibm.com/software/analytics/spss/) is used for statistical analysis. The count data are expressed by a rate, and the between-group comparison is tested by Chi-square test.


 > Results Top


General information

Ninety patients admitted to our hospital with oral cancer were selected as subjects for investigation. Among these cases, 43 of the control group were intramuscularly administered with PYM, and 47 cases among the experimental group received continuous regional arterial infusion chemotherapy with cisplatin and 5-FU. [Table 1] shows the general information on the two groups. The two groups are comparable, without statistical significances in the gender, median age, and pathological grading (P > 0.05).
Table 1 The general information for the two gorups

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Clinical efficacies

After three chemotherapy cycles, the clinical efficacies of the control group included 11 cases with CR, 12 with PR, 16 with SD, and 4 with PD, and the ORR was 53.49%. In the experiment group, 17 cases with CR, 18 with PR, 10 with SD, and 2 with PD were observed, and the ORR was 72.34%. The ORR of the experiment group was significantly higher than that of the control group, with statistical significance (P < 0.05) [Table 2].
Table 2: The clinical efficacy comparison of the two groups, n (%)

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Safety evaluation

The total incidence of adverse reactions in the experimental group was 11.63%, whereas that in the control group was 36.17%, which is significantly higher compared with the control group (P < 0.05).


 > Discussions Top


Epidemiological investigations revealed that the incidence of oral cancer exhibits an increasing trend.[5],[6],[7] The etiology of oral cancer is currently unclear; most studies have linked the incidence of oral cancer to a long history of smoking and/or alcohol consumption, and the incidence among that population is higher than that of the nonsmoking and/or nonalcohol consumption population. Early stage patients treated with surgery had relative good prognosis, but patients with advanced oral cancer often attain poorer prognosis and require adjuvant chemotherapy. PYM is often administered intramuscularly in conventional oral cancer chemotherapy. However, clinical studies have shown that clinical efficacy is extremely limited and exhibit higher incidence of adverse reactions.[8] Recent studies show that higher chemotherapy efficacy in treating oral cancer can be achieved by the local arterial administration for the catheterization of the superficial temporal artery. Pharmacokinetic studies have shown that local drug concentration can be increased by the arterial administration in treating tumors, and the concentration is geometrically related to the efficacy of chemotherapy. In theory, when the drug concentration increases twofold, the concentration was doubled or increased by 100%. Therefore, the efficacy of chemotherapy can be improved by the chemotherapy regimen by using catheterization of the superficial temporal artery.

The studies confirm that cisplatin, a drug with cell cycle specificity, kills tumor cells depending on the drug concentration. After arterial administration, high-concentration cisplatin can directly reach the tumor site, thereby improving chemotherapy efficacy significantly. 5-FU, a typical cycle-specific drug, acts by inhibitory effects on the generation and synthesis of cellular DNA and by mitosis. However, the drug acts only during a cell cycle. Thus, a high level should be maintained within a long period to participate in killing more tumor cells involved in the proliferation stage. After continuous arterial infusion with a microflow syringe pump, the drug functions in long uninterrupted chemotherapy. Cisplatin shows enhanced efficacy with the biochemical modulation of 5-FU, and a combination of the two drugs exhibits a synergistic effect. In this study, the overall clinical response rate of the experimental group is 72.34%, which is consistent with the results in other related studies.[9],[10] In addition, the total incidence of adverse reactions in the experiment group is revealed to be lower than that in the control group. The results suggest that good efficacy of continuous regional arterial infusion chemotherapy was obtained, improving the cash reserve ratio while lowering the incidence of adverse reactions.


 > Conclusion Top


Significant efficacy is achieved by continuous regional arterial infusion chemotherapy in treating oral cancer, with a lower incidence of adverse reactions. Therefore, this chemotherapy regime is worth applying and promoting in clinical practice.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 > References Top

1.
de Visscher JG. Treatment and prognosis of oral cancer. Ned Tijdschr Tandheelkd 2008;115:192-8.  Back to cited text no. 1
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2.
Patel K, Foster NR, Farrell A, Le-Lindqwister NA, Mathew J, Costello B, et al. Oral cancer chemotherapy adherence and adherence assessment tools: A report from North Central Cancer Group Trial N0747 and a systematic review of the literature. J Cancer Educ 2013;28:770-6.  Back to cited text no. 2
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Buglione M, Cavagnini R, Di Rosario F, Sottocornola L, Maddalo M, Vassalli L, et al. Oral toxicity management in head and neck cancer patients treated with chemotherapy and radiation: Dental pathologies and osteoradionecrosis (Part 1) literature review and consensus statement. Crit Rev Oncol Hematol 2016;97:131-42.  Back to cited text no. 3
    
4.
Ohbayashi Y, Miyake M, Iwasaki A, Ogawa T, Nagahata S, Toyama Y, et al. Clinical study of the area under the blood concentration-time curve of targeting intra-arterial infusion chemotherapy with nedaplatin for primary oral cancer. Gan To Kagaku Ryoho 2004;31:41-4.  Back to cited text no. 4
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Krishna Rao SV, Mejia G, Roberts-Thomson K, Logan R. Epidemiology of oral cancer in Asia in the past decade – An update (2000-2012). Asian Pac J Cancer Prev 2013;14:5567-77.  Back to cited text no. 5
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Lambert R, Sauvaget C, de Camargo Cancela M, Sankaranarayanan R. Epidemiology of cancer from the oral cavity and oropharynx. Eur J Gastroenterol Hepatol 2011;23:633-41.  Back to cited text no. 6
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Tohnai I. Chemotherapy using intra-arterial infusion for oral cancer. Nagoya J Med Sci 2006;68:101-8.  Back to cited text no. 7
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8.
Shudo A, Kishimoto H. Oral management during cancer chemotherapy – Imperative role of dentistry and oral surgery. Nihon Rinsho 2015;73 Suppl 2:673-7.  Back to cited text no. 8
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Yamshita Y, Shikimori M, Goto M. Clinical trial of chemotherapy by superselective intra-arterial infusion of nedaplatin combined with radiotherapy for advanced oral cancer. Gan To Kagaku Ryoho 2005;32:1267-71.  Back to cited text no. 9
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Iwasaki A, Toyama Y, Saitou H, Ohkubo N, Imagawa N, Ogawa T, et al. Targetting intra-arterial infusion chemotherapy with nedaplatin for oral cancer. Gan To Kagaku Ryoho 2001;28:1027-33.  Back to cited text no. 10
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  [Table 1], [Table 2]



 

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