|Year : 2016 | Volume
| Issue : 8 | Page : 252-255
Clinical efficacy and safety of gemcitabine plus nedaplatin in the treatment of advanced nasopharyngeal carcinoma
Yan Hu1, Jiang Tao Fu1, Dongmei Shi2, Biao Feng3, Zhichao Shi4
1 Department of Otolaryngology, Lishui People's Hospital, Lishui, Zhejiang, China
2 Department of Otolaryngology, People's Hospital of Xinjiang Urumqi Autonomous Region, Urumqi, Xinjiang, China
3 Department of Otolaryngology, Armed Police Corps Hospital, Xian, Shanxi, China
4 Department of Clinical Pharmacy, Lishui People's Hospital, Lishui, Zhejiang, China
|Date of Web Publication||22-Feb-2017|
Department of Clinical Pharmacy, Lishui People's Hospital, Lishui, 323000, Zhejiang
Source of Support: None, Conflict of Interest: None
Objective: The purpose was to explore the clinical effects and safety of gemcitabine plus nedaplatin in the treatment of advanced nasopharyngeal carcinoma.
Materials and Methods: From March 2014 to August 2015, we recruited 63 advanced nasopharyngeal carcinoma patients in our hospital. Moreover, the 62 cases were randomly divided into control group (n = 31) and treatment group (n = 32). Patients in the control groups were treated with 5-fluorouracil 500 mg/m 2 + 500 ml 0.9% sodium chloride injection intervenous drop infusion in day 1–5 plus cisplatin 20 mg/m 2 + 500 ml 0.9% sodium chloride injection intervenous drop infusion in day 1–5 with 21 days per cycle for 3 cycles; Moreover, patients in the treatment group were given gemcitabine 1000 mg/m 2 + 500 ml 0.9% sodium chloride injection intervenous drop infusion in day 1 and 8 plus nedaplatin 20 mg/m 2 + 500 ml 0.9% sodium chloride injection intervenous drop infusion in day 1 with 21 days per cycle for 3 cycles. The objective response rate (ORR) and chemotherapy-associated toxicities were compared between the two groups.
Results: After 3 cycle chemotherapy, the ORR was 41.9% and 78.1% in the control and treatment group, respectively, with statistical difference (P < 0.05); The main chemotherapy-related toxicity were hematological toxicity and gastrointestinal reaction with no statistical difference between the two groups (P > 0.05).
Conclusion: The ORR was relative high for gemcitabine plus nedaplatin in the treatment of advanced nasopharyngeal carcinoma with main toxicity of hematological toxicity and gastrointestinal reaction.
Keywords: Advanced nasopharyngeal carcinoma, chemotherapy, clinical efficacy, gemcitabine, nedaplatin, toxicities
|How to cite this article:|
Hu Y, Fu JT, Shi D, Feng B, Shi Z. Clinical efficacy and safety of gemcitabine plus nedaplatin in the treatment of advanced nasopharyngeal carcinoma. J Can Res Ther 2016;12:252-5
|How to cite this URL:|
Hu Y, Fu JT, Shi D, Feng B, Shi Z. Clinical efficacy and safety of gemcitabine plus nedaplatin in the treatment of advanced nasopharyngeal carcinoma. J Can Res Ther [serial online] 2016 [cited 2017 May 30];12:252-5. Available from: http://www.cancerjournal.net/text.asp?2016/12/8/252/200750
| > Introduction|| |
Nasopharyngeal carcinoma is a common malignant head and neck tumor in our country. The incidence of this disease exhibits typical regional characteristics, and a relatively higher incidence is found in Guangdong, Guangxi, Hunan, and Fujian than in other areas in China., Nasopharyngeal carcinoma affects males, with a male-to-female ratio of approximately 2.5:1. A high disease incidence is also found in individuals aged 40–50 years. Nevertheless, the prognosis of nasopharyngeal carcinoma is relatively good. A high 5-year survival rate can also be achieved in patients in early stages after combined therapy is administered. In contrast to prognosis in early stages, prognosis in advanced stages is poor; as such, patients in advanced stages are subjected to conservative treatment with radiotherapy. Chemotherapeutic drugs, such as 5-fluorouracil and cis-platinum, are commonly used to treat patients with advanced nasopharyngeal carcinoma.,, Gemcitabine is a water-soluble deoxycytidine analog used as an anticancer drug with 2-fluorine nucleoside antimetabolite., This drug is also a good surrogate of the inhibitory substrate for ribonucleoside diphosphate reductase, which is necessary to create the required deoxycytidine. nedaplatin, as a new platinum anticancer drug, is often used as a chemotherapeutic agent to treat tumors in the head, neck, and lungs because of its low toxicity and clinical effectiveness., The clinical data of patients who suffered from advanced nasopharyngeal carcinoma and received gemcitabine combined with nedaplatin are summarized in this report.
| > Materials and Methods|| |
A total of 63 patients who suffered from advanced nasopharyngeal carcinoma and admitted in the ENT department of the 6th People's Hospital affiliated to Wenzhou Medical University (Lishui People's Hospital) from March 2013 to August 2014 were included in the analysis. Informed consent forms were signed by patients and their family members. The study was approved by the Medical Ethical Committee.
Patients were included if the following conditions were satisfied: (1) performance status score were 0–2; (2) definite pathological diagnosis of nasopharyngeal carcinoma; (3) normal hepatorenal function; (4) no contraindications for chemotherapy; and (5) >3 months estimated survival time. The following exclusion criteria were considered: (1) severely insufficient heart, liver, or kidney functions; (2) same chemotherapeutic treatments received previously; (3) manifestations of multiple intracranial metastatic lesions; and (4) absence of evaluable lesions.
Medicines and devices
Gemcitabine (Ze Fei ™; 1000 mg/vial) was manufactured by Jiangsu Hansoh Pharmaceutical Co., Ltd. Nedaplatin (Lu Bei ™; 10 mg/vial) was obtained from Qilu Pharmaceutical Co., Ltd. A 16-row-spiral computed tomography system (GE, USA) and an automatic biochemistry analyzer (Roche, Switzerland) were used in this study.
Grouping and treatment plan
The included patients were randomly divided into the control group (n = 31) and the treatment group (n = 32) randomly by tossing a coin. The control group was treated as follows: 500 mg/m 2 5-fluorouracil + 500 ml of 0.9% NaCl intravenous glucose tolerance test (IVGTT) at day 1–5 and 20 mg/m 2 cis-platinum + 500 ml of 0.9% NaCl IVGTT at day 1–5. Chemotherapy was performed for three cycles, where one cycle was equal to 21 days. The treatment group was treated as follows: 1000 mg/m 2 gemcitabine + 500 ml of 0.9% NaCl IVGTT at day 1 and day 8 and 20 mg/m 2 nedaplatin + 500 ml of 0.9% NaCl IVGTT at day 1. The chemotherapy cycle was 21 days with all patients received 3 cycles.
Therapeutic effect and evaluation criteria
The objective remission rate and adverse reactions to chemotherapy were observed after chemotherapy was performed for 3 cycles. The objective response rate (ORR) was classified in accordance with the WHO standard: complete remission, all targeted lesions disappeared; partial remission (PR), the total long diameters of the baseline lesion was reduced by ≥30%; stable disease (SD), the long diameters of the baseline lesion were reduced, but PR was not reached or the long diameters were further reduced. Progressive disease (PD): the total long diameters of the baseline lesion were increased by ≥20%, or new lesions were presented; ORR = complete response + partial response; and adverse reactions were classified into 0–4 grades on the basis of WHO evaluation criteria for anticancer drugs.
Data were statistically analyzed using SAS 9.0.(http://www.sas.com/en_us/home.html) x¯ ± s was used to represent the measured data. Test and control groups were compared through Student's t-test. A relative number was used to represent the objective remission rate as one-way ordinal variable. The groups were also compared through a Chi-square test.
| > Results|| |
The clinical baseline data of the patients in treatment and control groups are shown in [Table 1]. The general conditions were not significantly different between the patients in both groups (P > 0.05).
Objective response rate
After 3 cycle chemotherapy, the ORR was 41.9% and 78.1% in the control and treatment group, respectively, with statistical difference (P < 0.05) [Table 2].
The main chemotherapy-related toxicity was hematological toxicity and gastrointestinal reaction with no statistical difference between the two groups (P > 0.05) [Table 3].
| > Discussion|| |
Several types of malignant tumors can be detected in the nasopharynx, but >99% of these tumors are carcinomas; most of these carcinomas are poor differentiated or undifferentiated. Approximately 80% of patients with nasopharyngeal carcinoma worldwide are documented in Guangdong, Guangxi, and southern provinces in China. Nasopharyngeal carcinoma in European and American countries is classified as a relatively rare tumor with an incidence of approximately 1/100,000. Epidemiologic studies have shown that the incidence of nasopharyngeal carcinoma increases among patients aged >30 years; the peak incidence is reached among the age of 50–60 years. Moreover, the incidence of this disease is significantly higher in males than in females.
A relatively low differentiation level is observed in most nasopharyngeal carcinomas, which are relatively susceptible to chemotherapeutic drugs. The prognosis for early nasopharyngeal carcinoma is better than that for advanced nasopharyngeal carcinoma. The combination of radiotherapy and chemotherapy is administered to most patients with advanced stages. General chemotherapeutic drugs with clinical effects include cis-platinum, carboplatin, 5-fluorouracil, and bleomycin. Gengshegn et al. reported the clinical effects of a 2-week 5-fluorouracil treatment. At least two treatment courses were administered to the patients. Complete response was observed in two patients (10%), partial response was found in 12 patients (60%), and SD was detected in 6 patients. No PD was recorded during treatment. No treatment-related death occurred. Primary chemotherapy-related drug adverse reaction included nausea, vomiting, and phlebitis. A higher remission rate with a lower toxicity was observed in patients with local advanced nasopharyngeal carcinoma treated with a 2-week therapy of cis-platinum combined with 5-fluorouracil.
Gemcitabine is the analog of cytarabine, which is an antimetabolite in the cell cycle. This drug can be inserted into DNA double strands to prevent DNA from replication and to reach antitumor targets. Nedaplatin is a second-generation platinum antitumor drug. The action mechanism of this drug is similar to that of cis-platinum. A nucleotide-platinum complex can be formed to bind to the DNA of a tumor cell and DNA replication is prevented to cause cell death and to reach antitumor targets. Baofang  used gemcitabine combined with nedaplatin to treat advanced nasopharyngeal carcinoma and evaluated the clinical effects and safety of the treatment program. Baofang  obtained excellent treatment effects and less chemotherapy drug-related toxicity when gemcitabine combined with nedaplatin is used to treat advanced nasopharyngeal carcinoma. A higher objective reaction rate is also determined when gemcitabine combined with nedaplatin is used to treat advanced nasopharyngeal carcinoma. The primary toxicities included hematological toxicity and gastrointestinal tract reaction, and the reaction is relatively mild. Therefore, gemcitabine combined with nedaplatin can be recommended for the chemotherapy of patients with advanced nasopharyngeal carcinoma which can improve its clinical effects and reduce toxicities.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| > References|| |
Chua ML, Wee JT, Hui EP, Chan AT. Nasopharyngeal carcinoma. Lancet 2016;387:1012-24.
Wei KR, Yu YL, Yang YY, Ji MF, Yu BH, Liang ZH, et al.
Epidemiological trends of nasopharyngeal carcinoma in China. Asian Pac J Cancer Prev 2010;11:29-32.
Yu WM, Hussain SS. Incidence of nasopharyngeal carcinoma in Chinese immigrants, compared with Chinese in China and South East Asia: Review. J Laryngol Otol 2009;123:1067-74.
Cao SM, Simons MJ, Qian CN. The prevalence and prevention of nasopharyngeal carcinoma in China. Chin J Cancer 2011;30:114-9.
Paiar F, Di Cataldo V, Zei G, Pasquetti EM, Cecchini S, Meattini I, et al.
Role of chemotherapy in nasopharyngeal carcinoma. Oncol Rev 2012;6:e1.
Baujat B, Audry H, Bourhis J, Chan AT, Onat H, Chua DT, et al.
Chemotherapy as an adjunct to radiotherapy in locally advanced nasopharyngeal carcinoma. Cochrane Database Syst Rev 2006;18:CD004329.
Hsieh JC, Hsu CL, Ng SH, Wang CH, Lee KD, Lu CH, et al.
Gemcitabine plus cisplatin for patients with recurrent or metastatic nasopharyngeal carcinoma in Taiwan: A multicenter prospective Phase II trial. Jpn J Clin Oncol 2015;45:819-27.
Peng PJ, Ou XQ, Liao H, Liu YM, Wang SY, Cheng ZB, et al
. Phase II study of gemcitabine plus S-1 chemotherapy in recurrent and metastatic nasopharyngeal carcinoma patients after failure of platinum-based chemotherapy Ther Adv Med Oncol 2016;8:153-9.
Peng PJ, Lv BJ, Tang C, Liao H, Lin Z, Liu YM, et al.
Phase II trial of docetaxel combined with nedaplatin for patients with recurrent and metastatic nasopharyngeal carcinoma. Drug Des Devel Ther 2015;9:6401-5.
Yin L, Wu J, Wu J, Ye J, Jiang X, Chen M, et al.
Radiosensitization effect of nedaplatin on nasopharyngeal carcinoma cells in different status of Epstein-Barr virus infection. Biomed Res Int 2014;2014:713674.
Neel HB 3rd
. Nasopharyngeal carcinoma: Diagnosis, staging, and management. Oncology (Williston Park) 1992;6:87-95.
Yu MC. Nasopharyngeal carcinoma: Epidemiology and dietary factors. IARC Sci Publ 1991;105:39-47.
Gengshegn Y, Youqian H, Yonghong H. Cisplatin and 5- fluorouracil/leucovorin combined therapy in the treatment of nasopharyngeal carcinoma: Preliminary report. Chin J Cancer 2001;8:873-5.
Baofang L. Clinical study of gemcitabine combined with nedaplatin in the treatment of advanced nasopharyngeal carcinoma. Hebei Med J 2014;16:2460-1.
[Table 1], [Table 2], [Table 3]