【摘要】：目的:鼻咽癌(nasopharyngeal carcinoma,NPC)是中國廣東及沿海地區(qū)最常見的頭頸部惡性腫瘤。含順鉑的同期放化療(CCRT)是局部晚期鼻咽癌(LA-NPC)的標(biāo)準(zhǔn)治療方法,但順鉑所致惡心嘔吐、粘膜等副作用明顯,可能導(dǎo)致患者中斷治療,影響療效。有研究發(fā)現(xiàn)新一代化療藥多西他賽作為同期化療方案,其療效不劣于順鉑且副作用較小。但這些結(jié)果均來自小樣本的回顧性研究,目前缺乏前瞻性的研究。放射性口腔粘膜炎是鼻咽癌同期放化療中最主要的副作用之一。放射性口腔粘膜炎目前尚無有效的治療方法及藥物。近年來中醫(yī)中藥尤其是滋陰清熱類中藥在減輕放化療副作用上具有一定的療效。增液湯是滋陰類方劑的代表之一。有研究顯示增液湯可減輕放化療的口腔粘膜反應(yīng),但相關(guān)研究較少,在此方基礎(chǔ)上加味應(yīng)用能否減輕放療過程中口腔黏膜炎仍有待研究證實�；谝陨蠁栴},設(shè)計了本研究。采用前瞻性隨機研究方法,對比多西他賽和順鉑應(yīng)用于鼻咽癌同期放化療的近期療效及副作用,旨在探討多西他賽能否作為順鉑的替代化療藥物,以期為鼻咽癌患者提供更多高效低毒的化療方案選擇。同時本研究在放療過程中配合服用加味增液湯方,以期明確加味增液湯在防治鼻咽癌放化療期間對放射性口腔粘膜炎的作用,為降低放化療副作用,提高治療依從性提供有效的中藥方劑。方法:篩選2015年3月3日至2017年2月15日廣州軍區(qū)總醫(yī)院腫瘤科初治的局部晚期鼻咽癌患者81例,所有患者先行3周期誘導(dǎo)化療,再行同期放化療。誘導(dǎo)化療方案為多西他賽(TXT)75 mg/m2、順鉑(DDP)80 mg/m2,每3周一次。放療采用三維適形放療(3D-CRT),DT:70Gy/35f。放療開始后隨機分為兩組,研究組采用多西他賽同期化療(方案為75mg/m2/3周),對照組采用順鉑同期化療(方案為40mg/m2/周×7次或80mg/m2/3周×3次)。放療期間,兩組中分別隨機選取患者口服加味增液湯。觀察放化療期間急性放射性口腔黏膜炎等副反應(yīng)發(fā)生情況,治療結(jié)束后3個月評價其療效。結(jié)果:所有患者均完成放化療。1例患者在治療過程中病情進展,80例可評價近期療效。兩組近期療效相當(dāng)(CR率分別為73.3%vs.72.0%;PR率分別為26.7%vs.28.0%,P0.05)。副作用方面,TXT組放療過程中1-3級放射性口腔黏膜炎發(fā)生率分別為10.0%、56.7%、33.3%;DDP組放療過程中1-3級放射性口腔黏膜炎發(fā)生率分別為2.0%、37.3%、60.8%,兩組均無4級放射性口腔粘膜炎發(fā)生。TXT組放射性口腔黏膜炎程度較輕,差異有統(tǒng)計學(xué)意義(P=0.011)。TXT組和DDP組放射性口腔粘膜炎發(fā)生時間分別出現(xiàn)在放療后11.63±3.68天、9.76±3.57天,TXT組口腔粘膜炎發(fā)生時間較晚(t=2.249、P=0.027)。多因素分析顯示:同期化療藥物是3度口腔粘膜炎發(fā)生的獨立影響因素(OR=0.324,P=0.034)。性別、年齡、T分期、N分期、總臨床分期、放療同時是否口服中藥均不是3級放射性口腔炎發(fā)生的顯著影響因素(P0.05)。TXT組1-3級放射性皮炎的發(fā)生率分別為56.7%、30.0%、13.30%;DDP組1-3級放射性皮炎的發(fā)生概率分別為49.0%、43.1%、7.8%(P=0.723),兩組比較差異無統(tǒng)計學(xué)意義。DDP組惡心嘔吐的發(fā)生率高于TXT組(91.2%vs.56.7%,P=0.001)。多因素分析顯示:同期化療藥物是2-3級惡心嘔吐的影響因素(OR=0.272,P=0.026)。兩組在放化療期間各等級骨髓抑制發(fā)生率無統(tǒng)計學(xué)差異(戶0.05)。多因素分析顯示同期化療藥物多西他賽(P=0.016)、男性(P=0.029)是影響貧血發(fā)生的獨立影響因素。非中藥組放射性口腔粘膜炎發(fā)生率為1級1.9%、2級38.5%、3級59.6%;中藥組放射性口腔粘膜炎發(fā)生率為1級10.3%、2級55.2%、3級34.5%,中藥組放射性口腔黏膜炎程度低于非中藥組,差異有統(tǒng)計學(xué)意義(P=0.019)。結(jié)論:在局部晚期鼻咽癌同步放化療中,多西他賽與順鉑單藥同期化療的近期療效相當(dāng)。TXT組放射性黏膜炎及胃腸道反應(yīng)更小,患者耐受性可,有可能成為順鉑同期化療替代藥物之一。放療期間口服加味增液湯可減輕放射性口腔黏膜炎,提高患者耐受性和治療依從性。
[Abstract]:Objective: Nasopharyngeal carcinoma (NPC) is the most common head and neck malignancy in Guangdong and coastal areas of China. The concurrent chemoradiotherapy with cisplatin (CCRT) is the standard treatment for locally advanced nasopharyngeal carcinoma (LA-NPC), but the side effects such as nausea, vomiting and mucosa caused by cisplatin are obvious, which may lead to discontinuation of treatment and affect the curative effect. As a concurrent chemotherapy regimen, docetaxel, a new generation of chemotherapeutics, has been found to be no less effective than cisplatin and has fewer side effects. However, these results are based on a small sample of retrospective studies, and there is no prospective study. Radioactive oral mucositis is one of the major side effects of concurrent radiotherapy and chemotherapy for nasopharyngeal carcinoma. In recent years, traditional Chinese medicine, especially Ziyin Qingre herbal medicine, has a certain effect on reducing the side effects of radiotherapy and chemotherapy. Zengye decoction is one of the representatives of Ziyin decoction. Some studies have shown that Zengye decoction can reduce the oral mucosal reaction of radiotherapy and chemotherapy, but there are few related studies. Based on the above questions, a prospective randomized study was designed to compare the short-term efficacy and side effects of docetaxel and cisplatin in concurrent radiotherapy and chemotherapy for nasopharyngeal carcinoma. The purpose of this study is to clarify the effect of Jiawei Zengye Decoction on the prevention and treatment of radioactive oral mucositis during radiotherapy and chemotherapy of nasopharyngeal carcinoma, and to provide effective Chinese medicine for reducing the side effects of radiotherapy and chemotherapy and improving the compliance of treatment. METHODS: 81 patients with locally advanced nasopharyngeal carcinoma were selected from March 3, 2015 to February 15, 2017 in the Department of Oncology, General Hospital of Guangzhou Military Region. All patients received three cycles of induction chemotherapy followed by concurrent radiotherapy and chemotherapy. The induction chemotherapy regimen was docetaxel (TXT) 75 mg/m2, cisplatin (DDP) 80 mg/m2, once every three weeks. D-CRT, DT:70Gy/35f. Patients were randomly divided into two groups at the beginning of radiotherapy. The study group received concurrent chemotherapy with docetaxel (75mg/m2/3 weeks) and the control group received concurrent chemotherapy with cisplatin (40mg/m2/week x 7 or 80mg/m2/3 weeks x 3 times). During radiotherapy, patients in the two groups were randomly selected to take Jiawei Zengye Decoction. Results: All patients completed radiotherapy and chemotherapy. One patient progressed in the course of treatment, and 80 patients could evaluate the short-term efficacy. The short-term efficacy of the two groups was similar (CR rate was 73.3% vs. 72.0%; PR rate was 26.7% vs. 28.0%, P 0.05). The incidence of Grade 1-3 radiation oral mucositis was 10.0%, 56.7% and 33.3% in group DDP and 2.0%, 37.3% and 60.8% in group DDP. There was no grade 4 radiation oral mucositis in both groups. The degree of radiation oral mucositis in group TXT was mild, and the difference was statistically significant (P = 0.011). The onset time of radiation-induced oral mucositis in TXT group and DDP group were 11.63 (+ 3.68) and 9.76 (+ 3.57) days after radiotherapy respectively. The onset time of radiation-induced oral mucositis in TXT group was later (t = 2.249, P = 0.027). Multivariate analysis showed that the concurrent chemotherapy drugs were the independent influencing factors (OR = 0.324, P = 0.034). Sex, age, T stage, N stage, total. The incidence of Grade 1-3 radiodermatitis in TXT group was 56.7%, 30.0% and 13.30% respectively, and that in DDP group was 49.0%, 43.1% and 7.8% (P = 0.723), respectively. The incidence of cardiac vomiting was higher than that of TXT group (91.2% vs. 56.7%, P = 0.001). Multivariate analysis showed that the concurrent chemotherapy drugs were the influencing factors of grade 2-3 nausea and vomiting (OR = 0.272, P = 0.026). There was no significant difference in the incidence of bone marrow suppression between the two groups (household 0.05). Multivariate analysis showed that the concurrent chemotherapy drug docetaxel (P = 0.016), male. The incidence of radiation-induced oral mucositis in non-traditional Chinese medicine group was 1.9%, 38.5% and 59.6% respectively; the incidence of radiation-induced oral mucositis in traditional Chinese medicine group was 10.3%, 55.2% and 34.5% respectively. The degree of radiation-induced oral mucositis in traditional Chinese medicine group was lower than that in non-traditional Chinese medicine group (P = 0.019). Conclusion: Docetaxel and cisplatin have similar short-term effects in concurrent chemoradiotherapy for locally advanced nasopharyngeal carcinoma. Radioactive mucositis and gastrointestinal tract reactions in TXT group are less severe, and patients can tolerate it. It may be one of the substitutes for cisplatin in concurrent chemoradiotherapy. Improve patient tolerance and treatment compliance.
【學(xué)位授予單位】：廣州中醫(yī)藥大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R739.63
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本文編號：2178521