Clinical Study Of Metronomic Chemotherapy With Cisplatin And Radiotherapy For Stage Ⅱ-Ⅳ Nasopharyngeal Carcinoma

Objective: Metronomic chemotherapy is a sustainable therapeusiswith low dose (usually1/10-1/3MTD) of standard chemotherapy, its key linkis anti-angiogenesis of tumor, it different from conventional chemotherapywith predominantly cytotoxic effect. Nasopharyngeal carcinoma is one of thecommon malignant tumors in China and radiation therapy is the main treatmentof it.A large number of clinical studies have demonstrated platinum drugschemotherapy combined radiotherapy can make the tumor local control ratesincreased from54%to78%. At present, the middle-late nasopharyngealcarcinoma patients are recommended to use cisplatin40mg/m2per weekcombined radiotherapy over the same period of radiation and chemotherapyscheme, but because of its toxicity is obvious,patients with difficult totolerate that affect curative effect.The metronomic chemotherapy as a way ofanti tumor vascular treatment,because of its low toxicity and good patients’compliance as well as anti-angiogenesis effect and other advantages, andradiation therapy combined with radiotherapy sensitization effect can beproduced, raise tumor local control rate, eventually to increase its curativeeffect.In the experiment, nasopharyngeal carcinoma as the main researchobject.Metronomic chemotherapy with cisplatin combined radiotherapy the Ⅱ-Ⅳ stage of nasopharyngeal carcinoma. It is well know that cisplatin is usedcommonly in head and neck squamous cell carcinomas.Compare these twotreatment mode in middle-late stage nasopharyngeal carcinoma which eitherMetronomic chemotherapy of cisplatin,8mg/m2(twice a week) combinedradiotherapy (Early clinical dose climbing experiment has confirmed twice aweek the metronomic cisplatin chemotherapy combined radiotherapy forlocally middle-late maximum tolerated dose of nasopharyngeal carcinoma(NPC) is8mg/m2) or concurrent chemoradiotherapy weekly cisplatin40mg/m2.Then, to investigate clinical curative effect and adverse reactions as well astolerability of metronomic chemotherapy with cisplatin and radiotherapy innasopharyngeal carcinoma.Method: A total of35patients with nasopharyngeal carcinoma conforming tothe standard from May2012to Jan.2014were divided into two groups:metronomic chemotherapy group (15patients) and concurrentchemoradiotherapy (20patients). When all patients were treated by6MV-X rayintensity-modulated radiotherapy, patients with metronomic chemotherapy weregiven cisplatin8mg/m2twice a week synchronously; patients with concurrentchemoradiotherapy were given cisplatin40mg/m2per week synchronously. Weobserve clinical curative effect, toxicities and treatment compliance. Then weevaluate tolerability by considering adverse reactions and treatment completionand we evaluate antitumor vessel effect by comparing changes of lesionsmicrovascular perfusion before and after therapy through CT perfusion imaging.1. Result:1. Acute toxicity incidence comparison of two group, nausea/vomiting rate is lower in metronomic chemotherapy group; nausea/vomiting,toxicity in oral mucosa and pharynx/esophagus are significant differencebetween metronomic chemotherapy group and control group throughcomparing acute toxicity grade, while there is no significant difference in latetoxicities and short-term therapeutic effect.2. Comparing tolerability, there is agood tolerability in the metronomic chemotherapy group as this group wasgiven cisplatin ten times, which completed the76.9%dose. There is a mediumtolerability in the control group as this group was given cisplatin four times,which completed the66.7%dose.3. The parameters of normal pharynx wallhave no obvious change in both two groups comparing perfusion imagingbefore and after therapy. In lesions, parameters of CT perfusion imaging: BF,BV, PS decline and MTT rise, Similar to normal tissue. Otherwise, the degreeof improvement in the metronomic chemotherapy group is more obvious thanthe control group.2. Conclusion:1.By comparing the cisplatin metronomic chemotherapycombined radiotherapy with the cisplatin concurrent chemoradiotherapy,thetwo groups of short-term therapeutic effect is similar, but the metronomicchemotherapy group is better than control group in acute toxicity,tolerance andcompliance;2.the degree of improvement comparison of nasopharyngeal lesionand normal pharyngeal wall tissues, parameters of CT perfusion: BF, BV, PS decline and MTT rise in metronomic chemotherapy combined radiotherapy andconcurrent chemoradiotherapy. Otherwise, the improved degree is moreobvious in the metronomic chemotherapy group.