【摘要】 目的同步放化疗是局部进展期宫颈癌和无法手术切除早期宫颈癌的标准治疗,紫杉醇(PTX)联合顺铂(DDP)是同步放疗常用的化疗方案。本研究通过药物剂量递增试验,明确原发宫颈癌每周PTX和DDP同步三维适形盆腔放疗的最大耐受剂量(maximum tolerated dose,MTD)。方法选取2008-10-18-2013-05-15北京大学第三医院经病理学确诊的FIGO分期为ⅠB1~ⅣA的腹主动脉旁淋巴结阴性的初治原发宫颈癌患者18例。盆腔采用6、10 MV X射线,4个野三维适形外照射,照射剂量为50~50.4Gy/25~28次,其中在36~40Gy予盆腔中央挡铅,根据病情继续予宫旁加量10~20 Gy/5~10次;192Ir高剂量率腔内照射,A点剂量为6 Gy/次,共6~8次。化疗DDP剂量为每周40mg/m2保持不变,PTX分为每周10、20、30、40和50mg/m2 5个剂量组,共6个周期。每组3例患者,第5剂量组为剂量限制性不良反应(does-limiting toxicity,DLT)组,共6例患者。结果 18例患者中位年龄46.5岁(32~66岁),均在8周内完成外照射和腔内照射。在前4个剂量组中,1例(第1剂量组)在拟行第6个周期化疗前1d出现2级非粒细胞减少性发热(菌血症性发热),伴3级恶心呕吐和电解质紊乱停化疗,完成5个周期化疗;其余11例完成6个周期化疗。在第5剂量组的6例患者中,1例出现4级白细胞减少,另外3例均因为出现3级白细胞减少无法恢复至正常导致化疗延迟2周以上中断化疗,仅有1例按时完成6个周期的化疗。结论原发宫颈癌三维适形盆腔照射联合每周PTX和DDP化疗的最大耐受剂量为6个周期的每周PTX 40mg/m2和DDP 40mg/m2,该方案具有安全性和可行性。更多还原

【Abstract】 OBJECTIVE To determine the maximum tolerated dose(MTD)weekly PTX plus DDP concurrent with whole pelvic irradiation in Chinese women with primary cervical cancer.METHODS Consenting patients with stage ⅠB1,ⅡA,ⅡB,ⅢB and ⅣA carcinoma of the cervix(all cell types)were eligible for this trial.All patients received 3D conformal radiation therapy to the pelvis(50-50.4Gy in 25-28fractions)followed by 6-8fractions/6Gy/weekly of high dose rate brachytherapy.Concurrent chemotherapy was administered with weekly cisplatin(40mg/m2)and an escalating dose of weekly paclitaxel starting at 10mg/m2 up to 50mg/m2.Chemotherapy agents were administered in escalating doses to cohorts of three patients at each dose level.RESULTS Eighteen patients with primary cervical carcinoma were enrolled into this trial.The MTD was confirmed to be paclitaxel 40 mg/m2 and cisplatin 40 mg/m2 administered weekly for six cycles with 3Dconformal external beam radiotherapy.3/3patients completed all of chemotherapy and radiotherapy without grade 3toxicities in 7weeks at the MTD level.In 6patients at a dose of 50mg/m2 weekly paclitaxel,1had grade 4leukopenia,and 3who had grade 3leukopenia could not complete chemotherapy because white blood cells failed to return normal levels in two weeks.CONCLUSION Combination PTX and DDP administered concurrently with3 Dconformal pelvic EBRT can be safely administered at the MTD of DDP 40mg/m2 and PTX 40mg/m2 weekly for six cycles in Chinese women.更多还原