卡培他滨联合调强放疗治疗乳腺癌肝转移的疗效观察

 目的 探讨卡培他滨联合调强放疗（intensity modulated raduation therapy, IMRT）并序贯卡培他滨治疗乳腺癌肝转移的疗效和不良反应。方法 将52例乳腺癌肝转移患者分为卡培他滨联合放疗组27例和卡培他滨治疗组25例。卡培他滨联合放疗组肝转移灶行IMRT,6 MV-X线照射,以95％剂量曲线包绕99%计划靶区,常规分割,2 Gy/次,1次/d,5次/周,共  4～6周,同时给予卡培他滨1 250 mg/m²,2次/d口服同步化疗,放疗结束后给予卡培他滨2 510 mg/m²,2次/d口服,21 d为1个周期。卡培他滨治疗组仅给予卡培他滨2 510 mg/m²,2次/d口服,21 d为1个周期。比较两组疗效及不良反应。结果 卡培他滨联合放疗组和卡培他滨治疗组有效率（RR）分别为74.1%和44%,肿瘤控制率分别为92.6%和68%,两组比较差异均有统计学意义（P>0.05）;中位缓解时间分别为13.6个月和8.9个月,中位生存时间分别为17.4个月和11.7个月,1年生存率分别为85.2%和56.0% (χ²=5.38,P,2年生存率分别为40.7%和16.0% (χ²=3.84,P＜0.05)。不良反应主要有中性粒细胞减少、胃肠道反应、肝功能损伤等,均以Ｉ级、Ⅱ级为主,卡培他滨联合放疗组Ｉ级、Ⅱ级不良反应发生率高于卡培他滨治疗组（P＜0.05）,但两组Ⅲ级、Ⅳ级不良反应发生率差异无统计学意义（P>0.05）。结论 卡培他滨联合调强放疗并序贯卡培他滨治疗乳腺癌肝转移远期生存率优于单药卡培他滨维持治疗,不良反应可耐受,是一种有效的治疗方案。     

三维适形放疗同步卡培他滨化疗治疗老年胃癌

目的:研究三维适形放疗同步卡培他滨化疗治疗老年胃癌患者的疗效、生存时间和不良反应。方法:本院收治的45例老年胃癌患者随机分为卡培他滨单药化疗组（21例）和三维适形放疗同步卡培他滨化疗组（24例）。PTV剂量1.8Gy/(25f·5w),放疗开始同步卡培他滨化疗。比较两组患者的疗效、生存时间和不良反应。结果:卡培他滨单药化疗组客观缓解率61.9%,三维适形放疗同步卡培他滨化疗组客观缓解率87.5%,有显著统计学差异(P＜0.05)。两组不良反应、生活质量无显著差异。卡培他滨单药化疗组2年生存率23.8%,三维适形放疗同步卡培他滨化疗组2年生存率50.0%,有显著统计学差异(P＜0.05)。结论:三维适形放疗同步卡培他滨化疗治疗老年胃癌可以有效提高患者的治疗效果,改善预后,不良反应可以耐受,是一种安全有效的治疗方案。     

三维适形放疗联合卡培他滨治疗子宫颈癌腹主动脉旁淋巴结转移的临床观察

目的 探讨三维适形放疗联合卡培他滨治疗子宫颈癌腹主动脉旁淋巴结转移的短期效果和患者不良反应.方法 56例子宫颈癌腹主动脉旁淋巴结转移患者分为单纯放疗组和三维适形放疗联合卡培他滨组（联合治疗组）,每组各28例,两组患者均给予三维适形放疗,2Gy/次,每周5次,腹主动脉旁总剂量60Gy.联合治疗组在三维适形放疗第1天起给予卡培他滨1 250 mg/m2,每日2次,第1天至第14天,休息7d为1个周期,行2个周期同步化疗,观察临床效果和不良反应.结果 单纯放疗组的总有效率为57.1％（16/28）,联合治疗组的总有效率为82.1％（23/28）,两组总有效率差异有统计学意义（P＜0.05）.治疗过程中的不良反应大部分患者均可耐受,经对症处理后均得以缓解.结论 卡培他滨联合三维适形放疗能够增强子宫颈癌腹主动脉旁淋巴结转移的近期疗效.     

全脑放疗联合尼莫司汀同步化疗治疗实体肿瘤脑转移的临床观察

目的：观察全脑放疗联合尼莫司汀同步化疗治疗实体肿瘤伴多发脑转移的疗效及不良反应。方法：对39例实体肿瘤脑转移患者分别采用全脑放疗联合尼莫司汀同步化疗和单纯全脑放疗方案治疗。同步放化疗组：全脑照射（WBRT）为DT2Gy/次,5次/周,总剂量40Gy。放疗开始的第1天同时给予尼莫司汀（ACNU）,2mg/kg,d1,每4-6周重复,共使用2-4个疗程。单纯放疗组：全脑照射（WBRT）为DT 2Gy/次,5次/周,总剂量40Gy。放疗结束后3个月评价疗效。结果：同步放化疗组总有效率65.0%（13/20）高于单纯放疗组（42.1%,8/19）;神经系统症状改善情况,同步放化疗组优于单纯放疗组;不良反应以放疗脑充血水肿及尼莫司汀引起的骨髓抑制和胃肠道反应为主。结论：全脑放疗联合尼莫司汀同步化疗治疗实体肿瘤脑转移的近期疗效、神经系统症状改善情况优于单纯放疗,不良反应可耐受,可作为实体肿瘤脑转移患者的解救方案。     

三维适形放疗同步卡培他滨化疗治疗直肠癌术后复发的临床观察

 目的　观察直肠癌术后复发三维适形放疗同步口服卡培他滨的疗效及不良反应。方法　选择64例直肠癌术后复发患者,随机分为三维适形放疗同步口服卡培他滨组（32例,治疗组）和三维适形放疗组（32例,对照组）。卡培他滨1250 mg／m2,每天2次口服,从放疗开始的第1天口服,连续服用14 d,休息1周,21 d为1个周期。同步进行的三维适形放疗,DT 60～70 Gy,2 Gy／次,5次／周,放疗结束后3个月复查盆腔CT。结果　治疗组总有效（CR+PR）率为87.6 %,对照组总有效率为65.6 %。结论　三维适形放疗同步口服卡培他滨治疗直肠癌术后复发的患者,疗效确切,不良反应小。     

放化综合治疗在脑转移癌治疗中的临床应用研究

目的:观察放化综合治疗脑转移癌的近期疗效与安全性。方法:62例脑转移癌患者随机分为放化疗组与单纯放疗组。其中化疗联合组31例,非小细胞肺癌脑转移患者入组替莫唑胺联合放疗组、乳腺癌脑转移患者入组卡培他滨联合放疗组;31例为单纯放疗组。替莫唑胺联合放疗组给予替莫唑胺[75mg/(m2·d)]至放疗结束,卡培他滨组给予[625mg/(m2·d),2次/d,连用4周]。两组均联合2周三维适形头部放疗,总剂量42Gy(3Gy,5f/w),其中全脑30Gy/10f,病灶区补量12Gy/4f;单纯放疗组仅予42Gy三维适形头部放疗,其中全脑30 Gy,病灶区补量12 Gy。联合放化疗组放疗结束后继续给予2个周期替莫唑胺[每周期150mg/(m2·d)],连续服用5d,28d为1个周期;卡培他滨组给予[每周期825mg/(m2·d),2f/d,d1-14],连续服用14d,28d为1个周期。结果:联合放疗组与单纯放疗组的客观有效率分别为80.63%、64.5%,差异无统计学意义(P>0.05);骨髓抑制发生率分别为70.96%、54.84%,胃肠道毒副反应发生率分别为61.29%、41.94%,差异均无统计学意义(P>0.05)。结论:替莫唑胺联合放疗以及卡培他滨联合放疗治疗非小细胞肺癌及乳腺癌脑转移安全、有效,但是近期疗效对比单纯放疗差异不显著。     

卡培他滨同步放疗治疗术前局部晚期低位直肠癌的临床观察

 目的　观察卡培他滨同步放疗治疗术前局部晚期低位直肠癌的临床疗效及患者不良反应。方法　回顾性分析局部晚期低位直肠癌患者30例,随机平均分为两组。对照组放疗采用6 MV-X直线加速器,剂量为45.0～50.4 Gy、25～28次,进行35～38 d,平均剂量45 Gy;观察组在放疗基础上同步加用卡培他滨1250 mg／m2,2次口服,第1天至第14天,第22天至第35天,中间休息1周。两组患者均治疗结束后4～6周进行手术。结果　观察组治疗后的根治性切除率为100 %（15／15）,病理完全缓解（pCR）率20.00 %（3／15),保肛率53.33 %（8／15）。对照组分别为73.33 %（11／15）、6.67 %（1／15)、13.33（2／15）,两组比较差异均有统计学意义（χ2＝3.564、4.028、6.18,P＝0.033、0.026、0.008）。远期疗效观察组便血和疼痛缓解持续中位时间为15个月,对照组为8个月,两组比较差异有统计学意义（χ2＝4.822,P＝0.012）。观察组术后1、2、3、5年生存率明显优于对照组,差异有统计学意义（均P<0.05）。结论　对于局部晚期低位直肠癌患者,术前卡培他滨同步放疗可以提高手术切除率、保肛率,降低局部复发率,且不良反应轻。     

三维适形放疗同步联合吉西他滨和卡培他滨化疗治疗原发性肝癌的疗效

目的:探讨三维适形放疗同步联合吉西他滨和卡培他滨化疗治疗不能手术切除的原发性肝癌的疗效和不良反应.方法:给予41例不能手术切除的原发性肝癌患者三维适形放疗,放射剂量为2～3 Gy/次、1次/d、5次/周,总剂量50～60 Gy,放疗同时给予吉西他滨联合卡培他滨方案化疗2个周期.结果:全组41例患者完全缓解5例、部分缓解30例、疾病稳定5例、疾病进展1例,总有效率为85.4%,1年生存率80.4%、2年生存率为58.5%,中位生存期24.8个月.最常见的不良反应为骨髓抑制、胃肠反应、肝功能损害和手足综合征,均可耐受.结论:三维适形放疗同步联合吉西他滨和卡培他滨化疗治疗对不能手术切除的原发性肝癌具有较好的疗效,且不良反应可以耐受.     

全脑放疗联合尼莫司汀同步化疗治疗实体肿瘤脑转移的临床观察

目的:观察全脑放疗联合尼莫司汀同步化疗治疗实体肿瘤伴多发脑转移的疗效及不良反应。方法:对39例实体肿瘤脑转移患者分别采用全脑放疗联合尼莫司汀同步化疗和单纯全脑放疗方案治疗。同步放化疗组:全脑照射(WBRT)为DT2Gy/次,5次/周,总剂量40Gy。放疗开始的第1天同时给予尼莫司汀(ACNU),2mg/kg,d1,每4-6周重复,共使用2-4个疗程。单纯放疗组:全脑照射(WBRT)为DT 2Gy/次,5次/周,总剂量40Gy。放疗结束后3个月评价疗效。结果:同步放化疗组总有效率65.0%(13/20)高于单纯放疗组(42.1%,8/19);神经系统症状改善情况,同步放化疗组优于单纯放疗组;不良反应以放疗脑充血水肿及尼莫司汀引起的骨髓抑制和胃肠道反应为主。结论:全脑放疗联合尼莫司汀同步化疗治疗实体肿瘤脑转移的近期疗效、神经系统症状改善情况优于单纯放疗,不良反应可耐受,可作为实体肿瘤脑转移患者的解救方案。     

三维适形放疗结合卡培他滨化疗治疗直肠癌手术后骶前复发病灶

 目的　观察三维适形放疗结合卡培他滨化疗治疗对直肠癌术后骶前复发病灶的疗效及不良反应。方法　47例直肠癌手术后骶前复发患者,给予三维适形放射治疗、常规分割照射局部DT 5200～6800 Gy,同时口服卡培他滨每天2000 mg／m2,每日2次口服,连服14 d,休7 d,21 d为1个周期,至少完成4个周期。结果　随访2年以上,完全缓解（CR）率12.8 %（6／47）,部分缓解（PR）率51.1 %（24／47）,总缓解率63.9 %。症状改善：会阴酸胀下坠缓解率100 %（30／30）,局部疼痛总缓解率80 %（20／25）,出血缓解率84.6 %（11／13）。1、2年生存率为66 %、34 %。未出现严重的不良反应。结论　卡培他滨与放疗同步治疗直肠癌手术后骶前复发病灶是一种安全、局部控制率高、不良反应可耐受的治疗手段,明显改善患者生存质量。     

SRT联合拉帕替尼治疗HER2阳性乳腺癌脑转移疗效及预后分析

目的 探讨立体定向放射治疗(Stereotactic radiotherapy,SRT)联合拉帕替尼治疗HER2阳性乳腺癌脑转移的疗效及预后。方法 回顾性分析91例HER2阳性乳腺癌脑转移患者接受拉帕替尼靶向治疗的同时接受全脑放疗或SRT的情况,其中42例患者接受SRT的同时进行拉帕替尼联合卡培他滨治疗(SRT组),另外49例患者采用全脑放疗同时进行拉帕替尼联合卡培他滨治疗(全脑放疗组)。评价其疗效和毒性,定期随访,并行多因素Cox回归分析其预后相关因素。结果 放疗结束后1月SRT组脑部病灶客观缓解率为92.86%(39/42),全脑放疗组客观缓解率为77.55%(38/49),SRT组优于全脑放疗组(χ²=4.070,P=0.044)。SRT组和全脑组12个月受照射肿瘤病灶无进展生存率分别为95.20%及83.10%, SRT组优于全脑放疗组(χ²=10.851,P=0.001)。 SRT组无颅内转移生存率与全脑放疗组无统计学差异(P＞0.05)。SRT组和全脑放疗组1年生存率分别为85.70%和69.40%,2年生存率分别为66.70%和55.10%,两组中位生存期分别为31.56个月和25.00个月,SRT组优于全脑放疗组(P=0.002)。多因素Cox回归分析结果表明无颅外转移(HR=0.527,95% CI:0.290~0.957,P=0.035),颅内病灶≤3个(HR=2.457,95% CI:1.223~4.933,P=0.012),放疗方式SRT(HR=1.746,95% CI:1.055~2.888,P=0.030)是HER2阳性乳腺癌脑转移放疗预后的独立保护因素。结论 SRT联合拉帕替尼在局部控制率以及生存率上优于全脑放疗联合拉帕替尼。颅内病灶个数少、无颅外转移灶和放疗方式是HER2阳性乳腺癌脑转移治疗的良好预后因素。     

A phase 2 trial of whole-brain radiotherapy combined with intravenous chemotherapy in patients with brain metastases from breast cancer

BACKGROUND

A study was conducted to determine the efficacy, tolerability, and safety of concurrent cisplatin and vinorelbine chemotherapy and radiotherapy in patients with previously untreated brain metastases from breast cancer.

METHODS

Twenty‐five patients with untreated brain metastases from breast cancer were treated with cisplatin (at a dose of 20 mg/m²/day, Days 1‐5) and vinorelbine (6‐mg/m² bolus on Day 1 and 6 mg/m²/day continuous infusion on Days 1‐5) chemotherapy combined with concurrent 30‐gray fractionated external‐beam radiotherapy. Chemotherapy was given at 3‐week intervals for a total of 4 cycles. Primary endpoint was the rate of radiologic response of brain metastases.

RESULTS

Complete response in the brain was observed in 3 patients, and partial response was noted in 16 patients, yielding a 76% response rate in the brain. The overall systemic response rate was 44%. Progression‐free and overall survival were 3.7 months and 6.5 months, respectively. Overall toxicity was acceptable; nonhematologic grade 3‐4 events were noted in 5 (20%) patients, and there were no toxic deaths.

CONCLUSIONS

Concurrent chemoradiation with cisplatin and vinorelbine for brain metastases from breast cancer appears to be active and well tolerated. Cancer 2008. © 2008 American Cancer Society.     

低位直肠癌术前调强放疗同步加量并同步口服卡培他滨化疗的初步研究

目的探讨低位直肠癌调强放射治疗（IMRT）同步加量并同步口服卡培他滨化疗的毒副作用,并初步分析其疗效。方法回顾性分析16例接受术前IMRT同步加量放疗同时口服希罗达化疗,临床诊断为T_（2～4）和/或N_（1～2）的低位直肠腺癌患者,放射治疗采用5野IMRT技术,共25次5周,全盆腔45～50Gy,肿瘤及其周围2cm范围同步加量至55～60Gy。同时口服卡培他滨625mg/m~2,每日2次,应用2周后休息1周,再继续口服至放疗结束。手术于放疗结束后8～10周进行。记录分析所有病例的毒副作用及远近期疗效。结果所有病例顺利完成治疗,无治疗中断者。有11例患者（68.8%）出现Ⅲ度皮肤反应,无Ⅲ度以上腹泻、血液学及泌尿系统毒副作用,仅1例患者（6.3%）出现晚期Ⅱ度胃肠道毒副作用。放疗后评估临床完全缓解7例（43.8%）,部分缓解8例（50%）。12例（75%）患者保肛,其中手术并保肛7例,肿物消失拒绝手术5例。2年总生存率85.7%,无病生存率76.6%,局部复发率6.3%。结论低位直肠癌调强放射治疗（IMRT）同步加量并同步口服卡培他滨化疗有一定效果且患者耐受良好,值得进一步探索研究。     

Phase I/II study of preoperative cetuximab, capecitabine, and external beam radiotherapy in patients with rectal cancer.

BACKGROUND: To assess the safety and preliminary efficacy of concurrent radiotherapy, capecitabine, and cetuximab in the preoperative treatment of patients with rectal cancer. PATIENTS AND METHODS: Forty patients with rectal cancer (T3-T4, and/or N+, endorectal ultrasound) received preoperative radiotherapy (1.8 Gy, 5 days/week for 5 weeks, total dose 45 Gy, three-dimensional conformal technique) in combination with cetuximab [initial dose 400 mg/m(2) intravenous given 1 week before the beginning of radiation followed by 250 mg/m(2)/week for 5 weeks] and capecitabine for the duration of radiotherapy (650 mg/m(2) orally twice daily, first dose level; 825 mg/m(2) twice daily, second dose level). RESULTS: Four and six patients were treated at the first and second dose level of capecitabine, respectively. No dose-limiting toxicity occurred. Thirty additional patients were treated with capecitabine at 825 mg/m(2) twice daily. The most frequent grade 1/2 side-effects were acneiform rash (87%), diarrhea (65%), and fatigue (57%). Grade 3 diarrhea was found in 15%. Three grade 4 toxic effects were recorded: one myocardial infarction, one pulmonary embolism, and one pulmonary infection with sepsis. Two patients (5%) had a pathological complete response. CONCLUSIONS: Preoperative radiotherapy in combination with capecitabine and cetuximab is feasible with some patients achieving pathological downstaging.     

Neoadjuvant concurrent chemoradiotherapy with capecitabine and oxaliplatin in patients with locally advanced esophegeal cancer

Evaluation of the feasibility and efficacy of neoadjuvant concurrent chemoradiotherapy (CRT) with capecitabine and oxaliplatin in patients with locally advanced esophageal cancer. Forty-two patients were eligible for the study. The chemotherapy during CRT consisted of two cycles of intravenous oxaliplatin of 120 mg/m(2) on day 1 and oral capecitabine 825 mg/m(2) twice daily on days 1-14 at 3-week intervals. The radiotherapy (1.8 Gy/fraction/day to a total dose of 45 Gy) was delivered to the primary tumor site and regional lymph node. All patients completed the planned treatment. Overall clinical response rate was 54.8% with complete response in 16.7% while pathological response rate was 38%. Anemia was the commonest hematologic toxicity (52.3%) with grade 3 in 4.7%, and esophagitis was the commonest non-hematologic toxicity 59.5% with grade 3 and 4 in 9.5%. No treatment-related death was observed. After a median follow-up duration of 19 months, the 2-year survival rate was 42%, median survival time was 20 months (95%CI: 13.802-26.198), while 2-year progression-free survival (PFS) rate was 32.5% with median PFS time of 15 months (95%CI: 10.042-19.958). Neoadjuvant concurrent CRT with capecitabine and oxaliplatin was found to be well tolerated and effective in patients with locally advanced esophageal cancer; however, these results should be further evaluated in a phase III study.     

Postoperative chemoradiotherapy in gastric cancer -- a Phase I/II dose-finding study of radiotherapy with dose escalation of cisplatin and capecitabine chemotherapy

We hypothesised that gastric cancer outcome could be improved with more effective and intensified postoperative chemoradiotherapy. This phase I/II study was performed to determine the maximal tolerated dose (MTD) and toxicity profile of postoperative radiotherapy with concurrent daily cisplatin and capecitabine. Patients were treated with capecitabine 1000 mg m(-2) twice a day (b.i.d.) for 2 weeks. Subsequently, patients received capecitabine (250-650 mg m(-2) orally b.i.d., 5 days week(-1)) and cisplatin (3-6 mg m(-2) i.v., 5 days week(-1)) according to an alternating dose-escalation schedule. Radiotherapy was given to a total dose of 45 Gy in 25 fractions. Thirty-one patients completed treatment. During chemoradiotherapy, eight patients developed nine items of grade III and one episode of grade IV (mainly haematological) toxicity. The MTD was determined to be cisplatin 5 mg m(-2) i.v. and capecitabine 650 mg m(-2) b.i.d. orally. This phase I/II study demonstrated that chemoradiotherapy with daily cisplatin and capecitabine is feasible in postoperative gastric cancer at the defined dose level and is currently being tested in a phase III multicenter study.     

放化疗同步治疗肺癌脑转移38例临床分析

目的:观察长春瑞滨(NVB)、顺铂(DDP)加用卫萌(Vm-26)联合脑部放射治疗肺癌脑转移患者的疗效、不良反应和生存率。方法:Vm-260·1,静脉滴入,d1~d3;NVB25mg/m2,静脉滴入,d1、d8;DDP20mg/m2,静脉滴入,d1~d3;21d为1个周期,脑部放疗于第1个周期化疗开始后第5天开始,每次DT1·8~2·0Gy,1次/d,每周5次,1~2个病灶者全脑放疗DT40Gy后缩野追加至DT60Gy,≥3个转移灶者给予全颅放疗DT45Gy。结果:治疗后90%患者神经系统症状改善,对脑转移灶的客观有效率为71·1%(27/38),对肺原发灶的有效率为42·1%(16/38),主要不良反应为骨髓抑制和脱发,中位生存期11·01个月,1年生存率39·5%(15/38)。结论:同步放、化疗治疗肺癌脑转移患者有效率和生存率均较高,且患者耐受性好。肿瘤防治杂志,2005,12(19):1502-1504     

An EORTC phase I study of capecitabine (Xeloda) in combination with fixed doses of cyclophosphamide and epirubicin (cex) as primary treatment for large operable or locally advanced/inflammatory breast cancer

In breast cancer, chemotherapy regimens that include infusional 5-fluorouracil (5-FU) lead to high response rates, but require central venous access and pumps. To avoid these inconveniences, we substituted infusional 5-FU with capecitabine. The main objective of this study was to determine the maximum tolerated dose (MTD) of capecitabine when given in combination with fixed doses of epirubicin and cyclophosphamide (100 and 600 mg/m(2) day 1 every (q) 3 weeks) as primary treatment for large operable or locally advanced/inflammatory breast cancer without distant metastasis. Capecitabine was escalated from 750 mg/m(2) twice a day (bid) to 1250 mg/m(2) bid from day 1 to day 14 in four dose levels. Dose escalation was permitted if 0/3 or 1/6 patients experienced dose-limiting toxicity (DLT). A total of 23 patients were included and 117 courses were administered. At dose level 4, 2 of 2 patients presented DLTs defining the MTD. A high rate of capecitabine treatment modification was required with capecitabine 1050 mg/m(2) bid (dose level 3). 19 patients achieved an objective response (83%). In conclusion, we believe that capecitabine 900 mg/m(2) bid (dose level 2) is the recommended dose in combination with epirubicin 100 mg/m(2) and cyclophosphamide 600 mg/m(2). The acceptable toxicity profile and encouraging activity of this regimen warrant further evaluation.