多西紫杉醇联合吡柔比星新辅助化疗治疗局部晚期乳腺癌临床疗效

目的观察多西紫杉醇联合吡柔比星在新辅助化疗治疗晚期乳腺癌的疗效及不良反应。方法 45例原发晚期乳腺癌患者采用多西紫杉醇联合吡柔比星方案,术前化疗2～4个周期,术后完成规定化疗,观察近期疗效及不良反应。结果新辅助化疗临床疗效总有效率为88%,其中3例病理为完全缓解,主要不良反应为呕吐,粒细胞减少及脱发。结论多西紫杉醇联合吡柔比星新辅助化疗治疗晚期乳腺癌疗效显著,不良反应可耐受,是新辅助化疗治疗晚期乳腺癌的有效方案之一。     

晚期乳腺癌应用多西他赛联合卡培他滨行新辅助化疗的临床观察

目的探讨晚期乳腺癌应用TX（多西他赛联合卡培他滨）方案行新辅助化疗的效果及安全性。方法回顾性分析55例Ⅲ-Ⅳ期用TX方案行新辅助化疗的晚期乳腺癌的临床资料。结果新辅助化疗的总有效率为89.09%（49/55）,有67.27%（37/55）的患者分期降低,患者的无病生存期平均为59.3个月,5年生存率为38.18%。新辅助化疗主要不良反应为胃肠道反应和骨髓抑制,多为Ⅰ级或Ⅱ级,Ⅲ/Ⅳ级不良反应主要为中性粒细胞减少（12.72%,7/55）和手足综合征（9.09%,5/55）,所有患者均无化疗相关性死亡。结论应用TX方案行新辅助化疗能降低晚期乳腺癌患者的分期,为手术创造最大机会,减少或延缓肿瘤复发、转移,并可延长晚期乳腺癌患者的无病生存期,不良反应可以耐受。     

去甲去氢长春花碱治疗42例晚期乳腺癌的近期疗效

目的：评价去甲去氢长春碱(诺维本NVB)对晚期乳腺癌的治疗作用。方法：采用诺维本为主药的联合方案，治疗晚期乳腺癌42例，均为初治患者，均经细胞学或病理证实。结果：本组完全缓解CR4例，部分缓解PR24例，有效率66．7％。主要毒性为骨髓抑制，及消化道反应。结论：NPC方案是治疗晚期乳腺癌较为理想的方案。     

洛铂联合方案治疗晚期乳腺癌的临床研究

目的探讨洛铂联合化疗方案在治疗晚期乳腺癌中的疗效与不良反应。方法收集2012年1月至2014年12月共52例晚期乳腺癌患者,予以洛铂联合化疗方案治疗,21~28d为1个周期。所有患者至少完成2个周期治疗,之后评价疗效及不良反应。结果无1例达到完全缓解(CR),部分缓解(PR)16例,疾病稳定(SD)21例,疾病进展(PD)15例,有效率(RR)为30.8%,疾病控制率(DCR)为71.2%。雌激素受体(ER)或人类表皮生长因子2(HER-2)阳性表达者与阴性表达者比较,RR差异均无统计学意义(P0.05)。一线治疗者与二线及以上治疗者比较,RR差异有统计学意义(P0.05)。三阴性乳腺癌患者中,乳腺癌易感基因1(BRCA1)突变者与BRCA1无突变者的DCR比较,差异有统计学意义(P0.05)。无内脏转移患者RR高于有内脏转移患者,差异有统计学意义(P0.05)。至随访日期止,46例患者为PD,中位疾病进展时间为6.5个月(95%置信区间为5.2~7.8个月)。主要不良反应为骨髓抑制、胃肠道反应等,多为0~Ⅱ度,经对症处理后可缓解,无治疗相关性死亡。结论洛铂联合化疗方案治疗晚期乳腺癌疗效较好,不良反应均可耐受。     

Vascularity change and tumor response to neoadjuvant chemotherapy for advanced breast cancer

For advanced breast cancer with severe local disease (ABC) (stage III/IV), neoadjuvant chemotherapy improves local control and surgical outcome. However, about approximately 20 to 30% of advanced cancers show either no or poor response to chemotherapy. To prevent unnecessary treatment, a capability of predicting clinical response to neoadjuvant chemotherapy of ABC is highly desirable. Vascularity index (VI) of breast cancers was derived from the quantification results in 30 ABC patients by using power Doppler sonography. Power Doppler sonography evaluation was performed every one to two weeks during chemotherapy. The overall response rate for 30 advanced patients tested was 70%, when 50% or more reduction in tumor size was the objective clinical response. Chemotherapy response was unrelated to the original tumor size (p = 0.563) or chemotherapy agents used (p = 0.657). The median VI for all 30 patients was 4.99%. The response rates for hypervascular tumors vs. hypovascular tumors, based on initial median value, were 86.7% and 53.3%, respectively (p = 0.109). The average VIs in responders and nonresponders were 7.67 +/- 4.77% and 4.01 +/- 3.82% (p = 0.052). There was a tendency for responders who have a relatively high initial vascularity. The VI change in responder group shows a pattern of initial increasing in vascularity followed by decreasing in vascularity. All patients (17/17) with a VI increment of >5% during chemotherapy had good chemotherapy response, whereas in patients with a VI increment of <5%, the response rate was 30.8% (4/13) (p < 0.001). For patients with a peak VI of >10% during chemotherapy, the response rate was 94.1% (16/17). However, in patients with a peak VI of <10%, the response rate was 38.5% (5/13) (p = 0.001). This prediction was made mostly within one month (25.47 +/- 12.96 d for VI increments >5% and 25.44 +/- 12.41 d for VI increased to >10%). In the meantime, the differences in size reduction shown in B-mode sonography were insignificant between responders and nonresponders (patient group with VI increment >5%, p = 0.308; patient group with peak VI >10%, p = 0.396). In conclusion, we propose that VI as determined by using power Doppler sonography is a good and inexpensive clinical tool for monitoring vascularity changes during neoadjuvant chemotherapy in ABC patients. Two parameters--VI increment >5% and peak VI >10%--are potential early predictors for good responses to neoadjuvant chemotherapy within one month in patients with ABC.     

Serum tumour markers CA 15-3, TPA, TPS, hCGbeta and TATI in the monitoring of chemotherapy response in metastatic breast cancer.

The clinical utility of CA 15-3, polypeptide specific antigen (TPS), tissue polypeptide antigen (TPA), human chorionic gonadotropin (hCGbeta) and tumour-associated trypsin inhibitor (TATI) as indicators of chemotherapy response was assessed in advanced breast cancer. Serum was prospectively collected in one center before treatment (after the first course of chemotherapy) and at response evaluation from 57 patients taking part in a multicentre randomized trial comparing docetaxel with sequential methotrexate and 5-fluorouracil in the treatment of advanced breast cancer. The pretreatment levels of the serum markers were not predictors of the later response to treatment. Changes in the TPS level showed the strongest association with clinical response after the first course of chemotherapy and CA 15-3 at the best response evaluation. However, distinct mismatches occurred with every marker. The most problematic error was an increase in marker levels in patients with clinical responses, which might have caused interruption of therapy. This occurred in 8% and 17% of patients after the first course of chemotherapy and in 4% and 17% of patients at the best response evaluation with CA 15-3 and TPS, respectively. Moreover, after the first course of chemotherapy only 39% and 33% of the patients with progressive disease could be identified on the basis of increasing levels of CA 15-3 and TPS. respectively. Later, at clinical disease progression, TPA and TPS were found to be better indicators of disease progression than CA 15-3. In conclusion, changes in CA 15-3 or TPS levels usually correlate with clinical response, but owing to distinct discordances, they should not be used as sole indicators of response to chemotherapy in advanced breast cancer.     

Serum tumour markers CA 15-3, TPA,TPS, hCG β and TATI in the monitoring of chemotherapy response in metastatic breast cancer

The clinical utility of CA 15-3, polypeptide specific antigen (TPS), tissue polypeptide antigen (TPA), human chorionic gonadotropin (hCGbeta) and tumourassociated trypsin inhibitor (TATI ) as indicators of chemotherapy response was assessed in advanced breast cancer. Serum was prospectively collected in one center before treatment (after the first course of chemotherapy) and at response evaluation from 57 patients taking part in a multicentre randomized trial comparing docetaxel with sequential methotrexate and 5-fluorouracil in the treatment of advanced breast cancer. The pretreatment levels of the serum markers were not predictors of the later response to treatment. Changes in the TPS level showed the strongest association with clinical response after the first course of chemotherapy and CA 15-3 at the best response evaluation. However, distinct mismatches occurred with every marker. The most problematic error was an increase in marker levels in patients with clinical responses, which might have caused interruption of therapy. This occurred in 8% and 17% of patients after the first course of chemotherapy and in 4% and 17% of patients at the best response evaluation with CA 15-3 and TPS, respectively. Moreover, after the first course of chemotherapy only 39% and 33% of the patients with progressive disease could be identified on the basis of increasing levels of CA 15-3 and TPS, respectively. Later, at clinical disease progression, TPA and TPS were found to be better indicators of disease progression than CA 15-3. In conclusion, changes in CA 15-3 or TPS levels usually correlate with clinical response, but owing to distinct discordances, they should not be used as sole indicators of response to chemotherapy in advanced breast cancer.     

赫赛汀联合多西紫杉醇用于局部晚期乳腺癌新辅助化疗近期疗效探讨

目的 探讨赫赛汀联合多西紫杉醇用于局部晚期乳腺癌新辅助化疗的近期疗效及不良反应.方法16例经病理证实为局部晚期乳腺浸润性导管癌患者接受赫赛汀(第1周期8 ms/kg,第2～4周期6ms/ks;静脉注射90 min,第1天)加多西紫杉醇(多西紫杉醇75 ms/m2静脉注射60 min,第2天)术前化疗,3周为1个周期,共4个周期;术前化疗后接受乳腺癌改良根治术或保乳根治术.结果 16例患者总有效率为87.5%,临床完全缓解率为56.3%,病理完全缓解率为25.0%;KPS评分均得到较大改善;主要不良反应为骨髓抑制和胃肠道反应,未出现心脏毒性.结论赫赛汀联合多西紫杉醇用于局部晚期乳腺癌新辅助化疗有较高的有效性和安全性,值得临床进一步探讨,最终结论需大样本的研究结果.     

紫杉醇联合顺铂治疗晚期乳腺癌32例分析

目的分析紫杉醇联合顺铂治疗晚期乳腺癌的疗效、毒性。方法32例晚期乳腺癌患者,应用紫杉醇联合顺铂治疗,化疗周期为21~30 d,中位治疗周期数为4(2~7)。紫杉醇中位剂量为162.5mg/m2(132.2~200.0 mg/m2);联合顺铂中位剂量74.5 mg/m2(67.5~85 mg/m2)。结果(1)全组患者有效率为40.6%,其中CR 1例,PR 12例,SD 15例,PD 4例(2)既往曾用过蒽环类药物患者有效率为45.8%;KPS评分70~80的有效率为33.3%,KPS评分90~100的有效率为45.0%。(3)肺转移患者的有效率为60.0%,肝转移患者的有效率为50.0%,软组织转移患者有效率为66.7%,而骨转移未见有效病例。(4)主要毒性反应为恶心呕吐和骨髓抑制。Ⅲ度和Ⅳ度恶心、呕吐发生率为5%。Ⅲ度和Ⅳ度白细胞减低发生率为75%,Ⅲ度和Ⅳ度血红蛋白减低发生率为25%;Ⅲ度和Ⅳ度血小板减低发生率为15%。结论紫杉醇联合顺铂治疗晚期乳腺癌疗效较好,毒性反应可以耐受。     

紫杉醇脂质体与多西紫杉醇对乳腺癌疗效及安全性临床观察

目的对比乳腺癌的新辅助化疗方案中紫杉醇脂质体与多西紫杉醇治疗效果和安全性的差异。方法对接受新辅助化疗后手术的乳腺癌174例患者的临床资料进行回顾性分析,根据患者自愿选择用药分为观察组（接受紫杉醇脂质体治疗）和对照组（接受多西紫杉醇治疗）,每组各87例,同时两组均给予环磷酰胺及表阿霉素的联合新辅助化疗方案,1个化疗周期为21天,共进行6个化疗周期,结束后过3周再给予手术切除,对两组的治疗效果及不良反应等进行统计分析。结果观察组的病理完全缓解率为10.3％（9/87）,客观缓解率分别为80.5％（70/87）,疾病控制率为95.4％（83/87）,对照组分别为9.2％（8/87）、79.3％（69/87）、93.1％（81/87）,两组比较差异均无统计学意义（P＞0.05）。观察组的白细胞减少（Ⅲ～Ⅳ级）、中性粒细胞减少（Ⅲ～Ⅳ级）、过敏反应、体液潴留、皮肤指甲毒性反应及口腔黏膜炎等的发生率均较对照组显著降低,差异均有统计学意义（均P＜0.05）。结论紫杉醇脂质体对于乳腺癌新辅助化疗的疗效与多西紫杉醇相近,但其化疗的不良反应发生率较低且程度轻,安全性要更高。     

Neoadjuvant chemotherapy for breast cancer determined by chemosensitivity assay achieves better tumor response.

BACKGROUND: Neoadjuvant chemotherapy can potentially reduce tumor size and help downstage the tumor before definitive operation was performed. However, it was not possible to tell whether the patient would respond to the regimen until given. This difficulty can be overcome by testing the susceptibility of a sample of cancer cells in vitro: a "patient-tailored approach". In this pilot study, we attempt to demonstrate an improved response by this "patient-tailored" approach over standard regimen. MATERIALS AND METHODS: The study included 36 women with moderately advanced local breast cancer larger than 2 cm in diameter. Twelve were allocated to receive a standard regimen of 5-fluorouracil, epirubicin and cyclophosphamide (FEC) preoperatively as controls, and 24 were given the most suitable regimen according to testing; the options were FEC, cyclophosphamide, methotrexate and 5-fluorouracil (CMF), 5-fluorouracil, adriamycin and mitomycin C (FAM) and paclitaxel alone. The cell activities of drug-treated solid tumors were compared to controls with a highly sensitive ATP bioluminescence assay. Patients received chemotherapy according to sensitivity results and the tumor area clinically measured before and after chemotherapy. RESULTS: Sensitivity-directed treatment helped patients achieve a higher rate of complete clinical response (10/24 vs. 0/12), larger mean reduction in tumor area (75% vs. 26%), and 25% pathological complete response (pCR). The paclitaxel subgroup achieved 80% (pCR). CONCLUSION: It is a useful in vitro assay to provide a reference of the particular patient who received treatment according to her sensitivity result. It may improve pathologic complete response, clinical tumor response and lead to less extensive surgery.     

亚甲基四氢叶酸还原酶基因多态性与乳腺癌化疗敏感性的关系

目的观察叶酸代谢的关键酶亚甲基四氢叶酸还原酶(MTHFR)基因C677T、A1298C多态与乳腺癌患者对化疗敏感性的关系。方法收集经病理学确诊的晚期乳腺癌患者61例,所有病例化疗前抽静脉血,提取白细胞DNA,用PCR-RFLP技术检测MTHFR基因型。接受6种不同的化疗方案化疗。结果61例乳腺癌癌患者中,MTHFR C/C基因型17例(27.9%)、C/T 29例(47.5%)、T/T 15例(24.6%)。MTHFR A1298C A/A基因型42例(68.9%),17例(27.9%)A/C基因型,2例(3.3%)C/C基因型。化疗总有效率为67.2%(41/61),其中CR3例(4.9%),PR38例(62.3%),SD15例(24.6%),PD5例(8.2%)。6种化疗方案的有效率无统计学差异(P=0.397)。MTHFR C/C基因型、C/T基因型、T/T基因型的有效率分别为58.8%、58.6%、93.3%,T/T基因型患者的有效率显著高于C/C基因型(P=0.041)和C/T基因型患者(P=0.034)。MTHFR A1298C A/A基因型、A/C基因型、C/C基因型的有效率分别为71.4%、64.7%、0.0%,MTHFR A1298C A/A基因型患者的有效率与A/C基因型(P=0.756)、C/C基因型患者之间无统计学差异(P=0.096)。结论本研究初步结果显示MTHFR C677T基因多态性对预测乳腺癌化疗疗效具有较好的临床应用价值。     

低剂量5-Fu静脉泵入治疗老年晚期胃癌疗效观察

目的观察低剂量5-Fu持续静脉泵入治疗老年晚期胃癌的疗效及毒副反应。方法 46例老年晚期胃癌患者,采用5-Fu 200 mg/(m2.d),静脉泵持续24 h点滴,连用14 d,21 d为1个周期。完成两个周期化疗后,评价疗效和毒副反应。结果临床总有效率为17.4%,其中CR 1例,PR 7例,SD 10例,PD 28例。近期疗效分析显示:转移病灶<3个的患者,客观缓解率(ORR)为31.6%,≥3个ORR为18.5%;KPS计分<80分的患者,ORR为10.7%,≥80分ORR为27.8%;进展时间(TTP)≥6个月的患者,ORR为30.8%,<6个月ORR为12.1%。毒副反应主要为口腔溃疡、恶心呕吐、腹泻等,多数为Ⅰ~Ⅱ级,对症处理后均缓解。结论 低剂量5-Fu持续静脉泵入方案临床疗效较好,毒副反应轻,适合于老年患者晚期胃癌的治疗。     

紫杉醇联合顺铂治疗78例晚期乳腺癌的近期疗效

目的：评价紫杉醇联合顺铂对晚期乳腺癌的治疗作用。方法：采用紫杉醇联合顺铂的联合方案，治疗晚期乳腺癌78例，均为初治患者，均经细胞学或病理证实。结果：本组完全缓解CR10．3％8例，部分缓解PR53．8％42例，(CR PR)有效率64％。主要毒性为骨髓抑制及消化道反应、结论：紫杉醇联合顺铂方案是治疗晚期乳腺癌较为理想的方案。     

乳腺癌新辅助化疗后残留癌组织的病理分析

目的探讨和分析乳腺癌新辅助化疗后残留癌组织变性区病理形态特点,为正确评价该治疗方法提供理论依据.方法应用病理形态学、免疫组化技术以及细胞凋亡检测技术(PCD)进行分析.结果10例导管浸润癌中有2例未找到残留癌组织,1例仅见少量残留癌组织,7例有不同程度癌组织残留.残留癌组织分为变性癌组织区(DCC)和非变性癌组织区(NDCC).比较两者癌细胞的PCNA表达,NDCC明显高于DCC,而PCD检测DCC阳性癌细胞高于NDCC.浸润淋巴细胞以T细胞为主.10例中有4例32个腋窝淋巴结发生癌转移,其中20个出现了DCC改变.结论新辅助化疗乳腺癌后残留癌组织DCC变化是反映其疗效的一种形态变化,它可以通过启动细胞凋亡途径使癌细胞坏死以及使细胞增殖能力降低,激发局部组织抗肿瘤的细胞免疫能力,杀死部分淋巴结转移的癌细胞.     

Low-dose aspirin for the prevention of venous thromboembolism in breast cancer patients treated with infusional chemotherapy after insertion of central vein catheter

BACKGROUND: We previously demonstrated a high incidence (7.7%) of venous thromboembolism (VTE) in breast cancer patients treated with infusional chemotherapy after insertion of central vein catheters (CVC). The aim of this study was to evaluate the efficacy and safety of low-dose aspirin for the prevention of VTE. PATIENTS AND METHODS: In a monocentric prospective study, patients with stage II-IV breast cancer, who underwent CVC insertion for continuous infusional chemotherapy, were assigned to receive low-dose aspirin (100 mg daily). Treatment was started after CVC implantation and continued until the last day of chemotherapy. Patients were assessed for safety and for the incidence of symptomatic deep venous thrombosis (DVT) confirmed by color-Doppler ultrasonography. RESULTS: Between April 2000 and March 2004, 188 consecutive patients were included in the study. Median age was 48 years (range 22-83), 31 patients (16%) had concomitant hypertension, and 14 patients (7.4%) were smokers. Median duration of treatment with aspirin was 3.6 months (range 0.4-5.7). A DVT confirmed by color-Doppler ultrasonography was observed in four patients (2.1%; 95% confidence interval, 0.58-5.35%). Side effects included mild epistaxis (three patients, 1.5%) and mild gastric pain (two patients, 1%). No major bleeding complication or International Normal Ratio alteration occurred. CONCLUSIONS: Administration of low-dose aspirin is safe and seems to correlate with a low risk of DVT in breast cancer patients treated with infusional chemotherapy. Further randomized studies comparing low-dose aspirin with other anticoagulative agents are warranted.     

贝伐单抗联合化疗治疗晚期结直肠癌22例临床观察

目的观察贝伐单抗与化疗药物联合治疗晚期结直肠癌的近期疗效和毒副作用。方法在22例经组织或细胞病理学证实的晚期结直肠癌患者中,应用贝伐单抗与化疗药物联合治疗。贝伐单抗的剂量采用美国综合癌症网（NCCN）指南推荐的5mg／kg,每2周重复;或7．5mg／kg,每3周重复。每2个周期后评价疗效并记录毒副作用。结果22例患者中有6例（27．3％）部分缓解,12例（54．5％）稳定,4例（18．2％）进展,客观有效率（ORR）为27．3％,疾病控制率（DCR）为81．8％。毒副作用主要为高血压4例、尿隐血阳性1例、血尿1例,均为1～2级;另出现1例蛋白尿3级,予对症治疗后好转。另外,有3例患者出现III～IV度粒细胞减少,4例出现迟发性腹泻。结论贝伐单抗联合化疗治疗晚期结直肠癌的疗效确切、疾病控制率高、不良反应无明显加重,患者耐受性好。     

NP、MVP与CAP方案治疗晚期非小细胞肺癌的对照研究

目的　比较 3组不同联合化疗方案对晚期非小细胞肺癌的疗效和毒性。方法　统计分析用NP(长春瑞宾、顺铂 )方案、MVP(丝裂霉素、长春地辛、顺铂 )方案及CAP(环磷酰胺、阿霉素、顺铂 )方案治疗的 89例晚期非小细胞肺癌的临床资料。　结果　有效率为 46 .4%( 13/2 8)。MVP组有效率为 40 %( 12 /30 ) ,CAP组有效率为 2 9%( 9/31) ,毒副反应主要为可耐受的骨髓抑制。结论　NP方案及MVP方案均为治疗晚期非小细胞肺癌较为安全有效的化疗方案。     

多西他赛联合卡培他滨治疗晚期乳腺癌疗效分析

目的 研究多西他赛(Docetaxel)联合卡培他滨(Capecitabine/Xeloda)治疗晚期乳腺癌的疗效及可行性.方法 38例晚期乳腺癌患者均给予多西他赛75mg/m2,第1d;希罗达口服2次/d,餐后服用,每次1,000mg/m2,连续服用14d,治疗周期为21d,至少治疗2个周期.结果 该组完全缓解(CR...     

Multicenter phase 2 study of interleukin-2 and 13-cis retinoic acid as maintenance therapy in advanced non-small-cell lung cancer

High serum levels of vascular endothelial growth factor (VEGF) are a poor prognostic factor for patients with advanced non-small-cell lung cancer (NSCLC). We have previously shown that low-dose interleukin (IL)-2 and 13-cis retinoic acid (RA) decreased VEGF and improved the immune function of patients with advanced tumors treated with chemotherapy. The primary end point of this study was to verify whether IL-2 and RA decreased serum VEGF in NSCLC patients showing a clinical benefit from chemotherapy. The secondary end point was the evaluation of clinical outcome. We treated 38 patients with advanced NSCLC who had a complete or partial response or disease stability to chemotherapy and had a median serum VEGF level of 508 ng/mL; as maintenance therapy, they received subcutaneous IL-2 (1.8 x 10(6) IU) and oral RA. Matched controls (n = 87) were selected from a large cohort of patients with a similar disease status, including clinical benefit from chemotherapy. The most common adverse events were mild cutaneous skin rash and fever. Serum VEGF decreased to a mean level of 152 ng/mL (P = 0.0002). A statistically significant improvement in immune function was observed (lymphocyte and natural killer cell numbers and CD4+/CD8+ ratio) with respect to baseline values and controls. An improvement in the clinical outcome was also observed compared with controls. These data show that the administration of low-dose subcutaneous IL-2 and oral RA to patients with advanced NSCLC showing a clinical benefit from chemotherapy is feasible with a low-toxicity profile, decreases VEGF, and seems to improve progression-free and overall survival.