节拍化疗模式下卡培他滨强化依西美坦抑制乳腺癌MCF-7细胞增殖的实验研究

目的:研究节拍化疗模式下卡培他滨联合依西美坦对乳腺癌MCF-7细胞的增殖抑制作用及信号通路机制。方法:实验分为7组,CCK-8法检测单药与联合用药组对MCF-7细胞增殖的抑制率。流式细胞仪检测分析药物作用对MCF-7细胞周期与细胞凋亡的影响。Western blot法检测各用药组MCF-7细胞p27、Bcl-2、PI3K和AKT蛋白的表达情况。结果:卡培他滨的半数抑制浓度（half maximal inhibitory concentration,IC50)为282.7 μmol/L、依西美坦IC50为103.5 μmol/L;联合用药组对MCF-7细胞增殖的抑制率高于单药组（P=0.003）;联合用药组中减小卡培他滨剂量不会显著降低细胞增殖抑制率（P=0.916）;与单药组影响细胞周期不同,联合用药会使MCF-7细胞停滞于S期或G1期;Western blot检测显示,联合用药会促进p27表达,抑制PI3K表达,促使细胞凋亡;低剂量卡培他滨会显著抑制Bcl-2表达（P=0.006）,使细胞停滞于S期。结论:小剂量卡培他滨节拍化疗联合依西美坦通过不同模式多方位影响MCF-7细胞周期及信号因子表达,显著抑制MCF-7细胞增殖。     

泰索帝联合希罗达治疗蒽环类化疗失败复发转移性乳腺癌的临床研究

目的研究泰索帝联合希罗达治疗蒽环类药物治疗失败复发转移性乳腺癌的疗效和安全性.方法 18例蒽环类药物治疗失败的复发转移性乳腺癌患者均接受泰索帝联合希罗达方案治疗,随机分为A组:泰索帝75mg/m2静滴,第1天;希罗达950mg/m2口服,每日2次,第1～14天,每3周为1周期;B组:泰索帝37.5mg/m2静滴第1、8天;希罗达950mg/m2口服,每日2次,第1～14天,每3周为1周期.每周期评价疗效同时记录不良事件.结果 18例患者均可评价疗效,完全缓解(CR)无,部分缓解(PR)13例,有效率(CR PR)72%(13/18).A组有效率88.9%(8/9),B组有效率55.6%(5/9).两组共56周期可评价毒性反应,无严重不良事件导致死亡的患者,中性粒细胞减少是主要不良反应,Ⅲ～Ⅳ度占58.9%,A组Ⅳ度中性粒细胞减少30.9%,B组3.7%(P=0.012).结论泰索帝联合希罗达是治疗蒽环类药物治疗失败复发转移性乳腺癌的有效方案,其不良反应能够耐受.     

健脾祛瘀方联合卡培他滨、伊立替康治疗晚期大肠癌20例

[目的]观察健脾祛瘀方联合卡培他滨、伊立替康治疗晚期大肠癌疗效。[方法]将40例随机分为两组。对照组20例采用卡培他滨(Xeloda)+伊立替康(CPT-11)方案;治疗组采用健脾祛瘀方联合化疗。观察CEA值、Karnofsky评分、生活质量评分及血常规、肝肾功能等安全性指标,治疗两个月进行疗效判定。[结果]健脾祛瘀方联合化疗治疗晚期大肠癌,在降低CEA值、改善体力状况、提高患者生活质量等方面优于单纯化疗。[结论]中西医结合治疗晚期大肠癌可提高疗效减轻副作用。     

TX方案治疗铂类治疗失败的进展期胃癌的临床疗效分析

目的：评价紫杉醇联合卡培他滨作为含铂类药物治疗失败的进展期胃癌二线治疗的疗效及安全性。方法：既往接受FP或者FOLFOX4方案化疗的进展期胃癌患者36例,采用TX方案化疗,紫杉醇145mg/m2静脉滴注3h,d1;卡培他滨2000mg/m2,分2次口服,d1-14,21天为一个周期,随访观察疗效,不良反应,进展时间和生存期。结果：36例患者共接受142个周期的化疗,中位化疗周期数4个。全组36例患者中有35例可评价疗效及不良反应,其中8例部分缓解,有效率为22.8%（95%CI：8.2%-37.5%）。中位进展时间和生存时间分别为4.8个月（95%CI：2.9-6.2）和8.1个月（95%CI：6.4-12.7）。Ⅲ/Ⅳ度不良反应主要为骨髓抑制、手足综合征及脱发。结论：紫杉醇联合卡培他滨方案二线治疗进展期胃癌疗效确切,不良反应小,尤其对老年患者耐受性好。     

NCb与NX方案治疗蒽环及紫杉类耐药的乳腺癌的临床研究

目的:观察长春瑞滨联合卡铂与长春瑞滨联合卡培他滨(Xeloda)对紫杉类及蒽环类耐药的晚期乳腺癌的疗效及不良反应。方法:80例确诊为紫杉类、蒽环类耐药的晚期乳腺癌患者随机分为A、B两组,各40例,A组:长春瑞滨25mg/m2,静滴,d1、8,卡培他滨1650mg/m2,口服,d1-14;B组:长春瑞滨25mg/m2,静滴,d1、5,卡铂350mg/m2,静滴,d1;3周1个周期,平均4周期,化疗结束2-3周后评价疗效。结果:78例患者可评价疗效,A组有效率37.5%,1年生存率42.5%,中位进展时间4.6个月;B组有效率42.1%,1年生存率45%,中位进展时间3.4个月,两组各指标差异无显著性(P>0.05)。A组患者的手足综合症发生率明显高于B组(P<0.05);B组患者的呕吐、白细胞及血小板减少发生率明显高于A组(P<0.05),但Ⅲ-Ⅳ度呕吐、白细胞及血小板减少的发生率无明显升高(P>0.05)。结论:对于紫杉类、蒽环类耐药的晚期乳腺癌患者,长春瑞滨联合卡铂是一个安全、有效、经济的化疗方案。     

Correlation of capecitabine-induced skin toxicity with treatment efficacy in patients with metastatic colorectal cancer: results from the German AIO KRK-0104 trial

Background:

The AIO KRK-0104 randomised phase II trial investigated the efficacy and safety of two capecitabine-based regimens: combination of capecitabine and irinotecan (CAPIRI) plus cetuximab (CAPIRI-C) and combination of capecitabine with oxaliplatin (CAPOX) plus cetuximab (CAPOX-C) in the first-line treatment of metastatic colorectal cancer (mCRC). Treatment-related skin toxicity (ST) was evaluated separately for capecitabine and cetuximab. The present analysis investigates the correlation of capecitabine-attributed ST (Cape-ST) and parameters of treatment efficacy.

Methods:

Patients with mCRC were randomised to cetuximab (400 mg m⁻², day 1, followed by 250 mg m⁻² weekly) plus CAPIRI (irinotecan 200 mg m⁻², day 1; capecitabine 800 mg m⁻², twice daily, days 1–14, every 3 weeks), or cetuximab plus CAPOX (oxaliplatin 130 mg m⁻², day 1; capecitabine 1000 mg m⁻², twice daily, days 1–14, every 3 weeks).

Results:

Of 185 recruited patients, 149 (CAPIRI-C, n=78; CAPOX-C, n=71) received study treatment beyond the first tumour assessment and were evaluable for efficacy. Capecitabine-attributed ST, predominantly hand–foot syndrome, was observed in 32.2% of patients. Capecitabine-attributed ST grade 1–3 was associated with a significantly higher disease control rate (DCR) (97.9 vs 86.1%, P=0.038) compared with grade 0 toxicity. Moreover, Cape-ST grade 1–3 related to a markedly longer progression-free survival (PFS) (9.9 vs 5.6 months, P<0.001) and overall survival (OS) (32.8 vs 22.4 months, P=0.008). Separate analyses of treatment arms indicated that the effect of Cape-ST on PFS remained significant for both arms, whereas the effect on OS remained apparent as a strong trend.

Conclusion:

This analysis supports the hypothesis that for the evaluated regimens, a correlation exists between Cape-ST and treatment efficacy regarding DCR, PFS, and OS.     

XELOX vs FOLFOX-4 as first-line therapy for metastatic colorectal cancer: NO16966 updated results

Background:

We report updated overall survival (OS) data from study NO16966, which compared capecitabine plus oxaliplatin (XELOX) vs 5-fluorouracil/folinic acid plus oxaliplatin (FOLFOX4) as first-line therapy in metastatic colorectal cancer.

Methods:

NO16966 was a randomised, two-arm, non-inferiority, phase III comparison of XELOX vs FOLFOX4, which was subsequently amended to a 2 × 2 factorial design with further randomisation to bevacizumab or placebo. A planned follow-up exploratory analysis of OS was performed.

Results:

The intent-to-treat (ITT) population comprised 2034 patients (two-arm portion, n=634; 2 × 2 factorial portion, n=1400). For the whole NO16966 study population, median OS was 19.8 months in the pooled XELOX/XELOX-placebo/XELOX-bevacizumab arms vs 19.5 months in the pooled FOLFOX4/FOLFOX4-placebo/FOLFOX4-bevacizumab arms (hazard ratio 0.95 (97.5% CI 0.85–1.06)). In the pooled XELOX/XELOX-placebo arms, median OS was 19.0 vs 18.9 months in the pooled FOLFOX4/FOLFOX4-placebo arms (hazard ratio 0.95 (97.5% CI 0.83–1.09)). FOLFOX4 was associated with more grade 3/4 neutropenia/granulocytopenia and febrile neutropenia than XELOX, and XELOX with more grade 3 diarrhoea and grade 3 hand-foot syndrome than FOLFOX4.

Conclusion:

Updated survival data from study NO16966 show that XELOX is similar to FOLFOX4, confirming the primary analysis of progression-free survival. XELOX can be considered as a routine first-line treatment option for patients with metastatic colorectal cancer.     

伊立替康联合卡培他滨治疗晚期胃癌疗效分析

目的 观察伊立替康联合卡培他滨治疗晚期胃癌的疗效和毒副反应.方法 全组24例胃癌均接受化疔.具体方案:伊立替康180 mg/m<'2>,静脉滴注,d<,1>;卡培他滨1 650 mg/(m<'2>·d),口服,d<,1～5>.14 d为1个周期,4个周期后评价疗效和毒副反应.结果 全组24例中,CR 1例,PR 8例,...     

Bosutinib plus capecitabine for selected advanced solid tumours: results of a phase 1 dose-escalation study

Background:

This phase 1 study evaluated the maximum tolerated dose (MTD), safety, and efficacy of bosutinib (competitive Src/Abl tyrosine kinase inhibitor) plus capecitabine.

Methods:

Patients with locally advanced/metastatic breast, pancreatic, or colorectal cancers; cholangiocarcinoma; or glioblastoma received bosutinib plus capecitabine at eight of nine possible dose combinations using an ‘up-down'' design to determine the toxicity contour of the combination.

Results:

Among 32 enrolled patients, none of the 9 patients receiving MTD (bosutinib 300 mg once daily plus capecitabine 1000 mg m⁻² twice daily) experienced dose-limiting toxicities (DLTs). Overall, 2 out of 31 (6%) evaluable patients experienced DLTs (grade 3 neurologic pain (n=1); grade 3 pruritus/rash and increased alanine aminotransferase (n=1)). Most common treatment-related adverse events (AEs) were diarrhoea, nausea, vomiting, palmar-plantar erythrodysesthesia (PPE), fatigue; most frequent grade 3/4 AEs: PPE, fatigue, and increased alanine/aspartate aminotransferase. Although diarrhoea was common, 91% of affected patients experienced maximum grade 1/2 events that resolved. Best overall confirmed partial response or stable disease >24 weeks (all tumour types) was observed in 6 and 13% of patients.

Conclusions:

In this population of patients with advanced solid tumours, bosutinib plus capecitabine demonstrated a safety profile similar to that previously reported for bosutinib or capecitabine monotherapy; limited efficacy was observed.