卡培他滨与铂类在晚期乳腺癌一线二线治疗中的疗效对比

目的 分析卡培他滨与铂类在晚期乳腺癌一线、二线治疗中的疗效。方法 2010年1月至2013年6月收治317例晚期乳腺癌患者,采用含卡培他滨或铂类的联合化疗方案,每3周为1周期。采用实体肿瘤疗效评价标准1.1版（RECIST 1.1）评价疗效,不良反应采用NCI CTC 3.0毒性评价标准评价。对采用不同化疗方案的患者进行生存随访并比较其中位无进展生存期（PFS）。结果 一线、二线治疗分别有可评价病例118例和78例。含卡培他滨方案与含铂类方案一线化疗的有效率（53.6% vs. 63.3%）、疾病控制率（81.2% vs. 91.8%）及二线化疗的有效率（42.9% vs. 47.2%）、疾病控制率（90.5% vs. 91.7%）的差异均无统计学意义（P>0.05）;含卡培他滨方案与含铂类方案的一线化疗的中位PFS分别为15.6个月和12.4个月,差异有统计学意义（P<0.05）,二线化疗的中位PFS分别为11.1个月和12.8个月,差异无统计学意义（P>0.05）。不良反应以血液学毒性、恶心呕吐、手足综合症、乏力、口腔溃疡和腹泻为主;与含铂类方案相比,含卡培他滨方案一线化疗的1、2级恶心呕吐发生率较低,手足综合症发生率较高,而二线化疗的1级恶心呕吐、乏力发生率均较低,手足综合症发生率较高,以上差异均有统计学意义（P<0.05）。结论 卡培他滨与铂类均对晚期乳腺癌一线、二线治疗有效,卡培他滨安全耐受性较好,一线治疗的中位PFS更长。     

FUDR为主方案治疗晚期非小细胞肺癌的研究

目的　探讨氟脲脱氧核苷 (floxuridine ,FUDR ,氟苷 )为主方案治疗晚期非小细胞肺癌的疗效和毒性。方法　A组 (观察组 ) 5 0例 ,接受L/FUDR EP方案治疗 ;B组 (对照组 ) 42例 ,接受L/FEP方案治疗。每组均行 3程化疗方评价疗效。结果　A、B两组疗效分别为 40 .0 % (2 0 / 5 0 )及 3 8.1% (16/ 42 ) (P >0 .0 5 )。A组骨髓抑制、消化道反应、脱发、局部静脉炎发生率低于B组 (P <0 .0 1)。结论　FUDR为主方案治疗晚期NSCLC疗效确切 ,毒性较 5 FU低 ,值得临床推广应用。     

肠道支架植入术后卡培他滨联合恩度治疗晚期结肠癌的临床研究

目的  探讨卡培他滨联合重组人血管内皮抑制素（恩度）治疗肠道支架植入术后的晚期结肠癌患者的疗效及安全性。方法  选取2010年1月至2017年1月收治的不能手术切除且伴肠梗阻的晚期结肠癌患者79例,根据其后续治疗方案分为治疗组（39例）和对照组（40例）。所有患者入院后均行肠道支架植入术,解除肠梗阻后,治疗组给予卡培他滨联合恩度治疗,对照组给予卡培他滨单药治疗。治疗周期结束后比较两组的近期疗效和不良反应,并随访两组的无疾病进展生存期和总生存期。结果  所有患者均成功植入肠道支架解除肠梗阻,并完成化疗计划。治疗组患者的总有效率较对照组高,但差异无统计学意义（46.15% vs 30.00%,χ²=2.921,P=0.087）;治疗组疾病控制率亦高于对照组,差异有统计学意义（69.23% vs 50.00%,χ²=3.978,P=0.046）。两组患者化疗及肠道支架植入术相关不良反应发生率相当 （P>0．05）。治疗组中位无疾病进展生存期较对照组延长3个月（16个月 vs 13个月,P＜0.05）,中位总生存期延长6个月（25个月 vs 19个月,P＜0.05）。结论  肠道支架植入术可有效解除结肠癌患者肠梗阻,后续卡培他滨联合恩度治疗的疗效优于卡培他滨单药治疗,且未增加不良反应,患者可耐受。     

UGT1A在伊立替康治疗转移性结直肠癌中的疗效与不良反应预测价值

化疗是转移性结直肠癌（mCRC）的主要治疗手段,伊立替康是mCRC的重要药物,但其存在治疗有效率有限、毒副反应个体差异大的问题。因此需要寻找有效的生物学标志物,筛选出对治疗反应性好、耐受性好的个体以指导临床治疗。尿苷二磷酸葡萄糖醛酸转移酶1A（UGT1A）的基因多态性与伊立替康的毒性及疗效均密切相关,但现有研究结果不一致,预测作用存在争议。本文通过Pubmed检索基因多态性与伊立替康相关性的有关文献,综合分析了UGT1A预测伊立替康毒性局限性的原因,可能与人种差异、药物使用剂量不同及与其他化疗药物或靶向药物联合使用有关。UGT1A多位点基因多态性的检测或与羧酸酯酶（CES）、ATP结合盒子（ABC）转运体、CYP3A4、SCOL等多个基因多态性的联合检测可能是提高伊立替康毒性和疗效预测水平的方式之一。     

The efficacy and relationship between peak concentration and toxicity profile of fixed-dose-rate gemcitabine plus carboplatin in patients with advanced non-small-cell lung cancer

Purpose To investigate the efficacy and relationship between plasma concentrations at the end of infusion (C _{end of infusion}) and toxicity profile of fixed-dose-rate gemcitabine plus carboplatin in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC). Patients and methods Patients were given gemcitabine by 120 min infusion [at a fixed dose rate (FDR) of 10 mg/m²/min] on days 1 and 8 of a 21-day cycle, immediately followed by carboplatin AUC 5 by 4 h infusion on day 1. C _{end of infusion} of gemcitabine was determined by ion-pair reversed-phase high-performance liquid chromatography (HPLC). Results By the close-out date, in our study population, the estimated median time to tumor progression (TTP) was 7 months (95% CI 4–10 months), median overall survival (OS) was 12 months (95% CI 11.2–12.8 months). The mean value of C _{end of infusion} of 21 eligible patients was 16.48 ± 8.07 μmol/l (range 27.43–2.87 μmol/l). The main hematological toxicities were transient grade 3–4 thrombocytopenia. The mean percentages of reduction of WBC, NEC, PLTC and Hb of 21 eligible patients were 38.3 ± 38.1%, 31.3 ± 73.6%, 31.8 ± 53.5% and 12.0 ± 12.2%, respectively. The analysis of the C _{end of infusion} of gemcitabine and the percentage of reduction in WBC showed a significant correlation (r ² = 0.4575; p < 0.05). A significant correlation (r ² = 0.5671; p < 0.05) was also observed between the percentage of reduction of PLTC and C _{end of infusion} of gemcitabine infusion. Conclusion The clinical data in this trial supports the further evaluation the regimen in advanced NSCLC patients, due to its predictable kinetic behavior and less severe toxicity profile than expected.     

吉西他滨联合顺铂治疗晚期膀胱癌的临床观察

目的　评价吉西他滨联合顺铂化疗方案在晚期膀胱癌中的疗效及安全性。方法　３３例接受一线化疗的晚期膀胱癌,予吉西他滨１０００ｍｇ／ｍ^２于第１、８天静脉滴注,顺铂２５ｍｇ／ｍ^２第１～３天静脉滴注,３周重复,每３个月评价客观疗效和毒副反应,并随访无进展生存期（ＰＦＳ）及总生存时间。结果　３３例患者中完全缓解９例,部分缓解７例,有效率为４８.５％;中位无进展生存时间为１１个月,中位生存时间１８个月,１年生存率５８.０％。３～４级白细胞减少９例（２７.３％）,３～４级粒细胞减少６例（１８.２％）,３～４级血小板减少９例（27.３％）,３～４级恶心呕吐６例（１８.２％）。结论　吉西他滨联合顺铂３周方案治疗晚期膀胱癌安全、有效。     

单药泰索帝治疗晚期乳腺癌每周方案与每3周方案疗效及毒性比较

目的：分析单药泰索帝治疗晚期乳腺癌每3周方案与每周方案疗效与毒性的关系。方法：33例晚期乳腺癌患者。其中12例患者接受每3周方案，剂量范围为70．7mg/m^2-86.1mg/m^2，中位剂量为75mg/m^2；20例患者接受每周方案，剂量范围为20．4mg/m^2-28．7mg/m^2，中位剂量为25mg/m^2。结果：本组患者的总有效率为25．0％，其中软组织、肺、骨及肝脏有效率分别为60％、23．1％、21．4％和27．8％；既往应用过蒽环类的患者有效率为25．0％，既往应用过紫杉醇的患者有效率27．3％；每3周方案与每周方案疗效均为25．0％，两者之间无统计学差异；每3周方案的Ⅲ度～Ⅳ度白细胞毒性大．而每周方案白细胞毒性轻，耐受性良好。结论：单药泰索帝治疗晚期乳腺癌疗效肯定。对老年、一般状况差及部分难治性乳腺癌患者仍有疗效，每周方案更易被耐受。     

多西紫杉醇联合卡培他滨治疗转移性乳腺癌的临床研究

背景与目的:对于既往使用过含蒽环、紫杉醇药物方案化疗失败的复发转移性乳腺癌,可用的药物不多.多西紫杉醇(docetaxel)联合卡培他滨(capecitabine)是近年来治疗转移性乳腺癌一个较新的方案,本研究初步探讨多西紫杉醇联合卡培他滨(DC)治疗转移性乳腺癌的近期疗效和安全性情况.方法:31例女性转移性乳腺癌患者接受多西紫杉醇联合卡培他滨方案化疗.卡培他滨2 500 mg·(m2·d)-1,第1～14天,分2次饭后30 min口服;多西紫杉醇75 mg/m2静滴1 h,第1天.方案21天重复循环.在多西紫杉醇用药前1天,开始口服地塞米松8 mg,每天2次,连用3天.结果:31例患者使用DC方案化疗共116疗程,中位疗程数为3.7个.总有效率(response rate,RR)为41.9%(13/31),完全缓解(complete remission,CR)3例(9.6%).主要不良反应为乏力、骨髓抑制、胃肠道反应、手足综合征、粘膜炎等.中位随访时间10.8个月(2～23个月),死亡2例(均死于肿瘤进展),中位无进展生存期(progression-free survival,PFS)5.7个月(2～12个月).结论:多西紫杉醇与卡培他滨联合治疗转移性乳腺癌,有效率高、疗效肯定、不良反应可以耐受,为治疗转移性乳腺癌的有效方案.     

Early severe toxicities after capecitabine intake: possible implication of a cytidine deaminase extensive metabolizer profile

We report here the case of a 19-year-old female patient who suffered from extremely severe toxicities (G4 mucitis, fever, diarrhea, alteration of general state) while undergoing low-dose capecitabine treatment for her metastatic corticosurrenaloma. The severe toxicities stopped as soon as treatment was suspended. Interestingly, this patient was not deficient in DPD, a pharmacogenetic syndrome usually associated with increased risk of developing severe/lethal toxicities in patients undergoing fluoropyrimidine therapy, and she had been treated previously with 5-FU with a good tolerance. We then hypothesized that cytidine deaminase (CDA) extensive phenotype could be responsible for the severe toxicities observed with capecitabine. CDA is affected by genetic polymorphism, with subsequent acquisition of either deficient or extensive metabolizer profile. Phenotypic investigations confirmed that CDA activity in this patient was +180% higher than the ones usually recorded in the general population. This strongly suggests that the extensive activation of triple-prodrug capecitabine could have occurred in this patient, resulting in overexposure to 5-FU and its cytotoxic metabolites eventually. This case report suggest for the first time that severe toxicities with a capecitabine-containing protocol could be, at least in part, linked with an extensive-CDA syndrome. The case reported here suggests therefore that besides DPD, screening for CDA activity could be of interest to ensure a better safety in the handling of oral capecitabine at the bedside.     

培美曲塞联合卡培他滨治疗晚期乳腺癌的疗效观察

目的观察培美曲塞联合卡培他滨治疗晚期乳腺癌的临床疗效和不良反应。方法培美曲塞500mg/m2,第1天;卡培他滨2500mg/（m2·d）,分2次口服,第1～14天,21d为1个周期。所有病例均接受至少2个周期的化疗。结果 27例患者入组均可评价疗效,CR率3.7%（1/27）,PR率22.2%（6/27）,SD率37.0%（10/27）,PD率37.0%（10/27）,有效率25.9%（7/27）,临床获益率55.6%（15/27）。中位随访期10个月,中位TTP7个月,中位OS9.5个月,1年生存率为66.7%。主要不良反应为骨髓毒性及手足综合征,Ⅲ度及Ⅳ度白细胞减少为18.5%（5/27）。手足综合征发生率77.7%（21/27）,其中,Ⅲ度及Ⅳ度手足综合征发生率为7.4%（2/27）。结论培美曲塞联合卡培他滨方案治疗蒽环类和紫杉类耐药转移性乳腺癌有较好的疗效,患者耐受性好,值得临床进一步研究。     

希罗达治疗转移性乳腺癌的疗效和安全性的临床研究

目的：评价希罗达(Xeloda)治疗国人转移性乳腺癌的疗效及其安全性。方法：2001年6月至2002年8月，共入选76例转移性乳腺癌病人。所有病人均予希罗达2500mg／m^2／天，分早晚两次，饭后30分钟内口服，连服14天，间歇7天，即每个治疗周期为2l天；至少治疗2周期。结果：76例中，l例完全缓解，25例部分缓解。病情稳定34例(44．7％)，疾病进展为15例(19.7％)。总有效率为34.2％。肿瘤控制率(CR PR SD)为78．9％。毒性反应Ⅰ／Ⅱ级主要为手足综合征19例(25．0％)、恶心13例(17．1％)和腹泻12例(15．8％)；Ⅲ级主要为恶心2例(2．6％)、呕吐2例(2．6％)、血小板减少2例(2．6％)、GOT升高2例(2．6％)及头晕l例(1．3％)，无Ⅳ级毒性。结论：口服希罗达治疗国人复治的转移性乳腺癌疗效较高，耐受性好，可以失言应用。     

Efficacy and safety of low-dose metronomic chemotherapy with capecitabine in heavily pretreated patients with metastatic breast cancer

Aim

Registered dose capecitabine monotherapy is active against metastatic breast cancer (MBC), but retrospective analyses indicate that lower doses may be as effective and better tolerated. This study was conducted to assess the safety and efficacy of metronomic capecitabine in heavily pretreated patients with MBC.

Patients and methods

In this phase II study 60 MBC patients received continuous metronomic capecitabine monotherapy (1500 mg once a day). Primary endpoint was clinical benefit rate, secondary end points were clinical benefit rates (CBRs), tumour response rates (RRs), overall survival (OS), time to progression (TTP), duration of response (DOR) and toxicity.

Results

Fifty eight assessable patients received two or more 28-day cycles of metronomic capecitabine. The CBR was 62%. Median DOR was 7 months. Median TTP and OS were 7 and 17 months, respectively. Two partial responses and 7 cases of stable disease were recorded in 13 patients who had previously received capecitabine intermittently (2000 mg/m²/day on days 1-14 every 21 days) as first- or subsequent-line treatment for MBC. Grade 3-4 adverse events were uncommon; haematologic toxicity was infrequent (5%) and consistently mild.

Conclusion

This regimen of metronomic capecitabine displayed good activity and excellent tolerability in MBC patients, including those who had previously received the drug at standard doses.     

奥沙利铂联合卡培他滨一线治疗结直肠癌根治术后复发患者的分类及回归树分析

目的 探讨奥沙利铂（L-OHP）联合卡培他滨（CAP）一线治疗转移性结直肠癌（mCRC）临床疗效的预测因素及其相关性。方法 2006年3月至2010年12月共80例mCRC患者采用L-OHP联合CAP方案一线治疗,具体为：L-OHP 130mg／m2静滴2h,d1;CAP 2000mg／m2 分2次口服,d2～d15,21天为1周期。采用分类及回归树（CART）分析该方案的客观疗效和无进展生存时间（PFS）的预测因素。结果 80例mCRC患者共完成化疗368个周期,平均4.6个周期。全组均可评价疗效,获CR 12例,PR 25例,SD 27例,PD 16例,有效率（RR）为46.2％,中位PFS为9.6个月（95％CI：8.2～11.0个月）。客观疗效的CART分析将组织分化情况作为第一级划分位点,术后肝转移和无瘤间期作为次级划分位点,逐级获得4个终末亚组,其中高、中分化且无瘤间期＞12个月组的RR最高,为77.8％,低、未分化且肝转移组最低,仅为8.0％。 PFS的CART分析将客观疗效作为第一级划分位点,术后肝转移作为次级划分位点,逐级获得3个终末亚组,其中获有效组的PFS均数最大,为11.1个月,未获有效且术后肝转移组最小,仅为80个月;经Log-rank检验显示,获有效组的中位PFS优于其他两组（P＜0.05）。结论 L-OHP联合CAP一线治疗mCRC的客观疗效可能与患者术后是否肝转移和无瘤间期长短有关,其PFS则与客观疗效和术后肝转移关系密切,精确的临床疗效关联预测值得深入探讨。     

DX方案与XELOX方案一线治疗晚期胃癌疗效比较

目的 观察DX方案（多西紫杉醇联合卡培他滨）与XELOX方案（草酸铂联合卡培他滨）治疗晚期胃癌的客观疗效和毒性反应。方法DX方案组21例晚期胃癌患者接受多西紫杉醇75mg／m^2d1卡培他滨每日1700mg／m^2,分2次口服,dl—14,21d为1周期,疗程2—6周期。XELOX方案组20例晚期胃癌患者接受奥沙利铂130mg／m^2dl,卡培他滨每日1700mg／m^2,分2次口服,dl—d14,21d为1周期,疗程2—6周期。结果DX方案组总有效率为52．4％常见的毒性反应为中性粒细胞减少性发热、脱发、腹泻及口腔黏膜炎发生率较高;XELOX方案组总有效率为50．0％,常见的毒性反应为手足综合征和周围神经毒性反应等。结论DX方案和XELOX方案均为治疗进展期胃癌较好的方案,其中XELOX方案副反应较低可提高患者的生存质量,毒副作用能耐受,更适合老年体弱病人。     

The efficacy of lapatinib and capecitabine in HER-2 positive breast cancer with brain metastases: A systematic review and pooled analysis

IntroductionBreast cancer (BC) with HER-2/neu overexpression or amplification (HER-2+) is associated with a higher prevalence of brain metastases (BMs) when compared to other subtypes. Among approved drugs for HER-2+ BC, lapatinib (L) is associated with single agent activity toward BMs. We conducted a systematic review to determine the efficacy of L, singly or in combination with capecitabine (C), as a treatment for HER-2+ BMs.Material and methodsWe searched PubMed, EMBASE, The Cochrane Library, SCOPUS, Web of Science, ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform (ICTRP), and the European Union Clinical Trials Register for studies reporting data on L, singly or in combination with C, for the treatment of HER-2+ BC with BMs. Primary end-points were overall response rate (ORR) and disease control rate (DCR); these were pooled to provide an aggregate value. Progression-free survival (PFS) and overall survival (OS) were secondary end-points. Data were pooled using number of events/number of evaluable patients, according to a fixed or random effect model.ResultsOverall, 12 studies were included in the present meta-analysis, for a total of 799 patients with BMs. The pooled overall response rate (ORR) was 21.4% (95% CI 11.7–35.9). After exclusion of patients that received L alone, ORR reached 29.2% (95% CI 18.5–42.7). The pooled median PFS and OS were 4.1 (95% CI 3.1–6.7) and 11.2 (95% CI 8.9–14.1) months, respectively.ConclusionsDue to its activity on BMs, the L + C combination may be considered for HER-2+ BC that has progressed in the brain, when local therapy has been performed or failed and re-irradiation is not feasible.     

Predictive factors for efficacy of capecitabine in heavily pretreated patients with metastatic breast cancer

Purpose  The purpose of the present study is to evaluate what clinical factors affect the efficacy, time to treatment failure (TTF), and overall survival (OS) of oral capecitabine monotherapy in heavily pretreated patients with metastatic breast cancer (MBC). Methods  A total of 102 consecutive patients with MBC who had been administered capecitabine monotherapy between June 2003 and August 2004 were retrospectively reviewed. Capecitabine (828 mg/m²) was given twice daily for 3 weeks followed by a 1-week rest period; this was repeated every 4 weeks. We evaluated the potential clinical factors for TTF and OS, using univariate analysis (log-rank test) and the multivariate Cox regression model. Median follow-up was 16.9 months. Results  A total of 100 patients (98%) had been pretreated with either anthracyclines or taxanes, and 81 patients (79%) with both anthracyclines and taxanes. Response rate was 17% and clinical benefit rate was 41%. Median TTF and OS were 4.9 and 24.3 months, respectively. Multivariate analysis demonstrated that no liver metastasis (P = 0.015), good performance status (P = 0.033), longer disease-free interval (P = 0.036), and hormone receptor-positive tumor (P = 0.038) were significant for TTF. No liver metastasis (P = 0.00012), objective response to capecitabine (P = 0.00084), and good performance status (P = 0.0011) were significant for OS. Conclusions  Capecitabine monotherapy is effective over the long term for heavily pretreated patients with MBC who have no liver metastasis, good performance status, longer disease-free interval, or hormone receptor-positive tumor. Patients who have no liver metastasis, who respond to capecitabine, or who have good performance status are expected to survive even longer.     

Renal function,body surface area,and age are associated with risk of early-onset fluoropyrimidine-associated toxicity in patients treated with capecitabine-based anticancer regimens in daily clinical care

BackgroundThe objective of this analysis was to determine the factors associated with early onset treatment-related toxicity in patients treated with capecitabine-based anticancer regimens in daily clinical care.Patients and MethodsA total of 1463 patients previously included in a prospective cohort study and treated with standard-of-care capecitabine-based anticancer regimens (monotherapy or combined with other chemotherapy or radiotherapy) were analysed. Logistic regression models were developed to investigate associations between patient- and treatment-related factors and occurrence of early – i.e. cycle one or two – severe (grade ≥ 3) treatment-related toxicity, toxicity-related hospitalisation, and toxicity-related treatment discontinuation. Performance of models was evaluated using receiver-operating characteristic (ROC) curves and internal validity was explored using bootstrap analysis.ResultsAmong 1463 patients included, 231 patients (16%) experienced early severe toxicity, 132 patients (9%) were hospitalised for toxicity, and 146 patients (10%) discontinued treatment for toxicity; in total, 321 patients (22%) experienced any early toxicity-related adverse outcome. Predictors of early grade ≥3 toxicity, after adjustment for treatment regimen, were renal function (odds ratio [OR] 0.85 per 10 ml/min/1.73 m², p = 0.0007), body surface area (BSA) (OR 0.33 per m², p = 0.0053), age (OR 1.14 per decade, p = 0.0891), and elevated pre-treatment uracil concentrations (OR 2.41 per 10 ng/ml, p = 0.0046). Age was significantly associated with fatal treatment-related toxicity (OR 5.75, p = 0.0008). Area under the ROC curve (AUC) of a model to predict early grade ≥3 toxicity was 0.704 (95% confidence interval 0.666–0.743, optimism-corrected AUC 0.690).ConclusionRenal function, BSA, and age, in addition to pre-treatment uracil, are associated with clinically relevant differences in risk of early severe toxicity in patients treated with capecitabine in routine clinical care.     

Evaluation of the efficacy and toxicity of upper extremity isolated limb infusion chemotherapy for melanoma: An Australian multi-center study

BackgroundIsolated limb infusion (ILI) is a minimally invasive treatment for patients with locally advanced extremity melanoma. Most studies combine results of upper-limb ILI (UL-ILI) and lower-limb ILI (LL-ILI), leaving UL-ILIs relatively underreported as LL-ILIs comprise the vast majority in these reports. However, differences between the two procedures may be clinically important. The aim of this study was to evaluate the efficacy and toxicity of UL-ILI in an Australian multi-center setting.Patients and methods316 ILI procedures for melanoma performed between 1992 and 2008 in five Australian institutions were analyzed. In all institutions melphalan (±actinomycin D) was circulated in the isolated limb for 20–30 min.ResultsBaseline patient characteristics for UL-ILI (n = 27) and LL-ILI (n = 289) were similar, except that more men underwent UL-ILI (66% vs. 38%; p = 0.007) and disease in LL-ILI was mostly located on the distal limb (p = 0.02). Median tourniquet times were shorter for UL-ILI (38 vs. 48 min; p = 0.04) and UL-ILI patients experienced less limb toxicity (Grade III/IV in 24% vs. 31%; p = 0.01). Complete response (CR) rates were similar: 33% after LL-ILI (p = 0.70), 30% after UL-ILI, while overall response (OR) rates were higher after LL-ILI: (76%) than UL-ILI (59%; p = 0.05). No difference in survival was seen.ConclusionsUL-ILI is safe to perform and effective, resulting in low limb toxicity. CR rates were similar to those for LL-ILI, but OR rates were lower for UL-ILI. It may be possible to improve OR rates achieved by UL-ILI by optimizing perioperative factors, while maintaining low toxicity.     

Trends in the characteristics,dose-limiting toxicities and efficacy of phase I oncology trials: The Cancer Research UK experience

IntroductionPhase I oncology trials have evolved over the years, and these changes could have implications for future studies and patients.MethodsAdult trials sponsored by Cancer Research UK Centre for Drug Development between 1995 and 2013 were analysed. Forty-nine trials were divided into two groups based on the starting date for recruitment: 1995–2003 (24 trials, n = 603) and 2004–2013 (25 trials, n = 750) for comparative purposes.ResultsFrom 1995–2003 to 2004–2013, there was a shift towards studying non-cytotoxic agents that are administered orally. In later trials, patients tended to have better performance status, were older, had greater disease burden, and were more likely to have received prior treatment. In 2004–2013, wider variety of dose escalation designs were used, and studies were more likely to be multicentre, target/disease specific, conducted in first-/any-line setting and to require tumour biopsy. The overall incidence of dose-limiting toxicities (DLTs) was unchanged (10.9%; risk of death 0.4%), but DLTs such as neuropathy, stomatitis and thrombocytopaenia were less frequent in the more recent trials, while elevated liver enzymes were more frequent. Non-classical DLTs emerged in the later trials, including hypertension, hypophosphataemia, cardiac and ophthalmic toxicities. Disease control rate (DCR) increased from 27.9% (1995–2003) to 36.0% (2004–2013; P = 0.0033) due to higher rates of disease stabilisation.ConclusionChanges in trial designs, therapeutic agents, patient characteristics and DLTs were observed. Although the nature of DLTs changed, the incidence was similar in the two time periods and DCR improved, suggesting that the benefit-risk balance for patients participating in early-phase trials remains acceptable.     

晚期胃癌一线XELOX方案化疗后卡培他滨维持治疗的临床观察

目的 探讨晚期胃癌一线奥沙利铂联合卡培他滨（XELOX方案）化疗后卡培他滨维持治疗的疗效和安全性。方法 84例晚期胃癌经一线XELOX方案化疗有效后分为治疗组与对照组,每组42例;治疗组采用卡培他滨维持化疗至疾病进展或出现不可耐受的不良反应,对照组随访观察。结果 治疗组中位无进展生存时间（progression free survival,PFS）为9.6个月,对照组为6.8个月（P<0.05）;治疗组中位总生存时间（overall survival,OS）为13.5个月,对照组为11.6个月（P<0.05）。主要不良反应有血液学毒性、胃肠道反应、手足综合征、口腔黏膜炎、周围神经毒性等,经对症治疗后均好转,无治疗相关性死亡。结论 晚期胃癌一线XELOX方案化疗有效后卡培他滨维持治疗可延长PFS及OS,不良反应可耐受。