重组人血管内皮抑制素联合化疗治疗转移性结直肠癌的临床观察

目的 观察重组人血管内皮抑制素（恩度）与化疗联合治疗晚期结直肠癌的有效性和安全性。方法 自2006年8月至2009年5 月,5 例初治转移性结直肠癌患者和18 例复治转移性结直肠癌患者接受恩度联合细胞毒药物治疗。恩度15mg/d,加人生理盐水500ml 静脉滴注,连用14 天。同时8 例患者采用FOLFIRI 方案化疗,2 例患者采用CAPIRI 方案化疗,9 例患者采用GLF 方案化疗,4 例患者采用FOLFOX4 或XELOX 方案化疗。分别按照RECIST 1.0 和NCI-CTC 3.0 评价疗效和毒性。结果23 例可评价毒性,21 例可评价疗效。在4 例初治患者中,2 例SD, 2 例PD。在17 例复治患者中,8 例SD, 9 例PD,疾病控制率（DCR）为47.1％。全组中位肿瘤进展时间（mTTP）为5 个月（95 % CI: 2.2～7.8 个月）,中位总生存时间(mOS）为12 个月（95% CI: 10.5～13.5 个月）。复治患者的mTTP 和mOS 分别为4 个月（95% CI: 1.7～6.3 个月）和11.5 个月(95 %CI: 8.5～14.5 个月）。主要不良反应为血液学毒性、恶心呕吐,考虑主要与化疗相关。轻度心血管系统毒性考虑与恩度相关。结论恩度联合细胞毒药物治疗转移性结直肠癌安全性好,恩度未增加化疗药物的毒性。对复治患者有延长疾病控制时间的趋势,值得进一步研究。     

重组人血管内皮抑素联合化疗一线治疗转移性结直肠癌的临床观察

目的　探讨重组人血管内皮抑素（恩度）联合化疗一线治疗转移性结直肠癌的安全性与疗效。方法　１６例转移性结直肠癌患者,在常规化疗基础上联合恩度进行一线治疗,化疗方案包括ＸＥＬＯＸ方案、ＸＥＬＩＲＩ方案和卡培他滨单药,恩度１５ｍｇ／天静滴,第１～１４天。３周为１周期,共进行４～６个周期。结果　１６例患者共完成８３个周期的治疗,平均５.２个周期,均可评价不良反应和客观疗效。主要不良反应为骨髓抑制、胃肠道反应、神经毒性和手足综合征,多为１～２级,且与化疗相关。疗效评价获ＰＲ６例,ＳＤ７例,ＰＤ３例,客观缓解率为３７.５％,疾病控制率为８１.３％;中位无进展生存期为９.２０个月（９５％ＣＩ：３.３９～１５０１）,中位生存期为１５.３个月（９５％ ＣＩ：６.１８～２４.４２）;与治疗前相比,治疗后ＣＥＡ（Ｐ＝０.０４９）和ＣＡ１９９（Ｐ＝０.０４８）均显著下降。结论　恩度联合化疗一线治疗转移性结直肠癌安全有效。     

Impact of chemotherapy beyond the first line in patients with metastatic breast cancer

Purpose The goal of this study was to determine which benefit could be brought by the succession of chemotherapy lines in patients treated for metastatic breast cancer and to identify patients who benefit from these treatments. Patients and methods Nine hundred and thirty four patients with metastatic breast cancer diagnosed between 1992 and 2002 were studied. A total of 772, 505, 283, 127 and 55 patients received a first, second, third, fourth and fifth line of chemotherapy, respectively. The evaluation of benefit in each chemotherapy lines was based on time of disease control (TDC). TDC is defined as time between the date of the beginning of treatment and the date of progression of disease or death. In case of early progressive disease or progression diagnosed at the first evaluation, TDC value is zero. Cox proportional hazards model was used to identify factors that could influence the TDC in each line of chemotherapy. Results Medians duration of TDC are 9.3 [0–120], 5.9 [0–83.6], 4.63 [0–37.2], 4.1 [0–36.7] and 0.23 months [0–15] in first, second, third, fourth and fifth lines, respectively. More interestingly, TDC was longer than 6 months in 50.5% of patients treated with second line, 40% with third line, 35% with fourth line and 23.5% with fifth line. These results justify the therapeutic succession of chemotherapy lines in metastatic breast cancer. Only one factor influences the duration of TDC for each line of treatment: duration of TDC observed in the previous line.     

Mortality of patients with metastatic colorectal cancer who received elective or emergent operation after exposure to bevacizumab: A nationwide database study

IntroductionTreatment guidelines for colorectal cancer (CRC) indicate that surgical intervention within 4 weeks or 8 weeks after bevacizumab therapy might increase the risk of postoperative complications and mortality, especially in patients who received emergent operation. Therefore, we aimed to assess the association between different surgical timings, emergent or elective surgery, and the risk of postoperative mortality.Materials and methodsUsing the Taiwan National Health Insurance Database and Taiwan Cancer Registry, we identified patients with metastatic colorectal cancer (mCRC) who underwent surgery within 1 year of receiving bevacizumab between January 2010 and December 2017. The primary outcomes were 30-day, 60-day, and in-hospital mortality; the secondary outcomes were hospital stay, 30-day readmission rate, and surgical complications. Multivariate analysis was used to adjust for confounders.ResultsThis study included 2,047 patients. In the multivariate analysis, patients who underwent emergent operation and had higher Charlson scores had a significantly higher mortality rate. Patients with a longer interval to surgery, more cycles of bevacizumab treatment, and distal metastectomy had the opposite result. In subgroup analysis, patients who received emergent operation within 28 days had the highest surgical mortality.ConclusionsThe interval to operation among mCRC patients who receive bevacizumab treatment should exceed 4 weeks to avoid additional risk of mortality whether patients receiving elective or emergent operation. Patients who received emergent operation within 28 days of bevcizumab infusion had the highest risk of mortality.     

Combination chemotherapy of biweekly irinotecan (CPT-11) plus tegafur/uracil (UFT) and leucovorin (LV) for patients with metastatic colorectal cancer: phase I/II study in Japanese patients

Purpose  We aimed to evaluate the safety and efficacy of combination chemotherapy with biweekly irinotecan (CPT-11) plus oral tegafur/uracil (UFT) and leucovorin (LV) in patients with previously untreated metastatic colorectal adenocarcinoma in phase I/II setting. Patients and methods  We recruited 37 patients with histologically proven metastatic colorectal adenocarcinoma. UFT (300 mg/m² per day) and LV (75 mg/day) were administered orally on days 1–21. CPT-11 was administered intravenously on day 1 and 15, at an initial dose of 60 mg/m², stepping up to 150 mg/m² in a traditional phase I fashion. The treatment was repeated every 4 weeks. After patients enrolled into a phase II portion, the efficacy and toxicity of this regimen were also assessed. Results  The recommended dose of CPT-11 was determined to be 150 mg/m². Although one patient had a pulmonary embolism after 60 mg/m² of CPT-11, the treatment was well tolerated in general. The overall objective response rate was 37.8% (14/37; 95% CI, 22.5–55.2) in all patients. Median progression-free survival was 226 days (95% CI, 133–276). Conclusions  Biweekly CPT-11 plus UFT and LV had a reasonable safety profile with manageable toxicity, and had a promising activity in patients with metastatic colorectal cancer. Further trials are indicated based on the promising results observed in this study.     

Capecitabine plus oxaliplatin (xelox) in the treatment of chemotherapy-naive patients with metastatic colorectal cancer

Background Capecitabine and oxaliplatin are both synergistically active against metastatic colorectal cancer (MCRC). We evaluated our experience at two centers with capecitabine and oxaliplatin combination (XELOX) in previously untreated patients with MCRC. Patients and methods We reviewed medical records of 85 previously untreated patients with MCRC who received first-line XELOX regimen. Oxaliplatin was given at a dose of 130 mg/m² on day 1 in combination with capecitabine 1500 mg/m²/day on days 1–14 every 3 weeks. Results Seventy six of 85 patients were evaluated for response and toxicity. Patients with a follow up of less than 6 months were excluded from the study. Objective response rate was 46% including 8 complete responses (10.5%) and 27 partial responses (35.5%). Additionally, 20 patients (26.3%) had disease stabilization at least 3 months after the treatment. The patients were followed for a median 12.5 months (range 2–32). Median time to disease progression (TTP) was 11 months (range 2–27 months). Median overall survival (OS) time has not yet been reached. One-year survival rate was 66%. Toxicity was modest with infrequent grade 3–4 adverse effects. Conclusion XELOX is an active regimen against MCRC in the first-line setting with favorable toxicity profile. Our results appear to be comparable, if not superior, to the results of other reports of first-line XELOX therapy in respect to objective response rates, survival data, and safety profile. Convenience with oral administration of every 3-week schedule makes XELOX regimen a compelling therapeutic option in the treatment of first-line MCRC.     

Biologic therapies in the metastatic colorectal cancer treatment continuum--applying current evidence to clinical practice

More therapeutic options are now available than ever before for patients with metastatic colorectal cancer (mCRC) and, as such, treatment decisions have become more complex. A multidisciplinary approach is, therefore, required to effectively manage these patients. In the past few years, many trials have reported on the value of combining biological agents, such as those targeting vascular endothelial growth factor A and epidermal growth factor receptors, with chemotherapy. However, despite the plethora of information now available, the optimal treatment strategy for patients with mCRC remains unclear. Indeed, the propensity of investigators to conduct clinical trials utilising a variety of chemotherapy backbones combined with the increased complexity of retrospectively incorporating analyses of genetic mutation status (e.g. KRAS and BRAF) have led to conflicting results for seemingly similar endpoints, particularly overall survival. As a result, guidelines that have been developed, whilst having some similarities, have distinct differences in terms of suggested therapeutic combinations. Therefore, here, we review and distil the currently available data reported from phase III trials of biologic agents in the first-, second- and third-line mCRC settings.     

西妥昔单抗联合FOLFOX 4方案一线治疗转移性结直肠癌的临床观察

目的 观察西妥昔单抗联合FOLFOX 4方案一线治疗转移性结直肠癌的临床疗效和毒副反应。方法 回顾性分析2008年4月至2011年10月经组织病理学证实的转移性结直肠癌患者36例,其中治疗组（n=18）采用西妥昔单抗（500mg／m2 静滴120min,每周1次,使用6～12次）联合FOLFOX 4方案（奥沙利铂85mg／m2静滴2h,d1;左亚叶酸钙200mg／m2静滴2h,d1、d2;氟尿嘧啶400mg／m2静滴,d1、d2;氟尿嘧啶600mg／m2持续静脉泵入22h,d1、d2。14天为1周期,化疗不超过12个周期。）治疗。对照组（n=18）仅用FOLFOX 4方案化疗,同治疗组。结果 治疗组与对照组的客观缓解率分别为66.7％和22.2％（P＜0.05）,疾病控制率分别为94.4％和67.7％（P＞0.05）。治疗组和对照组痤疮样皮疹发生率分别为389％和0,其他不良反应包括骨髓抑制、恶心呕吐、神经毒性、肝脏损害及脱发等,差异均无统计学意义（P＞0.05）。结论 西妥昔单抗联合FOLFOX 4方案治疗转移性结直肠癌的近期疗效显著,毒副反应可耐受。     

多西紫杉醇为主的联合方案治疗转移性乳腺癌

目的:探讨多西紫杉醇为主的联合化疗方案治疗转移性乳腺癌的疗效及毒副反应。方法:49例转移性乳腺癌患者中,22例既往使用蒽环类治疗失败,予多西紫杉醇联合顺铂或希罗达治疗;27例既往未曾采用蒽环类治疗,予多西紫杉醇联合阿霉素治疗。21天为1周期,2周期后评价疗效,有效者化疗4周期以上。结果:49例患者中,治疗后完全缓解(CR)11例,部分缓解(PR)23例,稳定(SD)8例,进展(PD)7例,有效率为69·3%(34/49)。中位疾病进展时间为8·5个月,中位生存时间为18·3个月。主要毒副反应为白细胞减少,其中Ⅲ~Ⅳ度占51·0%。结论:多西紫杉醇为主的联合化疗方案治疗转移性乳腺癌疗效确切,毒性反应可耐受。     

转移性结直肠癌维持治疗的研究现状与治疗策略

结直肠癌是常见的恶性肿瘤之一,其发病率和死亡率分别位于第三位和第四位。大约60%的患者确诊时已处于晚期,其5年生存率在13%左右。近20年来,由于转移性结直肠癌(mCRC)晚期一线化疗方案及靶向药物的规范化应用,mCRC的治疗获得了重大突破。奥沙利铂、卡培他滨、贝伐珠单抗、西妥昔单抗等药物的应用使患者的中位生存期提高了一倍,5年生存率提高了20%。mCRC晚期一线治疗的常规模式是持续用药,直至病情进展或出现不可耐受的毒性。但是由于化疗药物的毒性累积,只有三分之一的患者能够坚持接受治疗直至病情进展。而患者在完成既定的初始化疗周期数,达到CR/PR/SD后,继续采用低剂量、低毒性的药物进行维持治疗,既可以延缓肿瘤的进展和转移,又可以减轻药物的毒副作用。目前,维持治疗已经成为mCRC晚期一线化疗后的主要治疗模式。但是,mCRC的最佳维持治疗方案仍无定论,现有的维持治疗方案仍不能找到最佳疗效与最大生活质量之间的平衡点。本文将回顾mCRC现有的维持治疗方案的临床研究,总结mCRC维持治疗现状,并对个体化的治疗策略进行讨论。     

Capecitabine maintenance therapy after first-line chemotherapy in patients with metastatic colorectal cancer

Objective  

To evaluate the efficacy and toxicity of capecitabine maintenance therapy in metastatic colorectal cancer (mCRC) patients.     

Efficacy and safety of chemotherapy combined with bevacizumab in Chinese patients with metastatic colorectal cancer: A prospective,multicenter, observational,non-interventional phase IV trial

ObjectiveBevacizumab has an important and evolving role in improving outcomes in patients with metastatic colorectal cancer (mCRC) worldwide and was approved in China in 2010. However, there are limited real-world data on the efficacy and safety of chemotherapy regimens combined with bevacizumab in Chinese patients with mCRC. This observational, phase IV trial study aimed to obtain more experience on the efficacy and safety of bevacizumab combined with chemotherapy in Chinese mCRC patients.MethodsBetween September 2013 and November 2016, patients with histologically confirmed mCRC were enrolled in a prospective, multicenter, observational, non-interventional phase IV trial at 26 centers across China. Eligible patients received different chemotherapeutic regimens combined with bevacizumab. The efficacy and safety data in the intention-to-treat study population were analyzed.ResultsA total of 611 patients were included in the efficacy analysis. The median overall survival and median progression-free survival was 18.00 and 10.05 months, respectively. The objective response rate was 21.00% and disease control rate was 89.40%. In subgroup analyses, the survival differences were observed according to metastatic status, duration of treatment and elevation in blood pressure. A total of 613 patients were evaluable for safety assessments. And 569 (92.82%) patients reported at least one adverse event (AE), and 151 (24.63%) experienced grade 3 or higher AEs. The incidence of bevacizumab-associated AEs of special interest was reported in 31 (5.06%) patients with hypertension (n=12), abscesses and fistulae (n=7), bleeding (n=6), proteinuria (n=3), gastrointestinal perforation (n=2) and venous thrombotic events (n=1).ConclusionsThis observational phase IV trial broadens our experience and knowledge of bevacizumab in the Chinese population and provides a good indication of its overall efficacy and safety. Bevacizumab in combination with chemotherapy offers clinical benefits to Chinese patients with mCRC and has an acceptable and manageable safety profile.     

A phase II study of oxaliplatin, dose-intense capecitabine, and high-dose bevacizumab in the treatment of metastatic colorectal cancer

Background

This study was designed to determine the efficacy and tolerability of a novel 2-week regimen of capecitabine, oxaliplatin (OHP), and bevacizumab in patients with chemo-naive advanced colorectal cancer.

Patients and Methods

Nineteen patients with previously untreated advanced colorectal cancer received capecitabine at 1000 mg/m² twice a day on days 1-5 and days 8-12 of a 14-day cycle, and OHP at 85 mg/m² and bevacizumab at 10 mg/kg every 2 weeks. Because of unacceptable toxicities, the capecitabine dose was reduced to 850 mg/m². Thirty-one additional patients were treated at the lower capecitabine dose. Treatment continued until disease progression, persistent intolerable toxicity, or physician and/or patient discretion.

Results

Overall, toxicities were better managed and tolerated at the 850 mg/-m² capecitabine dose. The most common treatment-related grade ≥ 3 toxicities were diarrhea and sensory neuropathy. In the first 19 subjects, the response rate was 63% (95% confidence interval [CI], 38%-84%) and 5 patients had stable disease; median progression-free survival (PFS) was 10.1 months (95% CI, 5.7-19.5 months). In the subsequent 31 patients, the response was 42% (95% CI, 25%-61%); 11 patients had stable disease and median PFS was 10.4 months (95% CI, 6.9-15.4); median overall survival was 24.8 months (95% CI, 12.9-39.7).

Conclusions

This novel regimen of capecitabine at 850 mg/m² twice a day on days 1-5 and days 8-12 and OHP at 85 mg/m²and bevacizumab at 10 mg/kg every 14 days is clinically active in advanced colorectal cancer. The toxicity profile of this regimen is consistent with the standard every-3-week dosing schedule.     

贝伐珠单抗联合FOLFOX或FOLFIRI方案治疗转移性结直肠癌的临床研究

目的 观察贝伐珠单抗联合FOLFOX或FOLFIRI方案用于转移性结直肠癌一线及二线治疗的临床疗效和毒副反应。方法 回顾性分析2005年11月至2012年8月接受贝伐珠单抗联合FOLFOX或FOLFIRI方案作为一线及二线治疗的57例转移性结直肠癌患者的临床资料。采用RECIST 1.1版评价疗效,用NCI-CTC 3.0版评价不良反应,用Kaplan-Meier法进行生存分析。结果 57例结直肠癌患者中,19例（33.3％）获PR,28例（49.2％）获SD,有效率（RR）为33.3％,疾病控制率（DCR）为82.5％。贝伐珠单抗联合化疗用于一线与二线治疗患者的RR或DCR差异均无统计学意义（P＞0.05）;贝伐珠单抗联合FOLFOX方案与FOLFIRI方案的RR或DCR差异均无统计学意义（P＞0.05）。57例患者的无进展生存期（PFS）及总生存期（OS）分别为8.83个月及14.80个月。一线与二线治疗及贝伐珠单抗联合FOLFOX方案与FOLFIRI方案的中位PFS或OS差异均无统计学意义（P＞0.05）。主要不良反应包括白细胞减少、血小板减少及恶心呕吐。贝伐珠单抗相关的不良反应主要包括高血压3例,蛋白尿1例,鼻衄2例,均为1～2级,药物可以控制。结论 贝伐珠单抗联合化疗治疗转移性结直肠癌能够提高治疗疗效,不良反应可以耐受。     

Early tumour shrinkage (ETS) and depth of response (DpR) in the treatment of patients with metastatic colorectal cancer (mCRC)

BackgroundResponse evaluation criteria in solid tumours (RECIST) are used to define degrees of response to anti-tumour agents. In retrospective analyses, early tumour shrinkage (ETS) has been investigated as an alternative early-on-treatment predictor of treatment efficacy with regard to progression-free and overall survival. While cut-off based analysis of ETS facilitates the categorisation of patients into responders and non-responders after a defined period of treatment, depth of response (DpR) serves as a continuous measure, which defines the nadir of tumour response.MethodsA systematic literature search for ‘early tumour shrinkage’ or ‘tumour size decrease’ in ‘metastatic colorectal cancer’ reported from January 2000 to July 2014 was performed. The present review summarises available data concerning ETS and DpR and evaluates their potential as predictive markers for the clinical management of patients with metastatic colorectal cancer (mCRC).ResultsA total of 10 clinical trials investigated the role of ETS as a marker of clinical outcome in patients with mCRC. In addition, DpR was investigated using the efficacy data from three of these trials. Available data show that ETS differentiates patients with high sensitivity to treatment and more favourable prognosis from a heterogeneous group of patients classified as non-ETS patients. ETS is an early indicator of the potentially achievable response. In contrast, DpR estimates the nadir of tumour response as a continuous measure, which may affect the subsequent disease history, thus translating into superior survival.ConclusionsThe concepts of ETS and DpR offer potential as clinical end-points to aid the clinical decision making process and thus further optimise mCRC patient management in the era of tailored therapy approaches.     

RAC1b overexpression correlates with poor prognosis in KRAS/BRAF WT metastatic colorectal cancer patients treated with first-line FOLFOX/XELOX chemotherapy

IntroductionChemotherapy is the principal treatment in metastatic colorectal cancer (mCRC) patients. RAC1b, a RAC1 spliced variant, is over-expressed in colorectal cancer (CRC), and impairs apoptosis by activation of nuclear-factor-KB. Since RAC1b has been associated with the BRAF^V600E mutation, associated with poor prognosis in CRC, we evaluated the role of RAC1b expression as a predictor of chemotherapy efficacy in mCRC.MethodsWe analysed KRAS and BRAF mutation, microsatellite instability and RAC1b expression in 157 mCRC patients treated with FOLFOX/XELOX in first-line therapy.ResultsKRAS mutations were detected in 46 patients (34%), 10 patients were BRAF mutant (7%) and 79 were WT for both, KRAS and BRAF (59%). RAC1b overexpression was found in 30 patients (19%). In the multivariate analysis, BRAF mutational status was a poor prognostic factor for overall survival (OS); hazard ratio (HR), 2.78 (95% confidence interval (CI), 1.35–5.72; p = 0.0057). RAC1b overexpression was a poor survival factor for OS (HR, 2.35; 95% CI, 1.2–4.59; p = 0.01) and progression-free survival (PFS) (HR, 2.4; 95% CI, 1.2–4.78; p = 0.01) in KRAS/BRAF WT mCRC patients.ConclusionsRAC1b overexpression constitutes a marker of poor prognosis in KRAS/BRAF WT mCRC patients treated with first-line FOLFOX/XELOX therapy.     

Bevacizumab in combination with FOLFIRI chemotherapy in patients with metastatic colorectal cancer: an assessment of safety and efficacy in the province of Newfoundland and Labrador

Background

In 2005, bevacizumab was approved by Health Canada for patients with metastatic colorectal cancer (mcrc). Newfoundland and Labrador was one of the first Canadian provinces to fund this agent in combination with folfiri (irinotecan, 5-fluorouracil, leucovorin) chemotherapy. In this analysis, the entire provincial bevacizumab sample for the first 2 years was assessed for overall safety and efficacy.

Methods

The medical records of 43 patients with mcrc who had received folfiri with bevacizumab were identified and reviewed. The longitudinal data collection format that was adopted assessed occurrences of adverse events after each cycle of treatment. Toxicity outcomes such as gastrointestinal (gi) perforations, bleeding, diarrhea, myelosuppression, proteinuria, and venous thromboembolic events (vtes) were collected and graded using the U.S. National Cancer Institute’s Common Terminology Criteria for Adverse Events, version 3.0. Time to treatment failure (ttf) and overall survival (os) were determined using the Kaplan–Meier method.

Results

Overall, the 43 study patients received 398 cycles of anticancer therapy (median: 6 cycles; range: 1–24 cycles). No gi perforations were identified. However, 4 bleeding events occurred (9.3%), 3 requiring permanent discontinuation of bevacizumab. Also, 6 grade 3 or 4 vtes occurred (14.0%), 3 of which required a hospital admission. In addition, grades 3 and 4 diarrhea, febrile neutropenia, and proteinuria showed cumulative incidences of 11.6%, 2.3%, and 2.3% respectively. Median ttf was 6.3 months; median os was 24.4 months.

Conclusions

Bevacizumab in combination with folfiri appears to be well tolerated, and efficacy is consistent with trial reports. However, patients should be closely monitored to avoid potentially serious events such as bleeding and vtes.     

Meta-regression of treatments for metastatic colorectal cancer: Quantifying incremental benefit from 2000 to 2012

To evaluate the overall effectiveness of treatments for metastatic colorectal cancer, a meta-regression was undertaken in which randomized studies from 2000 to 2012 were evaluated and the temporal trend for both overall survival (OS) and progression-free survival (PFS) was determined. Our literature search was essentially based on PubMed but information sources were scanned. Trials were included if a fluoropyrimidine regimen was given to at least one arm and information on PFS and OS was available. Medians for OS and PFS were our end-points. Covariates included temporal trend, arm allocation and Kirsten rat sarcoma status. In analyzing 130 treatment arms identified through our literature search, meta-regression showed an improvement with time for both OS (P < 0.001) and PFS (P < 0.001). The increase in median OS was from 14.9 mo in 2000 to 18.8 mo in 2012. Likewise, the improvement in PFS was from 5.7 to 8.1 mo. Multivariate analysis confirmed these findings. A post-hoc multivariate analysis was focused on patient arms treated with bevacizumab (n = 17) or without bevacizumab (n = 113); the multivariate-adjusted improvement attributable to bevacizumab was 1.66 mo for OS (P = 0.071) and 1.59 mo for PFS (P = 0.002). Overall, our results indicate that OS and PFS have improved from 2000 to 2012 but the extent of this improvement is small and seems to have quite a questionable clinical relevance.     

Prognostic role of sarcopenia in metastatic colorectal cancer patients during first-line chemotherapy: A retrospective study

BACKGROUNDSarcopenia is a condition characterized by decreased skeletal muscle mass due to physiological ageing or to a concomitant disease such as neoplasia. In cancer patients, a low lean body mass is suggested to be a negative prognostic factor for survival and for the development of dose-limiting chemotherapy toxicities irrespective of disease stage. AIMTo evaluate the prognostic role of sarcopenia in patients with metastatic colorectal cancer (mCRC) undergoing first-line chemotherapy.METHODSOur retrospective analysis included 56 mCRC patients who received first-line chemotherapy from 2014 to 2017 at the Medical Oncology Unit of our hospital. Computerized scans were performed before starting chemotherapy and at the first disease reassessment. Sarcopenia was assessed using the skeletal mass index = muscle area in cm²/(height in m²) calculated at the L3 vertebra. Overall survival and objective response rate were evaluated. Toxicities were analyzed during the first four cycles of therapy and graded according to Common Terminology Criteria for Adverse Events version 4.0. A loss of skeletal muscle mass ≥ 5% was considered indicative of deterioration in muscle condition.RESULTSMedian age was 67 years and 35.7% of patients were ≥ 70 years old. Fourteen patients (25%) were sarcopenic at baseline computed tomography (CT) scan (7/33 men; 7/23 women); 5/14 sarcopenic patients were ≥ 70 years old. Median follow-up was 26.8 mo (3.8-66.8 mo) and median overall survival was 27.2 mo (95%CI: 23.3-37.3). Sarcopenia was not correlated to overall survival (P = 0.362), to higher toxicities reported during the first 4 cycles of chemotherapy (P = 1.0) or to response to treatment (P = 0.221). At the first disease reassessment, a skeletal muscle loss (SML) ≥ 5% was found in 17 patients (30.3%) 3 of whom were already sarcopenic at baseline CT scan, while 7 patients became sarcopenic. SML was not correlated to overall survival (P = 0.961). No statistically significant correlation was found between baseline sarcopenia and age (P = 1.0), body mass index (P = 0.728), stage at diagnosis (P = 0.355) or neutrophil/lymphocyte ratio (P = 0.751).CONCLUSIONNeither baseline sarcopenia nor SML affected survival. In addition, baseline sarcopenia was not related to worse treatment toxicity. However, these results must be interpreted with caution due to the limited sample size.     

TOPO-1在转移性结直肠癌组织中的表达及与伊立替康化疗的相关性研究

目的　探讨拓扑异构酶1（topoisomerase1,TOPO-1）在转移性结直肠癌组织中的表达,并分析其与伊立替康（CPT-11）化疗疗效的相关性。方法 经病理活检证实为转移性结直肠癌初诊者98例,均接受FOLFIRI方案一线化疗,化疗前检测肿瘤组织TOPO-1的表达水平,分析TOPO-1表达水平与近期疗效的关系,并观察远期疗效。结果 TOPO-1 表达水平与转移性结直肠癌的临床特征无明显相关性（P＞0.05）。高表达组患者RR为52.2%（24/46）,低表达组RR为28.8%（15/52）,差异有统计学意义（P<0.05）。TOPO-1高表达组中位PFS为9.5个月（8~12个月）,低表达组为8.0个月（7~9个月）,差异有统计学意义（P=0.002）。结论 TOPO-1高表达转移性结直肠癌患者可从伊立替康化疗中获得更高的近期疗效和更长的无疾病进展生存时间,可能对伊立替康化疗更敏感。