转移性结直肠癌患者化疗后血清癌胚抗原水平的变化

目的:观察转移性结直肠癌病人化疗前后血清癌胚抗原(CEA)水平的变化及临床意义。方法:对施行过化疗的转移性结直肠癌病人进行回顾性研究,采用CEA试剂盒以微粒子化学发光免疫分析法测定血清CEA水平,研究CEA的变化及其与一些临床特征之间的关系。结果:67例转移性结直肠癌患者中19例(28.4%)化疗开始后70天内血清CEA有所升高,71天～210天期间再复查时,其CEA水平又降至化疗前水平或更低。影像学检查提示这19例CEA短暂升高的病人均从化疗之中得到益处(11例PR,8例SD)。没有证据支持CEA短暂升高与肿瘤原发部位、肿瘤转移、肿瘤分化之间有明确的关联。结论:某些转移性结直肠癌病人化疗开始后的血清CEA水平可以有一短暂的升高,可能与临床受益有关,尚不能作为肿瘤进展的指征。     

Role of systemic chemotherapy in metastatic cervical cancer

Cervical cancer is a chemoresponsive tumor. Concurrent chemotherapy with cisplatin and radiotherapy has resulted in improved survival in patients with locally advanced cervical cancer and is now standard of care. There are many active drugs in metastatic cervical cancer with cisplatin being the most active single agent. Although response rates are significantly higher with cisplatin combinations, to date, there is no evidence to suggest this is associated with an improved survival. However, this is still an area that is attracting much research interest. The role of chemotherapy in metastatic cervical cancer will be reviewed together with some of the new areas of research.     

Efficiency and safety of trastuzumab plus chemotherapy in Her-2 overexpressing metastatic breast cancer patients

Objective： The aim of this study was to evaluate the safety and efficiency of combination of trastuzumab and chemotherapy as first line regimen in Her-2 overexpressing metastatic breast cancer （MBC） patients. The primary endpoint was overall response rate （ORR） and the second endpoint was clinical benefit rate （CBR） and toxcities. Methods： Estrogen recep- tor （ER） （-）, progesterone receptor （PR） （-）, Her-2 （＋＋＋） patients were included in the study. 126 eligible patients were divided into 2 groups, 51 of them were assigned to the Herceptin group （H group） and 75 of them were assigned to the Control group （C group）. They were treated by commonly used chemotherapy regimens with or without trastuzumab. Results： Response rate （RR） of the H group and the C group were 51.0% and 24.0% separately, and the difference were statistically significant （P 〈 0.05）. CBR of the two groups were 76.4% （H group） and 64.0% （C group）, had significant difference （P 〈 0.05）. Complete response rate （CRR） of the two groups were 21.5% and 6.6%, there were no significant difference between the two groups （P = 0.055）. Grade 3-4 cardiac toxicity were recorded in 9 patients with trastuzumab plus chemotherapy （17.6%） and 4 patients with chemotherapy （5.4%）, with no statistical significance （P = 0.054）. In the subgroup of antharcycline-containing regimens, Grade 1-4 cardiac toxicity occurred in 9 patients in the trasutuzumab combining with antharcycline-containing regimens arm [herceptin plus anthracyciine contained chemotherapy （H ＋ ACCT arm; 40.9%, g/22）], and 4 patients in the antharcycline- containing chemotherapy arm （ACCT arm; 12.5%, 4/32）. There was statistical significant difference between the two arms （P 〈 0.05）. Grade 3--4 cardiac toxicity, the occurance rates were 18.1% （4/22） in H ＋ ACCT arm and 6.3% （2/32） in ACCT arm, and there was no significant statistical difference （P = 0.352）. Grade 3-4 granulocytopenia     

Response to chemotherapy is a major parameter-influencing long-term survival of metastatic breast cancer patients

Background:In cancer patients, correlation between response tochemotherapy and gain in survival remains debated. We addressed this questionin a multivariate analysis evaluating response to chemotherapy as a factorinfluencing survival of patients with metastatic breast cancer.Patients and methods:From 1977 to 1992, 1430 patients includedin eight consecutive prospective trials of anthracycline-based first-linechemotherapy in metastatic breast cancer, were available for assessment.Median follow-up was 155 months.Results:Median survival from the date of randomisation was 24months. Objective response rate was 63.6%. A complete response (CR) wasachieved in 17% (249 patients). In a stepwise forward progressionanalysis objective response was the first independent prognostic factor forsurvival. Median survival time was 43 months for complete responders (CR), 29months for partial responders (PR), 18 months for stable disease (SD), 5months for progressive disease (PD). The probability of survival at 5 and 10years was 35% and 15% for CR's and decreased to 18%and 6% for PR's. The timing of best response (at 4 or 8 months)was not related to outcome.Conclusions:Response to an anthracycline-based chemotherapy isa major independent prognostic factor in metastatic breast cancer. The use ofthis factor to investigate new drugs seems to be pertinent. The good prognosisof complete responders justifies further evaluation of new treatmentstrategies for this patient population.     

32例化疗后接受手术治疗的晚期胃癌患者的临床分析

  目的  对晚期胃癌一线化疗后接受手术治疗的患者进行分析, 寻找影响该组患者生存的因素。  方法  回顾性分析2007年8月至2011年7月32例一线化疗后接受手术治疗的晚期胃癌患者的资料, 分析多种临床病理因素对生存的影响。生存分析采用Kaplan-Meier法, 并以Log-rank法比较组间差异, 应用Cox模型进行多因素分析。  结果  全组患者中位年龄46岁（22~74岁）, 中位生存期为19个月（4~59个月）。生存分析显示化疗疗效（PR, SD患者分别为23个月和14.5个月, P=0.045）和原发灶是否切除（切除, 未切除患者分别为23个月和5.5个月, P=0.017）与总生存相关。多因素分析未显示单一的因素与患者的生存相关。  结论  化疗有效、原发病灶可切除的经过选择的晚期胃癌患者, 可以尝试进行原发病灶的手术治疗。      

Cardiac toxicity of trastuzumab in metastatic breast cancer patients previously treated with high-dose chemotherapy: a retrospective study

HER-2 overexpression is associated to a poor prognosis in high-risk and metastatic breast cancer (MBC) patients treated with high-dose chemotherapy (HDC). HER-2 status is also a predictive factor and when trastuzumab is administered in combination with or sequentially to chemotherapy, a significant disease-free and/or overall survival improvement has been observed in HER-2+ early and MBC. Unfortunately, in both settings, trastuzumab is associated with an increased risk of cardiac dysfunction (CD). We have reviewed the clinical charts of HER-2-overexpressing MBC patients treated with trastuzumab after HDC. Age, baseline left ventricular ejection fraction (LVEF), radiation therapy on cardiac area, exposure to anthracycline, single or multiple transplant, high-dose agents, trastuzumab treatment duration were recorded as potential risk factors. In total, 53 patients have been included in the analysis. Median LVEF at baseline was 60.5%; at the end of trastuzumab (data available for 28 patients only), it was 55% (P = 0.01). Five out of the 28 (17.9%) patients experienced CD. Two out of 53 (3.8%) patients developed a congestive heart failure. Age > or = 50 years and multiple transplant procedure were potential risk factors for CD. The overall incidence of CD observed in this population of HER-2+ MBC patients treated with trastuzumab after HDC is not superior to that reported with concomitant trastuzumab and anthracyclines. However, patients with age > or = 50 years or receiving multiple course of HDC should be considered at risk for CD.     

以紫杉醇为主的联合化疗方案治疗转移性乳腺癌的临床研究

目的观察以紫杉醇为主的联合化疗方案治疗转移性乳腺癌的近期疗效和不良反应。方法既往未用过蒽环类化疗者选用TE方案:表阿霉素70~80mg/m2,静滴,第1天,紫杉醇135~175mg/m2,静滴,第2天。既往用过蒽环类化疗者选用TP方案:紫杉醇135~175mg/m2,静滴,第1天,DDP80mg/m2,静滴,分三天用(第2、3、4天)。21~28天为一周期,至少治疗2周期。中位化疗周期数3个(2~6周期)。结果全组70例,CR7例(10.0%),PR36例(51.4%),SD24例(34.3%),PD3例(4.3%),总有效率61.4%。TE方案有效率61.2%,TP方案有效率62.8%。中位肿瘤进展时间TTP9.8个月,中位生存期17.5个月。主要不良反应为骨髓抑制和消化道反应。结论以紫杉醇为主的联合化疗方案对转移性乳腺癌有较好的疗效,毒副反应能忍受,对蒽环类耐药及对铂类抗药的晚期乳腺癌也有很好的疗效。     

贝伐珠单抗联合一线化疗晚期转移性结直肠癌的临床观察

目的：观察贝伐珠单抗联合一线化疗对晚期结直肠癌（metastatic colorectal cancer, mCRC）的疗效和毒副作用。方法30例经组织或细胞病理学证实的 mCRC 患者接受贝伐珠单抗与一线化疗药物联合治疗。贝伐珠单抗剂量为5 mg／kg 每2周重复,或7．5 mg／kg 每3周重复。一线化疗方案：18例联合 L-OHP 为主方案（FOLFOX 方案或者 CapeOx 方案）,12例联合 CPT-11为主方案（FOLFIRI方案）。评估疗效和不良反应并随访生存信息。结果30例中无 CR 患者,PR 15例（50．0％）,SD 10例（33．3％）,PD 5例（16．7％）;客观有效率50．0％,疾病控制率83．3％;中位无进展生存时间为10．809个月（95％CI：4．079～15．921）。贝伐珠单抗相关不良反应主要为高血压3例、鼻衄1例、蛋白尿1例。另有2例出现血液性毒性,考虑和化疗相关,接受 CPT-11方案者中4例出现迟发型腹泻。但上述副反应程度较轻,经对症处理后均可缓解,未影响治疗。结论贝伐珠单抗联合一线化疗对 mCRC 的疗效确切,不良反应发生率低、程度较轻,患者耐受性可,是mCRC一线治疗的理想选择。     

Raltitrexed-eloxatin salvage chemotherapy in gemcitabine-resistant metastatic pancreatic cancer

Limited information on salvage treatment in patients affected by pancreatic cancer is available. At failure, about half of the patients present good performance status (PS) and are candidate for further treatment. Patients >18 years, PS >or=50, with metastatic pancreatic adenocarcinoma previously treated with gemcitabine-containing chemotherapy, and progression-free survival (PFS) <12 months received a combination of raltitrexed (3 mg m(-2)) and oxaliplatin (130 mg m(-2)) every 3 weeks until progression, toxicity, or a maximum of six cycles. A total of 41 patients received 137 cycles of chemotherapy. Dose intensity for both drugs was 92% of the intended dose. Main grade >2 toxicity was: neutropenia in five patients (12%), thrombocytopenia, liver and vomiting in three (7%), fatigue in two (5%). In total, 10 patients (24%) yielded a partial response, 11 a stable disease. Progression-free survival at 6 months was 14.6%. Median survival was 5.2 months. Survival was significantly longer in patients with previous PFS >6 months and in patients without pancreatic localisation. A clinically relevant improvement of quality of life was observed in numerous domains. Raltitrexed-oxaliplatin regimen may constitute a treatment opportunity in gemcitabine-resistant metastatic pancreatic cancer. Previous PFS interval may allow the identification of patients who are more likely to benefit from salvage treatment.     

Molecular markers of response and toxicity to FOLFOX chemotherapy in metastatic colorectal cancer

Background:

To investigate three genetic alterations (TP53 mutation, Kras mutation and microsatellite instability (MSI)) and three polymorphisms (methylene tetrahydrofolate reductase (MTHFR) C677T, excision repair cross complementing group 1 (ERCC1)-118 and X-ray repair cross complementing group 1 (XRCC1)-399) for their ability to predict response, survival and toxicity to FOLFOX first line chemotherapy in the treatment of metastatic colorectal cancer (mCRC).

Methods:

Tumour tissues from 118 mCRC patients who underwent FOLFOX treatment from three successive phase II trials were evaluated for mutations in TP53 (exons 5–8) and Kras (codons 12 and 13) and for MSI using PCR-based analysis. Genotyping for common single nucleotide polymorphisms in the MTHFR (codon 677), ERCC1 (codon 118) and XRCC1 (codon 399) genes was also carried out using PCR techniques. These genetic markers were correlated with clinical response, survival and toxicity to treatment.

Results:

Patients with the T allele of ERCC1-118 showed significantly worse progression-free survival in univariate analysis (HR=2.62; 95% CI=1.14–6.02; P=0.02). None of the genetic alterations or polymorphisms showed significant association with clinical response to FOLFOX. The MTHFR, ERCC1 and XRCC1 polymorphisms showed no associations with overall haematological, gastrointestinal or neurological toxicity to FOLFOX, although MTHFR 677 TT genotype patients showed a significantly higher incidence of grade 3 or 4 diarrhoea (26%) compared with CC or CT genotype patients (6%, P=0.02).

Conclusions:

The ERCC1-118 and MTHFR C677T polymorphisms were associated with progression and severe diarrhoea, respectively, after FOLFOX treatment in mCRC. Although our findings require confirmation in large prospective studies, they reinforce the concept that individual genetic variation may allow personalized selection of chemotherapy to optimize clinical outcomes.     

含卡培他滨联合方案一线化疗后卡培他滨维持治疗转移性乳腺癌临床观察

目的:探讨转移性乳腺癌含卡培他滨联合方案一线化疗后继续卡培他滨维持化疗的疗效和毒副反应。方法:入组20例转移性乳腺癌患者,一线采用多西他赛/吉西他滨/长春瑞滨联合卡培他滨化疗6个周期,疗效评价无进展的患者采用卡培他滨维持化疗持续到疾病进展或出现不能耐受毒副反应为止。结果:一线治疗CR 1例,PR 7例,SD 12例,卡培他滨平均维持化疗周期为10个周期。中位PFS为12.2个月,中位TTP为7.7个月,中位OS为20.2个月。主要毒副反应为手足综合征、骨髓抑制、腹泻等,均可控制。结论:卡培他滨可作为转移性乳腺癌的维持治疗,可改善患者生存,毒副反应轻。     

Chemotherapy of metastatic triple negative breast cancer: Experience of using platinum-based chemotherapy

The results of recent studies investigating the role of platinum-based chemotherapy (PBCT) in metastatic triple-negative breast cancer (mTNBC) were conflicting. We retrospectively investigated a large cohort (n = 379) of mTNBC to re-evaluate the role of platinums. Longer PFS was found in patients with PBCT than those with non-PBCT (7.8 vs. 4.9 months, P < 0.001) as first-line chemotherapy, but no statistical difference of OS was observed. Compared with other kinds of platinum, cisplatin-based regimens as the first-line chemotherapy showed better PFS (8.0 vs. 4.3 months, P = 0.03) and better ORR. Introduction of ≥2 lines, rather than 1 line, of PBCT can result in better OS when compared with no introduction of PBCT during the whole treatment. If considering the timing of intervention of PBCT, first-line introduction and later line introduction of PBCT did not make any difference in OS among patients with only one line PBCT during the whole treatment. We concluded that PBCT with only 1 line during the whole treatment might not be necessary for unselected mTNBC with the exception of an urgent demand to control disease or symptoms, however, ≥2 lines of PBCT did prolong OS.     

Phase II study of intensive chemotherapy with autologous bone marrow transplantation in patients in complete remission of disseminated breast cancer

SummaryBackground This trial studied the disease-free survival after high-dose chemotherapy in patients in complete remission of metastatic breast cancer.Patients and methods Thirty women, mean age 42.2 years (range 33–55) with metastatic breast cancer, received high-dose chemotherapy in a phase II study. Patients were eligible if they were 55 years of age, had achieved complete remission within 6 months of the initiation of chemotherapy, and had a WHO performance scale of 0 or 1. The high-dose regimen consisted of melphalan 180 mg/m² and mitoxantrone 60 mg/m² both divided over 3 days. On day 7 bone marrow and/or peripheral stem cells were infused. After bone marrow recovery, external beam radiation was administered to sites of previous metastatic disease in 15 patients.Results Apart from leuko- and thrombocytopenia, mucositis was the major side effect. One patient died during the bone marrow transplant period due to an aspergillus infection. The median follow-up since highdose chemotherapy is 25 months (range 13 to 56 months). The median disease-free survival since high-dose chemotherapy is 27 months and the disease free survival is still 43% with an overall survival of 53% at 3 years. In two patients tumor relapse occurred only in the brain; in one patient the only relapse sign was a meningeal carcinosis. At the moment 17 patients are disease-free (13+–56+) months after high-dose chemotherapy.Conclusion Until now this high-dose regimen in selected patients with complete remission after induction chemotherapy for metastatic breast cancer has a promising disease free survival.     

A phase II study of cisplatin and vinorelbine in patients with metastatic breast cancer.

BACKGROUND: To evaluate the efficacy and safety of the combination of cisplatin and vinorelbine in metastatic breast cancer. PATIENTS AND METHODS: Cisplatin (80 mg/m(2) day 1) and vinorelbine (25 mg/m(2) days 1 and 8) were administrated every 3 weeks to 52 patients (mean age 57 years; range 35-75 years) with metastatic breast cancer. Thirty-two patients were previously untreated for metastatic disease. Treatment was repeated for a maximum of six cycles. RESULTS: Objective responses were obtained in 27 patients (52.9%; complete response 9.8%). The response rate was similar in pretreated and untreated patients (50% and 54.7%, respectively; P = 0.7). ECOG performance status was good (grade 0 or 1) in 55.7% of patients at baseline assessment and in 90.3% at the end of treatment (P = 0.0001). Median time to progression was 8.5 months (8.5 months in first-line and 8.7 months in second-line patients). Median survival was 16.6 months (21.2 months in first-line and 16.1 months in second-line patients). Grade 3/4 toxicity included neutropenia (44% in first-line, 60% in second-line patients), nausea (17.3%), anemia (17%), asthenia (3.8%) and thrombocytopenia (1.9%). There were no cases of febrile neutropenia or treatment-related deaths. Alopecia did not develop in any of the patients. CONCLUSIONS: Cisplatin plus vinorelbine is active and tolerable in metastatic breast cancer, in untreated and pretreated patients.     

Clinical efficacy of S-1 in pretreated metastatic breast cancer patients

Background: S-1, an oral fluoropyrimidine carbamate, is an active and well-toleratedagent against solid cancer. However, the clinical efficacy ofS-1 in patients with metastatic breast cancer has not been determined. Methods: We retrospectively evaluated the efficacy of S-1 and identifiedits adverse effects in patients with metastatic breast cancerwho had failed to respond to prior chemotherapy regimens. Allthe patients were treated at the National Cancer Center Hospitaland received S-1 twice daily at a dose of 80 mg/m² for4 weeks, followed by a 2-week rest interval. Results: Between 2003 and 2007, 37 women with metastatic breast cancerreceived S-1 as a third line or greater chemotherapy regimen.All the patients had been previously treated with both anthracyclinesand taxanes prior to S-1 chemotherapy. The median order of S-1administration was as a fifth-line treatment, and 23 patients(62%) received S-1 as their final anticancer drug. One (3%)partial response and two (5%) stable diseases were observed.The median time to progression (TTP) was 84 days. Grade 2 adverseevents, such as diarrhea, stomatitis and neutropenia occurredin 5 (16%), 1 (3%) and 1 (3%) patients, respectively. Conclusions: S-1 was safety administered to heavily treated metastatic breastcancer patients with limited efficacy. Further evaluation ofS-1 is necessary to elucidate its clinical role in breast cancertreatment.     

长春瑞滨加表柔比星方案治疗转移性乳腺癌

目的 :研究长春瑞滨 (NVB)和表柔比星 (e ADM)联合化疗方案在转移性乳腺癌治疗中的疗效和毒副反应。方法 :采用NVB 2 5mg/m2 ,第 1、8天 ,e ADM 6 0mg/m2 第 1天 ,每 2 1天为一周期 ,共用 2～ 4周期 ,随访 6～37个月。结果 :2 7例患者 37处转移灶中 ,完全缓解 (CR) 37.84 % (14 /37) ,部分缓解 (PR) 16 .2 2 % (6 /37) ,疾病稳定 (SD) 37.84 % (14 /37) ,SD≥ 6个月者 2 1.6 2 % (8/37)。疾病进展 (PD) 8.11% (3/37)。客观有效率 (ORR为CR PR) 5 4 .0 5 % ,临床获益率 (CR PR SD≥ 6个月 )为 75 .6 8% ,中位疾病进展时间TTP为 6 .9个月。对锁骨上淋巴结转移的有效率最高达 90 .91%。毒性反应主要为白细胞减少、脱发和周围静脉炎。Ⅲ～Ⅳ度白细胞减少发生率为 74 .0 7% ,Ⅲ～Ⅳ度静脉炎的发生率为 11.11%。结论 :长春瑞滨加表柔比星方案在转移性乳腺癌治疗中疗效显著 ,不良反应可耐受。     

Quality of life in metastatic breast cancer patients under chemotherapy or supportive care: a single-institution comparative study

The aim of the present study was to evaluate quality of life (QoL) parameters in patients with metastatic breast cancer (MBC) and assess the potential differences between patients receiving chemotherapy and those undergoing supportive care interventions. In total, 210 women with MBC were enrolled in this prospective, randomized, single-institution study. The primary outcome of the trial was QoL assessment, using the self-administered European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30, version 3) and Quality of Life Questionnaire Breast 23 (QLQ-BR23) questionnaires. Quality of life was found to be statistically better (P = 0.008) in MBC patients receiving chemotherapy than those under only supportive care. Statistically significant differences in favour of chemotherapy were also found in functioning subscales, symptom single-item questions and sexual functioning. Our findings suggest that chemotherapy in MBC patients with good performance status is the more rational therapeutic approach in terms of QoL improvement.     

HCPT联合L-OHP方案治疗复发转移结直肠癌的近期临床疗效

背景与目的:虽然含氟尿嘧啶(5-fluarouracil,5-FU)联合方案是目前治疗结直肠癌的标准方案,但是作为二线治疗的疗效不高,探索新的替代方案显得十分必要。本研究拟应用羟基喜树碱(hydroxycampothecin,HCPT)联合草酸铂(oxaliplatin,L-OHP)方案治疗复发转移结直肠癌,并观察其近期疗效、不良反应及1年生存率。方法:47例经病理学检查证实的复发转移结直肠癌,采用HCPT L-OHP方案治疗86个周期,HCPT6mg/m2 NS500ml,静脉滴注d1～4;L-OHP130mg/m2 5%GS500ml,静脉滴注d1。每例治疗2个周期后进行近期临床疗效和不良反应评定,两次化疗间隔为3周。结果:38例可进行疗效评价,总有效率(CR PR)为36.8%(14/38)。化疗后KPS改善和显著改善者20例,占52.6%。白细胞下降59周期,占68.6%,其中Ⅲ～Ⅳ度白细胞下降18周期,占30.5%;腹泻48周期,占55.8%,其中Ⅲ～Ⅳ度腹泻18周期,占37.5%。1年生存率为40.0%,中位总生存期(medianoverallsurvival,mOS)和中位无进展生存期(medianprogressionfreesurvival,mPFS)分别为11.7和7.8个月。结论:HCPT L-OHP方案治疗一线化疗后复发的结直肠癌病例有较好的近期临床疗效,主要不良反应是白细胞下降和腹泻。