Mismatch repair system (MMR) status correlates with response and survival in non-small cell lung cancer (NSCLC) patients

Pre-clinical data suggested a relationship between inactivation of hMLH1 and hMSH2 and resistance to drugs like cisplatin and carboplatin, but not oxaliplatin. We then hypothesised that NSCLC showing loss of expression of the mismatch repair system (MMR), could be refractory to cisplatin-based, but not to oxaliplatin-based chemotherapy. Immunohistochemical expression of hMLH1 and hMSH2 was analysed on tumour samples from 93 advanced NSCLC, receiving chemotherapy with either cisplatin or oxaliplatin in combination with gemcitabine. Patients showing loss of hMLH1 or hMSH2 expression in > or = 50% of tumour cells were deemed MMR-negative (Group A), whereas cases with a normal hMLH1 or hMSH2 expression in > 50% of the tumour cells were defined MMR-positive (Group B). No differences in the response and progression rate were found in the whole patients population and in the gemcitabine/cisplatin group for both hMLH1 and hMSH2. In the gemcitabine/oxaliplatin group response rate was 38% and 0% (p=0.04) for patients with or without loss of hMSH2 expression. Median survival according to MMR status in Groups A and B, respectively was: 17 months versus 9 months for hMLH1 (p=0.031) and 10 months versus 9 months for hMSH2 (p=0.8330). Both the difference in response rate and in median survival observed according to MMR status seem to confirm what has been suggested by preclinical studies.     

两种铂类与吉西他滨联合用于初治老年晚期非小细胞肺癌患者临床对比观察

目的:探讨顺铂或奥沙利铂与吉西他滨联用于初治老年晚期非小细胞肺癌的临床疗效及安全性差异。方法:选取初治老年晚期非小细胞肺癌患者140例,采用随机数字表法分为A组（70例）和B组（70例）。在吉西他滨基础上分别加用顺铂和奥沙利铂静脉滴注,比较两组患者临床疗效,中位无进展生存时间,治疗前后体质量、KPS评分及III-IV级不良反应发生情况等。结果:两组患者临床疗效和中位无进展时间比较差异无统计学意义（P>0.05）。两组患者治疗后体质量和KPS评分均较治疗前显著提高,且B组患者治疗后两项指标优于A组,差异有统计学意义（P<0.05）。B组患者III-IV级不良反应发生率显著低于A组,差异有统计学意义（P<0.05）。结论:相较于顺铂与吉西他滨联合,奥沙利铂与吉西他滨联合用于初治老年晚期非小细胞肺癌患者可有效提高其生活质量,降低严重不良反应发生风险,但两种化疗方案临床疗效相当。     

中晚期食管鳞癌紫杉醇联合不同铂类药加IMRT的预后分析

目的 分析食管癌铂类药联合紫杉醇+IMRT的预后,探讨较佳的化疗方案。方法 选取2008-2014年间收治的242例紫杉醇联合顺铂(68例)、奈达铂(85例)、洛铂(58例)和奥沙利铂(31例)化疗+IMRT的中晚期食管癌患者,分析4个组以及化疗周期数2、3、≥4个的预后。用Kaplan-Meier方法计算生存率并Logrank检验,用Cox模型进行多因素预后分析。结果 3年样本数168例。全组患者中位生存时间为31.1个月,3年生存率为47.4%。紫杉醇联合顺铂、奈达铂、洛铂和奥沙利铂+IMRT的3年生存率分别为46.2%、56.4%、45.7%和29.0%(P=0.090)。分层分析发现紫杉醇联合顺铂+奈达铂+洛铂+IMRT的生存率高于联合奥沙利铂+IMRT (50.1%∶29.0%,P=0.021);化疗周期数2、3、≥4个的3年生存率分别为40.1%、49.5%和50.8%(P=0.264)。多因素分析显示食管肿瘤体积和淋巴结转移最大径是影响预后的因素。结论 紫杉醇联合顺铂或奈达铂或洛铂化疗方案+IMRT的生存率高于联合奥沙利铂+IMRT,食管肿瘤体积和淋巴结转移最大径是预后影响因素。     

Predictive Role of Neutrophil Gelatinase-Associated Lipocalin in Early Diagnosis of Platin-Induced Renal Injury

Background: Acute kidney injury is an important issue in chemotherapy receiving patients an neutrophilgelatinase-associated lipocalin has been proposed as a novel marker. We here aimed to assess the role of urinarylevels for assessment after platin exposure. Materials and Methods: Patients who had treated with cisplatin orcarboplatin or oxaliplatin containg regimens were included in this study. Baseline and postchemotherapy serumurea, creatinine, urine neutrophil gelatinase-associated lipocalin and urine creatinine levels were determined.To avoid the effects of hydration during chemotherapy infusion the urinary neutrophil gelatinase-associatedlipocalin/urine creatinine ratio was used to determine acute kidney injury. Results: Of a total of 42 patientsreceiving platin compounds,14 (33.3%) received cisplatin containing regimens, 14 (33.3%) received carboplatinand 14 (33.3%) oxaliplatin. The median age was 60 (37-76) years. Nineteen of the patients (45.2%) had lungcancer, 12 (28.6%) colorectal cancer and 11 (26.2%) others. The median pre and post chemotherapy urineneutrophil gelatinase-associated lipocalin/urine creatinin ratio was 15.6 ng/mg and 35.8 ng/mg (p=0.041) in thecisplatin group, 32.5 ng/mg and 86.3 ng/mg (p=0.004) in the carboplatin group and 40.9 ng/mg and 62.3 ng/mg (p=0.243) in the oxaliplatin group. Conclusions: Nephrotoxicity is a serious side effect of chemotherapeuticagentslike cisplatin and carbopaltin, but only to a lower extent oxaliplatin. All platin compounds must be usedcarefully and urine neutrophil gelatinase-associated lipocalin measurement seems to be promising in detectingacute kidney injury earlier than with creatinine.     

138例晚期食管癌的化疗疗效和预后因素分析

背景与目的:晚期食管癌患者预后差,目前仍无标准的治疗方案,影响其预后的独立因素也不明确。本研究旨在分析晚期食管癌的化疗疗效,并探讨影响其预后的因素。方法:回顾性分析中国医学科学院中国协和医科大学肿瘤医院1984年12月至2006年4月收治的、经病理和/或细胞学确诊的138例初治晚期食管鳞癌患者的临床资料。全组患者分为新药组(含紫杉醇、健择或草酸铂)和非新药组(不含紫杉醇、健择或草酸铂)。新药组有68例,其中化疗方案中含顺铂64例(94.1%);非新药组有70例,其中化疗方案中含顺铂48例(68.6%)。对可能影响生存因素的比较采用log-rank检验,死亡相对风险的比较采用Cox比例风险模型进行计算。结果:全组138例患者的化疗有效率47.8%,中位疾病进展时间4个月,中位生存时间10个月。采用含紫杉醇或健择化疗新药组患者有效率(58.8%)明显高于非新药组(37.1%)(P=0.011)。单因素分析表明,年龄、治疗前血红蛋白水平、化疗周期数、化疗近期疗效、疾病进展时间以及治疗手段与预后相关。多因素分析表明,疾病进展时间、治疗手段、疗前血红蛋白水平是影响生存的独立预后因素。结论:紫杉醇或健择联合顺铂方案用于晚期食管癌化疗有较高的有效性。疾病进展时间、治疗手段、疗前血红蛋白水平是影响生存的独立预后因素。     

Phase II study of gemcitabine and cisplatin as first-line chemotherapy in inoperable biliary tract carcinoma.

OBJECTIVES: The prognosis for patients with unresectable biliary tract cancer is poor and existing chemotherapy is relatively ineffective. Therefore, a need exists for new, effective chemotherapeutic regimens. The aim of this study was to determine the efficacy and safety profile of gemcitabine plus cisplatin in patients with unresectable biliary tract cancer (cholangiocarcinoma) and gall bladder cancer. METHODS: From December 2000 to July 2002, 43 patients received gemcitabine 1250 mg/m(2) in a 30-min i.v. infusion on d1, 8 and cisplatin 75 mg/m(2) in a 2-h i.v. infusion on d1 (with appropriate hydration), every 3 weeks. ELIGIBILITY: Normal hematologic parameters and creatinine levels; serum bilirubin < 5 mg/dl. RESULTS: Forty-three patients enrolled; 40 were assessable (three patients were not assessable due to incomplete treatment; they chose to discontinue chemotherapy after the first cycle). There were 23 males and 17 females, median age 50 years (range 31-69), median Karnofsky PS 80%. Tumor types: cholangiocarcinoma (39), gall bladder cancer (1). Median number of chemotherapy courses was four (range 1-8). Overall response rate was 27.5% (PR in 11 pts), with 32.5% SD and/or minor response. Median survival time was 36 weeks. Grade 3 hematologic toxicity: anemia (4.33%), leukopenia (1.73%). Non-hematologic toxicity (i.e. rash, nausea, vomiting, neuropathy and myalgia) ranged from mild to moderate. CONCLUSIONS: Gemcitabine plus cisplatin is active in biliary tract carcinoma. These data warrant further investigation of single-agent gemcitabine versus gemcitabine plus cisplatin or its derivative, i.e. oxaliplatin.     

Increased survival using platinum analog combined with gemcitabine as compared to single-agent gemcitabine in advanced pancreatic cancer: pooled analysis of two randomized trials, the GERCOR/GISCAD intergroup study and a German multicenter study.

BACKGROUND: The aim was to evaluate the efficacy of gemcitabine combined with a platinum agent compared to single-agent gemcitabine in a pooled analysis of two randomized trials. METHODS: The French Multidisciplinary Clinical Research Group (GERCOR)/Italian Group for the Study of Gastrointestinal Tract Cancer (GISCAD) intergroup study comparing gemcitabine plus oxaliplatin to gemcitabine and a German multicenter trial comparing gemcitabine plus cisplatin versus gemcitabine were included in a pooled analysis based on individual patient data. RESULTS: Among 503 evaluable patients, 252 received gemcitabine plus a platinum analog (GP), while 251 patients were treated with gemcitabine alone. For progression-free survival (PFS), the pooled univariate analysis indicated a hazard ratio (HR) of 0.75 (P = 0.0030) in favour of the GP combination. The benefit from the GP combination was greatest in the subgroup of patients with performance status (PS) = 0 (HR = 0.64; P = 0.013). Also overall survival was significantly superior in patients receiving the GP combination (HR = 0.81; P = 0.031). Again, patients with PS = 0 appeared to have a greater benefit from treatment intensification (HR = 0.72; P = 0.063). CONCLUSION: The pooled analysis of the GERCOR/GISCAD intergroup study and the German multicenter study indicates that the combination of gemcitabine with a platinum analog such as oxaliplatin or cisplatin significantly improves progression-free survival and overall survival as compared to single-agent gemcitabine in advanced pancreatic cancer. The benefit seems to prevail in patients with a good performance status.     

Serum nucleosomes during neoadjuvant chemotherapy in patients with cervical cancer. Predictive and prognostic significance

Background  

It has been shown that free DNA circulates in serum plasma of patients with cancer and that at least part is present in the form of oligo- and monucleosomes, a marker of cell death. Preliminary data has shown a good correlation between decrease of nucleosomes with response and prognosis. Here, we performed pre- and post-chemotherapy determinations of serum nucleosomes with an enzyme-linked immunosorbent assay (ELISA) method in a group of patients with cervical cancer receiving neoadjuvant chemotherapy.     

Gemcitabine and cisplatin in a multimodality treatment for locally advanced non-small cell lung cancer

The role of new cytotoxic agents like gemcitabine has not yet been proven in the neoadjuvant settings. We designed a phase II study to test the feasibility of using gemcitabine and cisplatin before local treatment for stage III non-small cell lung cancer patients. Patients received three cycles of induction chemotherapy of gemcitabine (1000 mg m(-2), days 1, 8, 15) and cisplatin (90 mg m(-2), day 15) every 4 weeks before evaluation for operability. Operable patients underwent radical resection. Inoperable patients and patients who had incomplete resection received concurrent chemoradiotherapy with daily low dose cisplatin. All patients who did not progress after local treatment received three more cycles of adjuvant chemotherapy of gemcitabine and cisplatin. Fifty-two patients received induction treatment. Two patients had complete response and 31 patients had partial response (response rate 63.5%) after induction chemotherapy. Thirty-six patients (69%) were operable. Eighteen patients (35%) had their tumours completely resected. Two patients had pathological complete response. Median overall survival was 19.1 months, projected 1-year survival was 66% and 2-year survival was 34%. Three cycles of gemcitabine and cisplatin is effective and can be used as induction treatment before surgery for locally advanced non-small cell lung cancer patients.     

Induction chemotherapy with gemcitabine and oxaliplatin for locally advanced cervical carcinoma

Induction chemotherapy followed by surgery, particularly with newer agents or combinations, remains to be explored in locally advanced cervical cancer. Gemcitabine cisplatin is a very active combination for this tumor, therefore we explored the activity of gemcitabine in combination with oxaliplatin. Ten untreated patients with histologic diagnosis of cervical carcinoma and staged as IB2 to IIIB were treated with 3 21-day courses of oxaliplatin 130 mg/m day 1 and gemcitabine 1,250 mg/m days 1 and 8 followed by locoregional treatment with either surgery or concomitant chemoradiation. Response and toxicity were evaluated at the end of chemotherapy. All patients were evaluable. The overall clinical response rate was 80%, being complete in 3 patients (30%) and partial in 5 (50%). Seven (70%) patients underwent surgery, and three (30%) had chemoradiation as definitive treatment. Hematologic toxicity was moderate, with leukopenia grades III-IV in 17 and 0%; granulocytopenia grades III-IV in 23 and 3%, respectively. Eight patients had grade I oropharyngeal toxicity. At a median follow-up of 11 months (range: 10-12), all patients are disease free. Gemcitabine oxaliplatin is a very active and well-tolerated combination for locally advanced cervical cancer.     

Platinum agents and mitomycin C-specific complications in cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC)

Introduction: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been found to prolong survival in patients with peritoneal disease but is associated with significant morbidity. We evaluate the perioperative complications and the association with the chemotherapy agent used for HIPEC.

Methods: Retrospective analysis of a prospectively collected database of CRS–HIPEC cases between April 2001 and February 2016 was performed. Patients were stratified by the chemotherapy used, and perioperative complications were compared.

Results: Out of 214 CRS–HIPEC cases, 113 procedures used Mitomycin-C(MMC), 92 used cisplatin, 8 used oxaliplatin and the HIPEC regimen for one procedure was not recorded and excluded. 94 patients (44%) suffered low-grade complications (grade I–II), and 49 patients (23%) suffered high-grade complications (grade III–V). The frequency of low-grade complications for the cisplain, oxaliplatin and MMC groups were 49%, 50% and 40%, respectively, whereas that of high-grade complications were 24%, 50% and 20%, respectively. HIPEC with platinum agents was associated with a higher rate of acute renal impairment (ARI) compared to MMC (32% and 62% for cisplatin and oxaliplatin vs. 5.6% for MMC), whereas grade IV ARI requiring dialysis occurred only in the cisplatin group (5.6%). HIPEC with oxaliplatin was associated with higher rates of post-operative bleeding (25% vs. 1.1% and 0.88%). Rates of other complications did not differ significantly between the groups receiving different HIPEC regimens.

Conclusions: The overall complication rates do not significantly differ after HIPEC with MMC and platinum based agents. Renal impairment tends to be more common and of greater severity when a platinum agent is used, whereas oxaliplatin is associated with significant post-operative bleeding.     

Growth inhibition and apoptosis induction in ovarian cancer cells

Standard therapy for the treatment of ovarian cancer is radical surgery followed by radiation and/or chemotherapy using cisplatin and paclitaxel. Unfortunately, some patients relapse after this first line chemotherapy and some patients become platinum-refractory. Therefore, we analyzed two different ovarian carcinoma cell lines for their sensitivity for gamma-irradiation and treatment with cisplatin, irinotecan, paclitaxel and gemcitabine. We found that both cell lines were rather resistant against gamma-irradiation and treatment with cisplatin and irinotecan whereas paclitaxel and gemcitabine resulted in a considerable reduction of the viability of the cancer cells. Both paclitaxel and gemcitabine treatment resulted in the induction of apoptosis. This sensitivity profile might be due to a particular subset of p53, which reacted with monoclonal antibodies DO-1 and PAb1801 but not with PAb1620 and PAb421. Gemcitabine and paclitaxel are highly efficient in the induction of apoptosis in ovarian cancer cells, which express a particular subset of the growth suppressor protein p53. Thus, a sensitivity profile for each ovarian carcinoma seems to be highly recommended before starting treatment.     

吉西他滨联合铂类治疗64例晚期非小细胞肺癌临床疗效研究

目的:比较吉西他滨(gemcitabine)联合顺铂(cisplatin)、卡铂(carboplatin)和奥沙利铂(oxaliplatin)三种化疗方案对晚期非小细胞肺癌(NSCLC)的疗效和毒性反应。方法:经病理和细胞学证实的64例晚期NSCLC患者随机分为吉西他滨 顺铂(gemcitabine cisplatin,Gcis)、吉西他滨 卡铂(gemcitabine carbopl-atin,Gcarb)和吉西他滨 奥沙利铂(gemcitabine oxaliplatin,GLOHP)三组。三组均选用吉西他滨1000mg/m2静脉滴注第1、8天。GCis组:顺铂70mg/m2静脉滴注,第1天;GCarb组:卡铂AUC4～6(初治6,复治4～5),静脉滴注,第1天;GLOHP组:奥沙利铂LOHP130mg/m2静脉滴注,第1天。三组均21天为一周期,连续使用2～3周期评价疗效和毒副反应。结果:Gcis、Gcarb、GLOHP三种方案治疗晚期非小细胞肺癌的有效率分别为52.38%(11/21)、50.00%(10/20)和60.87%(14/23)(P>0.05)。三种方案毒副反应主要为可耐受的骨髓抑制、消化道反应、脱发和外周神经毒性等。结论:吉西他滨联合三种不同铂类的化疗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。     

Treatment of Stage IV(A-B) nasopharyngeal carcinoma by induction-concurrent chemoradiotherapy and accelerated fractionation: impact of chemotherapy schemes

PURPOSE: The aim of this study was to evaluate the impact of different chemotherapy regimens in patients with advanced nasopharyngeal carcinoma (NPC) treated by induction-concurrent chemoradiotherapy. METHODS AND MATERIALS: Between 1998 and 2003, 75 Stage IV(A-B) NPC patients were treated with 3 cycles of induction chemotherapy with cisplatin plus 5-fluorouracil (PF) (n = 41) or cisplatin plus gemcitabine (PG) (n = 34), followed by accelerated radiotherapy in concurrence with 2 cycles of cisplatin. In 18 (24%) patients, cisplatin was completely replaced by carboplatin in both concurrent cycles, mainly because of borderline renal functions. RESULTS: The median follow-up was 3.6 years. The 3-year locoregional failure-free survival, progression-free survival, and overall survival of the whole group were 80%, 68%, and 80% respectively. No significant difference was found between patients treated with either induction regimens. However, patients with only carboplatin in the 2 concurrent cycles had significantly inferior 3-year locoregional failure-free survival (56% vs. 86%, p = 0.014), progression-free survival (39% vs. 72%, p = 0.001), and overall survival (61% vs. 87%, p = 0.046) when compared with the rest of the group. In multivariate analysis, the complete replacement of cisplatin by carboplatin during concurrent chemoradiotherapy was still an independent adverse factor in locoregional failure-free survival (hazard ratio, 3.662; 95% CI, 1.145-11.765; p = 0.029) and progression-free survival (hazard ratio, 3.390; 95% CI, 1.443-7.937; p = 0.005). CONCLUSIONS: The more convenient PG regimen is as effective as the PF regimen as induction chemotherapy for patients with advanced NPC. Replacing cisplatin with carboplatin in the concurrent phase carries a poor prognosis.     

Rationale and Design of MILES-3 and MILES-4 Studies: Two Randomized Phase 3 Trials Comparing Single-Agent Chemotherapy Versus Cisplatin-Based Doublets in Elderly Patients With Advanced Non–Small-Cell Lung Cancer

BackgroundPlatinum-based chemotherapy is the cornerstone of treatment of advanced non-small-cell lung cancer (NSCLC) patients, but the efficacy of adding cisplatin to single-agent chemotherapy remains to be demonstrated in prospective phase III trials dedicated to elderly patients. Furthermore, the superiority of cisplatin/pemetrexed over cisplatin/gemcitabine in non-squamous NSCLC has not been confirmed prospectively. We present the rationale and design of two open-label, multicenter, randomized phase III trials for elderly patients with advanced NSCLC∶ Multicenter Italian Lung cancer in the Elderly Study (MILES)-3 and MILES-4. The aim is to evaluate the efficacy of adding cisplatin to single-agent chemotherapy (both trials) and the efficacy of pemetrexed versus gemcitabine in non-squamous tumors (MILES-4).Patients and MethodsBoth trials are dedicated to first-line therapy of patients older than 70 years with advanced NSCLC, ECOG performance status 0-1. In the MILES-3 trial, patients are randomized in a 1∶1 ratio to gemcitabine or cisplatin/gemcitabine. In the MILES-4 study patients with non-squamous histology are randomized, in a factorial design with 1∶1∶1∶1 ratio, to four arms: gemcitabine (A), cisplatin/gemcitabine (B), pemetrexed (C), cisplatin/pemetrexed (D). Two comparisons are planned∶ A+C vs B+D to test the role of cisplatin; A+B vs C+D to test the role of pemetrexed. Primary endpoint of both trials is overall survival. Secondary and exploratory endpoints include progression-free survival, response rate, toxicity, and quality of life.ConclusionsMILES-3 and MILES-4 results will add important evidence about the role of cisplatin-based doublets and pemetrexed in the first-line therapy of elderly patients with advanced NSCLC.     

Chemotherapy-induced neutropenia and treatment efficacy in advanced non-small-cell lung cancer: a pooled analysis of three randomised trials

BACKGROUND: Chemotherapy is the standard treatment for advanced non-small-cell lung cancer, and myelosuppression is a common side-effect. We aimed to assess whether haematological toxic effects could be a biological measure of drug activity and a marker of efficacy. METHODS: We analysed data for 1265 patients who received chemotherapy (vinorelbine, gemcitabine, gemcitabine and vinorelbine, cisplatin and vinorelbine, or cisplatin and gemcitabine) within three randomised trials. Primary landmark analyses were restricted to 436 patients who received all six planned chemotherapy cycles and who were alive 180 days after randomisation. Neutropenia was categorised on the basis of worst WHO grade during chemotherapy: absent (grade 0), mild (grade 1-2), or severe (grade 3-4). All statistical analyses were stratified by treatment allocation. Analyses were repeated in the out-of-landmark group (829 patients), stratifying by treatment allocation and number of chemotherapy cycles. The primary endpoint was overall survival. FINDINGS: In the landmark group, hazard ratios of death were 0.65 (0.46-0.93) for patients with severe neutropenia and 0.74 (0.56-0.98) for those with mild neutropenia. Median survival after the landmark time of 180 days was 31.4 weeks (95% CI 25.7-39.6) for patients without neutropenia compared with 42.0 weeks (32.7-59.7) for patients with severe neutropenia, and with 43.7 weeks (36.6-66.0) for those with mild neutropenia (severe vs mild vs no neutropenia p=0.0118). Findings were much the same for the out-of-landmark group. INTERPRETATION: Neutropenia during chemotherapy is associated with increased survival of patients with advanced non-small-cell lung cancer, and its absence might be a result of underdosing. Prospective trials are needed to assess whether drug dosing guided by the occurrence of toxic effects could improve efficacy of standard regimens.     

吉西他滨联合奥沙利铂与多西他赛联合奥沙利铂治疗晚期食管鳞癌的临床观察

目的：观察吉西他滨联合奥沙利铂及多西他赛联合奥沙利铂治疗晚期食管癌的疗效和毒副反应.方法：68例晚期食管癌患者均接受化疗,随机分为两组,每组34例患者：吉西他滨1000mg/m2,d1,8,静脉滴注30min;多西他赛75mg/m2,d1,奥沙利铂85mg/m2,d1.每3周为1个周期,2个周期后评价疗效及毒副反应.结果：两组没有观察到完全缓解病例.吉西他滨组：PR 19例,SD 9例,PD 6例,总有效率为55.9%,临床获益率 82.4%,中位疾病进展时间6.1个月;多西他赛组：PR 16例,SD 11例,PD 7例,总有效率为 47.1%,临床获益率 79.4%,中位疾病进展时间 5.1个月.两组有效率（55.9%vs 47.1%,P=0.47）、临床获益率（82.4%vs 79.4%,P=0.38）及中位无进展生存时间（6.1月 vs 5.1月,P=0.524 ）均无明显差异.主要毒副反应为血液学毒性和消化道反应,两组Ⅲ-Ⅳ度恶心呕吐发生率分别为14.7%和38.2%（P=0.028）,Ⅲ-Ⅳ度白细胞减少分别为11.8%和47.1%（P=0.001）,Ⅲ-Ⅳ度血小板减少分别为32.4%和8.8%（P=0.016）,肌肉酸痛发生率分别为8.8%和32.4%（P=0.016）,末梢神经麻木分别为11.8%和 35.3%（P=0.022）.结论：吉西他滨联合奥沙利铂及多西他赛联合奥沙利铂治疗晚期食管癌近期疗效相近,毒副反应均可耐受.     

Nucleosomes in serum of patients with benign and malignant diseases

High quantities of mono- and oligonucleosomes circulate in the blood of patients with malignant tumors. For their direct quantification in serum, we modified the Cell Death Detection(plus)-ELISA for its application in liquid materials. We examined sera samples from 590 persons, including 418 patients with malignant tumors, 109 patients with benign diseases and 63 healthy persons. We also observed the kinetics of the concentration of nucleosomes in serum samples from 20 patients undergoing chemotherapy and from 16 patients undergoing radiotherapy. Sera of patients with malignant tumors contained considerably higher concentrations of nucleosomes (mean = 350 arbitrary units [AU], median = 190 AU) compared with those of healthy persons (mean = 36 AU, median = 24 AU; p = 0.0001) and patients with benign diseases (mean = 264 AU, median = 146 AU; p = 0.072). Concerning the follow-up investigations, the concentration of nucleosomes in serum increased 24-72 hr after the first application of chemotherapy and 6-24 hr after the start of radiotherapy. A subsequent decrease was often correlated with regression of the tumor. In patients undergoing chemotherapy, an increase in the baseline values of circulating nucleosomes >50%, which were determined before each new therapeutic cycle, was correlated with progression of disease; all patients with disease regression showed a decrease >50% of the baseline values. In patients undergoing radiotherapy, an early decrease of the nucleosomal concentration (< or = 1 day after the initial peak during therapy) to low minimum levels (< or = 100 AU) correlated with good clinical outcome; a late decrease (>1 day) to higher minimum levels (>100 AU) was associated with a worse clinical outcome. Thus, the concentration of nucleosomes in serum might be a useful tool for monitoring the biochemical response during antitumor therapy, especially for the early estimation of therapeutic efficacy.