吉西他滨膀胱灌注治疗复发性浅表性膀胱肿瘤的安全性与有效性

目的 评价吉西他滨膀胱灌注化疗治疗常规膀胱灌注化疗(包括丝裂霉素、表阿霉素和羟基喜树碱)失败的非肌层浸润性膀胱癌(NMIBC)的安全性及有效性.方法 将72例在持续常规膀胱灌注化疗1年内出现肿瘤复发的NMIBC患者分为A、B、C 3组,每组24例.A组给予吉西他滨1000 mg灌洗,B组给予吉西他滨2000 mg灌洗,C组继续采用原化疗方案灌洗.观察并记录肿瘤复发时间及化疗不良反应.结果 A、B、c组患者的2年肿瘤无复发生存率分别为66.7%、75.0%和45.8%,采用吉西他滨灌洗患者的2年无瘤生存率达70.8%,显著高于传统化疗方案(45.8%,P<0.05),但A组与B组间未见明显差异.A组与B组中各有I例患者发生肾功能不全,其余不良反应主要为尿频、尿急、尿痛、血尿等,经对症治疗后缓解,各组间未见有明显差异,未发生严重的血液学不良反应.结论 对于常规膀胱灌注化疗后复发的NMIBC患者可考虑采用吉西他滨膀胱灌注化疗,但需注意观察患者的肾功能改变.     

吉西他滨膀胱灌注治疗复发性浅表性膀胱肿瘤的安全性与有效性

目的 评价吉西他滨膀胱灌注化疗治疗常规膀胱灌注化疗(包括丝裂霉素、表阿霉素和羟基喜树碱)失败的非肌层浸润性膀胱癌(NMIBC)的安全性及有效性.方法 将72例在持续常规膀胱灌注化疗1年内出现肿瘤复发的NMIBC患者分为A、B、C 3组,每组24例.A组给予吉西他滨1000 mg灌洗,B组给予吉西他滨2000 mg灌洗,C组继续采用原化疗方案灌洗.观察并记录肿瘤复发时间及化疗不良反应.结果 A、B、c组患者的2年肿瘤无复发生存率分别为66.7%、75.0%和45.8%,采用吉西他滨灌洗患者的2年无瘤生存率达70.8%,显著高于传统化疗方案(45.8%,P<0.05),但A组与B组间未见明显差异.A组与B组中各有I例患者发生肾功能不全,其余不良反应主要为尿频、尿急、尿痛、血尿等,经对症治疗后缓解,各组间未见有明显差异,未发生严重的血液学不良反应.结论 对于常规膀胱灌注化疗后复发的NMIBC患者可考虑采用吉西他滨膀胱灌注化疗,但需注意观察患者的肾功能改变.     

复发卵巢上皮性癌的治疗与预后分析

Objective To discuss the prognostic factors of recurrent ovarian epithelial carcinoma and to analyze the curative effect of post-relapse treatment.Methods The clinical records of 293 patients with ovarian epithelial carcinoma were reviewed retrospectively.There were 199 recurrent cases during the following up.Results All the 199 patients received chemotherapy.And 173 patients only received chemotherapy.16 patients received surgery and chemotherapy and the other 10 patients received radiotherapy and chemotherapy.158 patients received platinum-based chemotherapy again and 41 patients received chemotherapy without platinum.The response rate of all the patients was 43.7%(87/199),the response rate of only chemotherapy was 39.9%(69/173),the response rate of surgery and chemotherapy was 75.0%(12/16),and the response rate of radiotherapy and chemotherapy was 60.0%(6/10).The patients were divided into four groups according to the progression free interval(PFI).The response rates in groups that PFI ≤6 months,7-12 months,13-24 months and ＞24 months were 5.1%,47.2%,82.1% and 96.0%,respectively.The median survival time in the 16 patients received second cyto-reductive surgery was 41 months.Multivariate analysis revealed that PFI was significantly correlated with prognosis of recurrent ovarian epithelial carcinoma(OR =0.589,P =0.021).Conclusion PFI is an individual prognostic factor for survival of recurrent ovarian epithelial carcinoma.PFI is significantly associated with the response rate of chemotherapy.Optimal secondary cytoreductive surgery may improve the overall survival of recurrent patients.The response rate of paclitaxel plus platinum chemotherapy in platinum-sensitive patients is higher than that of other platinum-based chemotherapy.     

A multi-institutional retrospective study of hyperthermic plus intravesical chemotherapy versus intravesical chemotherapy treatment alone in intermediate and high risk nonmuscle-invasive bladder cancer

Objective:To compare the efficacy and safety of hyperthermic intravesical chemotherapy(HIVEC)and intravesical chemotherapy(IVEC)in patients with intermediate and high risk nonmuscle-invasive bladder cancer(NMIBC)after transurethral resection.Methods:We included 560 patients diagnosed with primary or recurrent NMIBC between April 2009 and December 2015 at 1 of 6 tertiary centers.We matched 364 intermediate or high risk cases and divided them into 2 groups:the HIVEC+IVEC group[chemohyperthermia(CHT)composed of 3 consecutive sessions followed by intravesical instillation without hyperthermia]and the IVEC group(intravesical instillation without hyperthermia).The data were recorded in the database.The primary endpoint was 2-year recurrence-free survival(RFS)in all NMIBC patients(n=364),whereas the secondary endpoints were the assessment of radical cystectomy(RC)and 5-year overall survival(OS).Results:There was a significant difference in the 2-year RFS between the two groups in all patients(n=364;HIVEC+IVEC:82.42%vs.IVEC:74.18%,P=0.038).Compared with the IVEC group,the HIVEC+IVEC group had a lower incidence of RC(P=0.0274).However,the 5-year OS was the same between the 2 groups(P=0.1434).Adverse events(AEs)occurred in 32.7%of all patients,but none of the events was serious(grades 3–4).No difference in the incidence or severity of AEs between each treatment modality was observed.Conclusions:This retrospective study showed that HIVEC+IVEC had a higher 2-year RFS and a lower incidence of RC than IVEC therapy in intermediate and high risk NMIBC patients.Both treatments were well-tolerated in a similar manner.     

Re-challenge chemotherapy with gemcitabine plus carboplatin in patients with non-small cell lung cancer

Despite recent improvements to current therapies and the emergence of novel agents to manage advanced non-small cell lung cancer(NSCLC),the patients′overall survival remains poor.Re-challenging with first-line chemotherapy upon relapse is common in the management of small cell lung cancer but is not well reported for advanced NSCLC.NSCLC relapse has been attributed to acquired drug resistance,but the repopulation of sensitive clones may also play a role,in which case re-challenge may be appropriate.Here,we report the results of re-challenge with gemcitabine plus carboplatin in 22 patients from a single institution who had previously received gemcitabine plus platinum in the first-line setting and had either partial response or a progression-free interval of longer than 6 months.In this retrospective study,the charts of patients who underwent second-line chemotherapy for NSCLC in our cancer center between January 2005 and April 2010 were reviewed.All the patients who received a combination of gemcitabine and carboplatin for re-challenge were included in the study.These patients were offered second-line treatment on confirmation of clear radiological disease progression.The overall response rate was 15%and disease control rate was 75%.The median survival time was 10.4 months,with 46%of patients alive at 1 year.These results suggest that re-challenge chemotherapy should be considered in selected patients with radiological partial response or a progression-free survival of longer than 6 months to the initial therapy.     

吉西他滨膀胱灌注化疗对非肌层浸润性膀胱癌患者经尿道膀胱肿瘤电切术术后复发的影响

目的 探讨吉西他滨膀胱灌注化疗对非肌层浸润性膀胱癌(NMIBC)患者经尿道膀胱肿瘤电切术(TURBT)术后复发的影响.方法 依据膀胱灌注化疗药物将76例NMIBC患者分为研究组(n=42)和对照组(n=34),两组患者均接受TURBT术,术后研究组患者接受吉西他滨灌注化疗,对照组患者接受吡柔比星灌注化疗.比较两组患者膀...     

TTC及FTC方案新辅助化疗治疗乳腺癌的疗效分析

Objective To investigate the efficacy of TTC and FTC regimens as neoadjuvant chemotherapy in breast cancer. Methods Collecting clinical data of 325 patients received neoadjuvant chemotherapy with TIC and FTC regimens from June 2004 to April 2008, among them 138 patients received neoadjuvant chemotherapy with TTC regimen in one group, and 187 patients received neoadjuvant chemotherapy with CTF regimen in the other group. The expression of Topo Ⅱ a in specimen of 325 patients before neoadjuvant chemotherapy were detected by immunohistochemical method. Results Among the 325 cases of neoadjuvant chemotherapy, the overall response rate (RR) was 87.7 % in TIC arm and 67.4 % in FTC arm (P=0.000), but in the group of Topo Ⅱ a(+) Her-2(-), the overall response rate (RR) was 87.8 % in TTC arm and 79.4 % in FTC arm (P=0.266), and in the groups of Topo Ⅱ a(-), there was statistical significance; the pathologic complete response rate (pCR) was 13.7 % in TIC ann and 11.2 % in CTF ann (P=0.491). Conclusion TIC regimen is superior to FTC regimen in the response rate of neoadjuvant chemotherapy, but patients with negative expression of Topo Ⅱ a may get more benefits from 9eoadjuvant taxane and anthracycline chemotherapy.     

TTC及FTC方案新辅助化疗治疗乳腺癌的疗效分析

Objective To investigate the efficacy of TTC and FTC regimens as neoadjuvant chemotherapy in breast cancer. Methods Collecting clinical data of 325 patients received neoadjuvant chemotherapy with TIC and FTC regimens from June 2004 to April 2008, among them 138 patients received neoadjuvant chemotherapy with TTC regimen in one group, and 187 patients received neoadjuvant chemotherapy with CTF regimen in the other group. The expression of Topo Ⅱ a in specimen of 325 patients before neoadjuvant chemotherapy were detected by immunohistochemical method. Results Among the 325 cases of neoadjuvant chemotherapy, the overall response rate (RR) was 87.7 % in TIC arm and 67.4 % in FTC arm (P=0.000), but in the group of Topo Ⅱ a(+) Her-2(-), the overall response rate (RR) was 87.8 % in TTC arm and 79.4 % in FTC arm (P=0.266), and in the groups of Topo Ⅱ a(-), there was statistical significance; the pathologic complete response rate (pCR) was 13.7 % in TIC ann and 11.2 % in CTF ann (P=0.491). Conclusion TIC regimen is superior to FTC regimen in the response rate of neoadjuvant chemotherapy, but patients with negative expression of Topo Ⅱ a may get more benefits from 9eoadjuvant taxane and anthracycline chemotherapy.     

TTC及FTC方案新辅助化疗治疗乳腺癌的疗效分析

Objective To investigate the efficacy of TTC and FTC regimens as neoadjuvant chemotherapy in breast cancer. Methods Collecting clinical data of 325 patients received neoadjuvant chemotherapy with TIC and FTC regimens from June 2004 to April 2008, among them 138 patients received neoadjuvant chemotherapy with TTC regimen in one group, and 187 patients received neoadjuvant chemotherapy with CTF regimen in the other group. The expression of Topo Ⅱ a in specimen of 325 patients before neoadjuvant chemotherapy were detected by immunohistochemical method. Results Among the 325 cases of neoadjuvant chemotherapy, the overall response rate (RR) was 87.7 % in TIC arm and 67.4 % in FTC arm (P=0.000), but in the group of Topo Ⅱ a(+) Her-2(-), the overall response rate (RR) was 87.8 % in TTC arm and 79.4 % in FTC arm (P=0.266), and in the groups of Topo Ⅱ a(-), there was statistical significance; the pathologic complete response rate (pCR) was 13.7 % in TIC ann and 11.2 % in CTF ann (P=0.491). Conclusion TIC regimen is superior to FTC regimen in the response rate of neoadjuvant chemotherapy, but patients with negative expression of Topo Ⅱ a may get more benefits from 9eoadjuvant taxane and anthracycline chemotherapy.     

TTC及FTC方案新辅助化疗治疗乳腺癌的疗效分析

Objective To investigate the efficacy of TTC and FTC regimens as neoadjuvant chemotherapy in breast cancer. Methods Collecting clinical data of 325 patients received neoadjuvant chemotherapy with TIC and FTC regimens from June 2004 to April 2008, among them 138 patients received neoadjuvant chemotherapy with TTC regimen in one group, and 187 patients received neoadjuvant chemotherapy with CTF regimen in the other group. The expression of Topo Ⅱ a in specimen of 325 patients before neoadjuvant chemotherapy were detected by immunohistochemical method. Results Among the 325 cases of neoadjuvant chemotherapy, the overall response rate (RR) was 87.7 % in TIC arm and 67.4 % in FTC arm (P=0.000), but in the group of Topo Ⅱ a(+) Her-2(-), the overall response rate (RR) was 87.8 % in TTC arm and 79.4 % in FTC arm (P=0.266), and in the groups of Topo Ⅱ a(-), there was statistical significance; the pathologic complete response rate (pCR) was 13.7 % in TIC ann and 11.2 % in CTF ann (P=0.491). Conclusion TIC regimen is superior to FTC regimen in the response rate of neoadjuvant chemotherapy, but patients with negative expression of Topo Ⅱ a may get more benefits from 9eoadjuvant taxane and anthracycline chemotherapy.     

吉西他滨膀胱灌注预防高危非肌层浸润性膀胱癌术后复发的疗效观察

目的观察吉西他滨膀胱灌注预防高危非肌层性浸润膀胱癌术后复发的疗效。方法90例高危非肌层浸润性膀胱癌经尿道膀胱肿瘤电切(TURBt)术后患者随机分为两组,每组45例,分别采用吉西他滨(治疗组)和吡柔比星(对照组)膀胱灌注。术后定期行膀胱镜检查,观察两组患者肿瘤复发情况及不良反应。结果治疗组患者随访期间有7例复发,总复发率为15.5%;对照组患者随访期间有16例复发,总复发率为35.5%,两组差异有统计学意义(P<0.05)。治疗组发生不良反应10例,对照组发生不良反应9例,主要为尿频、尿急、尿痛和血尿等,对症治疗后缓解,两组患者均未发生严重不良反应。结论 TURBt术后膀胱灌注吉西他滨预防高危非肌层浸润性膀胱癌术后复发的疗效确切,患者耐受性好,是较理想的膀胱灌注化疗药。     

吡柔比星与吉西他滨膀胱灌注化疗治疗膀胱癌的疗效比较

目的:评价吡柔比星与吉西他滨膀胱内灌注预防膀胱癌术后复发的疗效。方法:将42例保留膀胱手术治疗的膀胱癌患者分为A、B组,A组24例,B组18 例。分别使用吡柔比星与吉西他滨进行预防灌注,全部患者均术后即刻膀胱内灌注化疗,每周1次,共6次;以后每月1次直至1~2年,并做随访和疗效比较。结果:A、B两组生存率均为100%;A组复发率为25%（6/24）,B组复发率为27.8%（5/18),两组患者2年生存率、复发率比较差异无显著性意义（P>0.05）。A组和B组用药后膀胱刺激症状发生率、尿道狭窄发生率、全身不良反应发生率比较差异无显著性意义（P>0.05)。结论:吡柔比星与吉西他滨均可降低膀胱癌术后复发的机率,两者疗效无明显差异。膀胱内灌注预防浅表性膀胱癌术后复发近期疗效满意,副作用较轻,耐受性良好。     

Preclinical analyses of intravesical chemotherapy for prevention of bladder cancer progression

There is a critical need to identify treatment options for patients at high risk for developing muscle invasive bladder cancer that avoid surgical removal of the bladder (cystectomy). In the current study, we have performed preclinical studies to investigate the efficacy of intravesical delivery of chemotherapy for preventing progression of bladder cancer. We evaluated three chemotherapy agents, namely cisplatin, gemcitabine, and docetaxel, which are currently in use clinically for systemic treatment of muscle invasive bladder cancer and/or have been evaluated for intravesical therapy. These preclinical studies were done using a genetically-engineered mouse (GEM) model that progresses from carcinoma in situ (CIS) to invasive, metastatic bladder cancer. We performed intravesical treatment in this GEM model using cisplatin, gemcitabine, and/or docetaxel, alone or by combining two agents, and evaluated whether such treatments inhibited progression to invasive, metastatic bladder cancer. Of the three single agents tested, gemcitabine was most effective for preventing progression to invasive disease, as assessed by several relevant endpoints. However, the combinations of two agents, and particularly those including gemcitabine, were more effective for reducing both tumor and metastatic burden. Our findings suggest combination intravesical chemotherapy may provide a viable bladder-sparing treatment alternative for patients at high risk for developing invasive bladder cancer, which can be evaluated in appropriate clinical trials.     

卡介苗、铜绿假单胞菌交替膀胱灌注预防高危非肌层浸润性膀胱癌术后复发的疗效及安全性

目的:分析卡介苗(bacillus calmette guerin, BCG)、铜绿假单胞菌(pseudomonas aeruginosa, PA)-MSHA菌毛株交替膀胱灌注对高危非肌层浸润性膀胱癌(non-muscular invasive bladder cancer, NMIBC)术后患者的肿瘤复发率、不良反应及灌注前后患者生活质量的影响。方法:回顾性分析我科自2017年10月至2019年10月收治的120例诊断为膀胱癌并行经尿道膀胱肿瘤电切术(transurethral resection of bladder tumor, TURBT),且术后病理提示为高危NMIBC的患者。随机分为两组,分别为BCG、PA-MSHA交替灌注组(实验组,60例)及吉西他滨单药灌注组(对照组,60例)。术后2年不同阶段对患者进行随访,针对两组患者治疗后肿瘤复发率、不良反应及灌注前后对患者生活质量的影响进行比较分析。结果:经过术后12个月的灌注治疗,两组患者肿瘤复发率比较无统计学差异（P> 0.05）;灌注18个月及24个月,实验组肿瘤复发率（11.67%、15.00%）均低于对照组（26...     

A clinical trial of neoadjuvant hyperthermic intravesical chemotherapy (HIVEC) for treating intermediate and high-risk non-muscle invasive bladder cancer

Purpose: Ths paper reports a pilot/feasibility trial of neoadjuvant hyperthermic intravesical chemotherapy (HIVEC) prior to transurethral resection of bladder tumour (TURBT) for non-muscle invasive bladder cancer (NMIBC). Materials and methods: A pilot/feasibility clinical trial was performed and 15 patients with intermediate to high-risk NMIBC received HIVEC prior to TURBT. HIVEC consisting of eight weekly instillations of intravesical MMC (80?mg in 50?mL) delivered with the novel Combat BRS® system at a temperature of 43?°C for 60?min. Treatment-related adverse effects were measured and patients were followed for 2 years for disease recurrence. Results: A total of 119 HIVEC treatments occurred. Grade 1 adverse events consisted of irritative bladder symptoms (33%), bladder spasms (27%), pain (27%), haematuria (20%) and urinary tract infection (UTI; 14%). Grade 2 adverse events were bladder calcification (7%) and reduced bladder capacity (7%). No grade 3 or higher toxicity was observed. At TURBT, eight patients (53%) were complete responders (pT0) while seven (47%) were partial responders. With a median follow-up of 29 months, the 3-year cumulative incidence of recurrence was 15%. Conclusions: The Combat BRS® system achieved target bladder temperatures and delivered HIVEC with a favourable side-effect profile. Our pilot trial also provides preliminary evidence of treatment efficacy.     

新辅助与辅助膀胱热灌注化疗治疗高危非肌层浸润性膀胱癌的疗效对比

 目的 探讨经尿道膀胱肿瘤电切术（TURBT）术前新辅助膀胱热灌注化疗对比术后辅助膀胱热灌注化疗治疗高危非肌层浸润性膀胱癌的疗效。方法 收集经尿道膀胱肿瘤电切术术前或术后使用BR-TRG-Ⅱ型体腔热灌注治疗仪行吉西他滨膀胱热灌注化疗治疗高危非肌层浸润性膀胱癌患者40例,其中16例行术前（吉西他滨1000 mg,45℃,45 min）新辅助膀胱热灌注化疗3次,隔天一次,治疗结束后3~7天行经尿道膀胱肿瘤电切术,定义为新辅助组;另外24例患者先行TURBT手术,术后即刻或者隔天（吉西他滨1000 mg,45℃,45 min）行辅助膀胱热灌注化疗,定义为辅助组。记录并比较两组患者无疾病复发生存期（RFS）以及不良反应。结果 全部40例患者均完成3次吉西他滨膀胱热灌注化疗,新辅助组患者中,完全缓解（pT0）11例（68.8%）,部分缓解5例（31.2%）。新辅助组中位无复发生存期为54月,辅助组中位无复发生存期为45月,两者比较差异无统计学意义（P=0.3146）。两组患者不良反应可耐受。结论 无论是新辅助还是辅助治疗,使用BR-TRG-Ⅱ型体腔热灌注治疗仪行吉西他滨膀胱热灌注化疗治疗高危非肌层浸润性膀胱癌安全有效。     

Intra-Arterial Chemotherapy is Reliable in Preventing High-Risk Superficial Bladder Cancer from Recurrence and Progression

Abstract

The purpose of this prospective study was to evaluate the therapeutic effects of intra-arterial chemotherapy in preventing high-risk superficial bladder cancer from recurrence and progression. From May 2003 to December 2007, 52 patients were divided randomly into 2 groups. Twenty-five patients were given intra-arterial chemotherapy with gemcitabine and cisplatin, and 27 patients received intravesical instillation with epirubicin. After 6-67 months of follow-up (median, 40 months), the overall recurrence-free rates of the intra-arterial chemotherapy and intravesical instillation groups were 83.3% and 33.4%, respectively (p=0.001 log rank). Tumor progression was not found in the intra-arterial chemotherapy group while 7 patients in the intravesical instillation group had tumor progression. The overall tumor progression free rates were 100% and 58.5%, respectively (p=0.009 log rank). The patients with functional bladders were 100% and 81.5% in the intra-arterial chemotherapy and intravesical instillation groups after 67 months of follow-up, respectively. In conclusion, intra-arterial chemotherapy is more effective than intravesical instillation in preventing high-risk superficial bladder cancer from recurrence and progression.     

Risk-Based Assessment Of the Impact Of Intravesical Therapy on Recurrence-Free Survival Rate Following Resection of Suspected Low-grade,Non-muscle-invasive Bladder Cancer (NMIBC): A Southwest Oncology Groups (SWOG) S0337 Posthoc Analysis

BackgroundNonmuscle invasive bladder cancer (NMIBC) has an elevated risk of recurrence, and immediate postresection intravesical instillation of chemotherapy (IVC) significantly reduces the risk of recurrence. Questions remain about which subpopulation may maximally benefit from IVC. Our aim was to develop risk groups based on recurrence risk in NMIBC, and then evaluate the impact of a single, postoperative instillation of IVC on the subsequent risk of recurrence for each risk group.Material and MethodsUsing the SWOG S0337 trial cohort, we performed a posthoc analysis of 345 patients who were diagnosed with suspected low-grade NMIBC, underwent transurethral resection of the bladder tumor (TURBT), and received post-operative IVC (gemcitabine vs. saline). Using regression tree analysis, the regression tree stratified patients based on their risk of recurrence into low-risk – single tumor and aged < 57 years, intermediate-risk – single tumor and aged ≥ 57 years, and high-risk – multiple tumors. We used Cox proportional hazard models to test the impact of recurrence-free rate, and after adjustment to available covariates.ResultsMedian age of the cohort was 66.5 (IQR: 59.7-75.8 years) with 85% of patients being males. Median overall follow-up time was 3.07 years (IQR: 0.75-4.01 years). When testing the impact of treatment in each risk group separately, we found that patients in the intermediate-risk treated with gemcitabine had a 24-month recurrence free rate of 77% (95% CI: 68%-86%) vs. 59% (95% CI: 49%-70%) in the saline group. This survival difference was confirmed on multivariable analysis (hazard ratio: 0.39, 95% CI: 23%-66%, P < 0.001). This group represented 53% of our cohort. Conversely, we did not observe a significant difference in recurrence-free survival among patients in the low- (P = 0.7) and high-risk (P = 0.4) groups.ConclusionOur findings indicate that older patients with a single tumor of suspected low-grade NMIBC at TURBT maximally benefit from immediate postresection IVC (gemcitabine).