Randomized study of single instillation of epirubicin for superficial bladder carcinoma: long-term clinical outcomes

PURPOSE: Intravesical instillation of epirubicin (EPI) is one of the most effective adjuvant therapies for nonmuscle-invasive bladder cancer postoperation. We evaluated the long-term efficacy of single dose intravesical epirubicin for superficial bladder carcinoma recurrence. METHODS: Between June 1997 and May 1998, a total of 47 patients with resectable superficial bladder carcinoma (Ta-1, Grade 1-2), primary or recurrent with no recurrence during last one year, were enrolled in this study. All patients were randomized into 3 study groups: Group A-single epirubicin (80 mg/40 mL of normal saline) was administered into the bladder within 6 hours postoperation; Group B-40 mg Epirubicin consecutively; Group C-40 mg mitomycin C, consecutively. In Group B and C, instillation were given every week for 6- 8 weeks and then every one month for 10 months. Patients were followed up at 3, 6, 9, 12, 18, 24, 36, 48, and 60 months of treatment. The analyzed background factors were the therapeutic method, tumor recurrence, and side effects. RESULTS: Of the 47 patients, 43 (91.5 percent) were eligible and were followed up for 5 years postoperation. The disease free intervals of the three groups were found to have no significant differences (F = 10.28, p > 0.05). The recurrence rates were 35.7 percent (5/14), 33.3 percent (5/15), and 40 percent (6/15), respectively (chi(2)= 0.83, p > 0.05). Side effects of group A (13.6 percent) was lower than that of Group B or C (53.3 percent and 46.7 percent, respectively) significantly (chi(2) test, p < 0.01). CONCLUSIONS: These data indicate that single dose of epirubicin instillation postoperation can reduce the recurrence of superficial bladder carcinoma and has low side effects.     

吡柔比星(THP)膀胱灌注预防膀胱癌术后复发的疗效观察

目的;分析１９９８年６月－１９９９年８月间２２例浅表性膀胱癌患者行膀胱部分切除术或行ＴＵＲ－Ｂｔ及电灼术后采用吡柔比星膀胱灌注预防肿瘤复发。方法：ＴＨＰ３０ｍｇ,每周一次,连用８周,而后每月１次,连用８个月。结果：总疗程１０个月,平均随访９．７个月,复发率１３．６％。结论：ＴＨＰ用于临床,效果好,不良反应少,给药方便,值得临床推广应用。     

吡柔比星膀胱灌注预防膀胱癌术后复发临床观察

目的:分析2002年6月~2005年8月间158例浅表性膀胱癌患者行膀胱部分切除术或行TUR-Bt术后采用吡柔比星(THP)膀胱灌注预防肿瘤复发。方法:THP30mg,每周1次,连用8周,而后每月1次,连用10个月,总疗程12个月。结果:所有患者均获6~24个月的随访。平均随访12.3个月。复发20例,复发率12.8%。结论:THP用于膀胱灌注预防膀胱癌术后复发有较好的疗效,不良反应少,给药方便,值得临床推广应用。     

膀胱癌术后吡柔比星膀胱灌注预防复发的临床观察

目的:探讨膀胱癌术后吡柔比星(THP)膀胱灌注预防复发的临床疗效。方法:将90例浅表性膀胱癌术后患者随机分为A、B、C 3组,每组30例,其中A组行膀胱灌注吡柔比星治疗,30 mg/次,1次/周,共治疗8次。B组也行膀胱灌注吡柔比星治疗,且前8周治疗与A组相同,之后改为每月灌注1次,30 mg/次,连用10个月,总周期12个月。C组行膀胱灌注卡介苗(BCG)治疗,80 mg/次,1次/周,以后逐渐减少治疗次数,总周期12个月。比较3组患者的不良反应以及复发率。结果:3组患者均随访2年,其中A、B、C 3组患者1年后的复发率分别为10.0%(3/30)、6.7%(2/30)和6.7%(2/30),差异无统计学意义(χ2=1.8,P>0.05)。3组患者2年后的复发率分别为16.7%(5/30)、13.3%(4/30)和9.0%(3/30),其中A组与C组差异有统计学意义(χ2=9.2,P<0.05)。3组不良反应发生率分别为10.0%(3/30)、20.0%(6/30)和36.7%(11/30),A、B两组的不良反应少于C组(χ2=11.8,P<0.05)。结论:THP用于膀胱灌注预防膀胱癌术后复发,短期与长期疗效相比无统计学差异,且长期疗效与BCG疗效相比无统计学差异,但不良反应较少,可根据患者的具体情况用药。     

Postoperative prophylactic intravesical instillation of tetrahydropyranyl-adriamycin (THP) for superficial bladder cancer

Intravesical instillation of tetrahydropyranyl-adriamycin (THP) was performed on 51 patients with superficial bladder cancer after transurethral resection (TUR) for prophylaxis of recurrence. The instillation was carried out with 20 mg of THP dissolved in 40 ml of distilled normal saline. Instillation was performed once 24 hours postoperatively, 9 times every 2 weeks, and 8 times every 4 weeks. These drugs were instilled for 30 to 60 minutes. The recurrence-free survival at 1, 2 and 3 years was 74.5%, 64.6% and 58.0%, respectively. Side effects of THP instillation were observed in only 4 cases (7.8%) as slight urinary frequency or micturition pain. Cases involving 5 or more tumors, or tumors measuring 3 cm or larger, more frequently demonstrated recurrence. The cases that did not respond to preoperative intravesical instillation of THP demonstrated a high frequency of recurrence. Intravesical instillation of THP as a prophylaxis against recurrence of superficial bladder cancer was effective in selected patients.     

吡柔比星膀胱灌注预防膀胱癌术后复发临床观察

目的分析2006年6月至2009年10月间68例浅表性膀胱癌患者行膀胱部分切除术或行TUR-Bt术后采用吡柔比星（THP）膀胱灌注预防肿瘤复发的疗效。方法 THP30 mg,每周1次,连用8周,而后每月1次,连用10个月,总疗程12个月。结果所有患者均获6～30个月的随访。平均随访12.1个月。复发9例,复发率13.1%。结论 THP用于膀胱灌注预防膀胱癌术后复发有较好的疗效,不良反应少,给药方便,值得临床推广应用。     

Intravesical instillation of doxorubicin or epirubicin for chemoprophylaxis of superficial bladder cancer--the fifth study of the Japanese Urological Cancer Research Group for Adriamycin/Farumorubicin

A total of 465 patients with primary and multiple or recurrent, stages Ta and T1 superficial bladder cancer were included in this randomized multicenter trial to compare the prophylactic effect by 17 times instillation of 40 mg doxorubicin or 40 mg epirubicin with no instillation after transurethral resection of tumor(s). The primary endpoint was first recurrence after transurethral resection. Endoscopic examination as well as urinary cytology was performed in each case every three months. It became evident that the recurrence rate in the doxorubicin or epirubicin instillation arm was lower that in the no instillation arm. Toxicity was mainly restricted to bladder irritation in about 10% of patients in each instillation arm.     

α-干扰素加吡柔比星灌注化疗对预防膀胱癌术后复发的疗效

背景与目的浅表性膀胱移行细胞癌术后易复发,本研究旨在探讨α-干扰素(interferon-alpha,IFN-α)联合吡柔比星灌注在降低浅表性膀胱癌术后复发方面的价值。方法应用重组人干扰素和吡柔比星(pirarubicin,THP)进行临床前瞻性试验研究。68例膀胱癌患者术后一周随机数字法分为两组(1)IFN-α+THP组33例,IFN-α3000万IU+THP40mg+5%GS40ml膀胱灌注;(2)THP组35例,THP40mg+5%GS40ml膀胱灌注。每周1次,连续8次,以后每月1次,共10次,12个月为一个疗程。结果随访期为6～32个月(中位随访期18.5个月),每3个月行膀胱镜检和组织活检一次。IFN-α+THP组33例患者中复发4例(12.1%),有4例出现膀胱刺激症状,3例有疲倦症状,1例出现皮疹。THP组复发8例(22.8%),有5例出现膀胱刺激症状,疲倦者3例,两组的不良反应发生率无显著性差异(P>0.05)。IFN-α+THP组比单用THP组有更好的疗效(P<0.05),尤其在预防G2、PT1膀胱肿瘤术后复发的效果优于单用THP组。结论IFN-α加THP灌注化疗对预防膀胱癌术后复发的疗效可能优于单用THP,但是其副作用情况以及是否适宜广泛使用还需作进一步的研究。     

膀胱内灌注吡柔比星预防膀胱癌术后复发的临床研究

目的研究吡柔比星膀胱灌注预防膀胱癌术后复发的疗效。方法自2002年1月至2004年12月对56例膀胱癌患者在经尿道膀胱癌电切术或膀胱部分切除术后,定期膀胱内灌注吡柔比星。每次用30mg,膀胱内保留半小时,术后第1周开始使用,每周1次,共6次;以后每2周1次,共6次;再以后每月1次,共2年。结果56例患者均随访观察2年以上,无肿瘤复发46例(82.2%),复发10例(17.9%),无全身毒副作用。结论吡柔比星膀胱内灌注预防膀胱癌术后复发疗效肯定,毒副作用小。     

吡柔比星联合聚维酮膀胱灌注预防浅表膀胱癌复发

背景与目的：膀胱癌术后易复发,且可恶性进展,影响预后,如何预防其复发一直为学者们所关注,本研究探讨吡柔比星（pirarubicin,THP)联合聚维酮（polyvinylpyrrolidone,PVP)膀胱灌注预防浅表膀胱癌复发的疗效及副作用。方法：1999年10月－2002年5月,选择34例浅表膀胱癌术后患者,将20mg THP溶解于10ml生理盐水和20ml PVP中,然后经导尿管注入膀胱并保留1小时,结果：所有患者随访5－26个月,平均随访17．2个月,2例复发,复发率5．8％,4例血尿,膀胱刺激症6例（17．6％）,结论：THP联合PVP膀胱灌注预防浅表膀胱癌复发疗效确切,副作用少。     

Randomized study of single early instillation of (2"R)-4'-O-tetrahydropyranyl-doxorubicin for a single superficial bladder carcinoma

BACKGROUND: Although transurethral resection of a bladder tumor (TUR-Bt) alone has been standard treatment for single superficial bladder carcinoma, some authors reported a certain prophylactic effect of a single immediate intravesical instillation of chemotherapeutic agent after TUR-Bt. A prospective randomized study was conducted to determine whether a single (2"R)-4'-O-tetrahydropyranyl-doxorubicin (THP) instillation immediately after TUR-Bt is beneficial to patients with a single superficial bladder carcinoma. METHODS: One hundred seventy patients with a single resectable superficial bladder carcinoma (Ta-1, primary or recurrent with no recurrence during the last 1 year) were enrolled in this study. THP (30 mg/30 mL of normal saline) was administered into the bladder within 6 hours after TUR-Bt in arm A, while TUR-Bt alone was done in arm B. RESULTS: Of the 170 patients, 160 (94.1%) were eligible and were followed up for a median time of 40.8 months. There was a significant difference in the recurrence free curve between the 2 arms (log-rank test; P = 0.0026), with 92.4% recurrence free rate at 1 year, 82.7% at 2 years, and 78.8% at 3 years in arm A (84 patients) and 67.0%, 55.7%, and 52.6%, respectively, in arm B. The recurrence rate per year was 0.11 +/- 0.22 in arm A and 0.24 +/- 0.36 in arm B, with a significant difference (P = 0.007). Toxicity included pain with micturition in 9 patients (10.7%), urinary frequency/urgency in 5 patients (6.0%), and macroscopic hematuria in 7 patients (8.3%). CONCLUSIONS: These data indicate that a single THP instillation immediately after TUR reduces the recurrence of superficial bladder carcinoma.     

33例膀胱内灌注吡柔比星预防浅表性膀胱癌术后复发疗效观察

目的评价吡柔比星(THP)膀胱内灌注预防浅表性膀胱癌术后复发的近期疗效和不良反应。方法对33例浅表性膀胱癌患者行经尿道膀胱肿瘤电切术(TURBT),术后2周THP30mg膀胱灌注,每周1次,共8次;以后每月1次,共10个月,随访期间内行膀胱镜检查。结果30例可评价疗效,无肿瘤复发28例,复发2例,复发率为6.7%;发生不良反应者12例(40.0%),均为不同程度膀胱刺激症状。结论THP膀胱内灌注预防浅表性膀胱癌术后复发近期疗效满意,不良反应小,耐受性良好。     

榄香烯与BCG膀胱灌注预防浅表性膀胱癌术后复发的临床观察

通过临床应用榄香烯膀胱内灌注,观察榄香烯预防浅表性膀胱癌术后复发的效果及毒副反应。对108例膀胱癌术后的患者,随机分为两组,分别采用榄香烯注射液及卡介苗(BCG)于术后行膀胱内灌注,榄香烯治疗组63例,BCG组45例,观察各组肿瘤复发情况、毒副反应。榄香烯组平均随访19·7个月,复发5例,复发率为7·94%;BCG组平均随访14·4个月,复发7例,复发率为15·6%。经检验,两组之间术后复发率相比较差异有统计学意义,P=0·018。初步研究结果提示,膀胱内灌注榄香烯注射液对浅表性膀胱癌预防术后复发有良好疗效,是一种值得推广新方法。     

Postoperative intravesical instillation of THP for superficial bladder tumor: clinical results of prophylactic effects on the recurrence. Fukushima THP Research Group]

Intravesical instillation of pirarubicin (THP) was performed on 66 patients with superficial bladder cancer after transurethral resection to evaluate the prophylactic effect against tumor recurrence. Intravesical chemotherapy was carried out at the concentration of 20mg/40ml. THP was initially instilled three times for one week, following instillation of every two weeks for ten times, and then every one month for seven times. Bladder irritability was demonstrated 21 of 66 cases (31.8%). Although there was a case of contracted bladder, generalized side effect was no case. Eligible cases for evaluation of efficacy were 43 out of 66 patients. The non-recurrence rate (by Kaplan-Meier's method) at one and two years were 90.4% and 77.8%, respectively. Intravesical THP instillation seems to be effective for the purpose of prophylaxis against the recurrence of superficial bladder tumor.     

经尿道电气化术加灌注化疗治疗多发膀胱肿瘤42例报告

目的探讨经尿道膀胱肿瘤电气化术结合灌注化疗治疗多发性膀胱肿瘤的方法及疗效。方法应用经尿道电气化术切除多发性膀胱肿瘤42例。术后第1周开始用丝裂霉素C（MCC）20mg灌注膀胱,每周1次,共6次,然后每4周1次,持续1年以上。结果手术时间平均45min,未发生大出血及膀胱穿孔。平均随访16个月,术后复发9例,复发率21．4％。结论经尿道膀胱肿瘤电气化术结合灌注化疗治疗多发性膀胱肿瘤是一种有效的方法。     

Antibacterial activity of adriamycin against bacillus Calmette-Guerin

Although intravesical instillation of bacillus Calmette-Guerin (BCG) or adriamycin (ADR) is an established and effective therapy for superficial bladder cancer, the current major problems are BCG-resistant and ADR-resistant bladder cancer and recurrence after the instillation therapy. Combination therapy with BCG and ADR might overcome the drug-resistance of bladder cancer. However, before combined used of BCG and ADR, it should be clarified whether ADR has bactericidal and bacteriostatic effects on BCG or not, since only alive BCG has a potential antitumor effect. In the current study, the in vitro antibacterial activity of ADR was assessed on BCG by the standard serial two-fold dilution method. When BCG was treated with ADR at 0.13-125 mu g/ml for two hours, ADR had no effect on the viability and the growth of BCG. However, ADR at 250-1,000 mu g/ml had a bactericidal effect on BCG. Epirubicin (EPI) at 0.13-15.6 mu g/ml did not affect the viability and the growth of BCG, however, EPI at 31.3-1,000 mu g/ml had a bactericidal activity. Pirarubicin (THP) at 125-1,000 mu g/ml also had a bactericidal activity. The minimal inhibitory concentrations of ADR, EPI and THP were 250, 250 and 125 mu g/ml, respectively. This study demonstrates that ADR at high concentrations had bactericidal and bacteriostatic effects on BCG. These findings suggest that combination treatment with BCG and low dose ADR could be used and overcome the resistance of bladder cancer to BCG and ADR. The possible clinical implications of the combined use of BCG and ADR are discussed.     

羟基喜树碱术后即刻灌注联合维持灌注预防非浸润性膀胱癌复发的长期疗效分析

  目的  总结大剂量羟基喜树碱即刻灌注联合维持灌注预防非肌层浸润性膀胱癌术后复发的疗效。  方法  回顾性分析了167例中、高危非肌层浸润性膀胱尿路上皮癌患者的临床资料.男性116例, 女性51例, 平均年龄51岁。所有患者均经病理诊断证实, 分期为Ta71例、T₁96例, 分级为G₁66例、G₂50例、G₃51例。患者行经尿道膀胱肿瘤电切术后即刻膀胱内灌注羟基喜树碱40mg, 保留20~30 min, 术后1w开始羟基喜树碱维持灌注, 40 mg/次, 1次/w×8次, 以后1次/月×10次, 每次维持2 h。  结果  155例患者获得随访, 平均随访期92(72~112)个月。患者1、2和5年肿瘤复发率分别为23.2%、31.6%和41.3%。治疗的长期预后因素包括肿瘤的分级、分期、数目和大小。本组中膀胱Ⅰ、Ⅱ和Ⅲ度不良反应的发生率为13.5%、3.2%和1.9%, 未见Ⅳ度不良反应。全身不良反应仅见Ⅰ度不良反应, 发生率为1.3%。  结论  大剂量羟基喜树碱即刻灌注联合维持灌注预防膀胱癌术后复发的长期疗效较为满意, 不良反应发生率低, 患者多能良好耐受治疗。      

膀胱内灌注血卟啉衍生物加抗坏血酸全膀胱激光照射预防膀胱癌…

目的 探讨预防膀胱癌术后复发的新疗法,评价经膀胱内灌注血卟啉衍生物加抗坏血酸行激光全膀胱照射的光动力疗法预防复发的疗效。方法 采用经膀胱内灌注血卟啉衍生物癌光啉（ＰｓＤ－００７）加抗坏血酸行全膀胱激光照射方法,治疗３０例膀胱癌术后患者。结果 ３０例患者随诊３０个月,其肿瘤复发率为２３．３％（７／３０）。无一例发生膀胱挛缩以及皮肤光毒副反应。结论 用膀胱内灌注血卟啉衍生物加抗坏血酸全膀胱照射能有效地     

丝裂霉素C加透明质酸酶膀胱灌注预防膀胱癌复发的疗效观察

 目的观察丝裂霉素C加透明质酸酶膀胱内灌注预防膀胱癌复发的疗效。方法88例膀胱癌患者随机分为两组丝裂霉素C加透明质酸酶组46例,在肿瘤切除术后应用丝裂霉素C20mg加透明质酸酶3000U定期膀胱内灌注。对照组42例,术后单纯应用丝裂霉素C20mg定期膀胱内灌注。观察两组肿瘤复发情况。结果经随访12～36个月,平均24.5个月,丝裂霉素C加透明质酸酶组肿瘤复发率为10.9%,单纯丝裂霉素C组肿瘤复发率为31.0%,两组比较,差异有显著性(P<0.05)。结论丝裂霉素C加透明质酸酶膀胱内灌注能更有效地预防膀胱癌的术后复发。     

A multicenter prospective phase II randomized trial of epirubicin/vinorelbine versus pegylated liposomal doxorubicin/vinorelbine as first-line treatment in advanced breast cancer. A GOIM study

Background

To evaluate activity and tolerability of two anthracycline-containing regimens as first-line treatment for anthracycline-naïve relapsed breast cancer patients.

Methods

Patients with relapsed breast cancer not previously treated with adjuvant anthracyclines were randomly assigned to epirubicin/vinorelbine (arm A: EPI/VNB, EPI 90 mg/m² on day 1, VNB 25 mg/m² on days 1,5 plus G-CSF subcutaneously on days 7-12, with cycles repeated every 21 days), or to pegylated liposomal doxorubicin/VNB (arm B: PLD/VNB, PLD 40 mg/m² on day 1, VNB 30 mg/m² on days 1, 15, with cycles repeated every 4 weeks). Primary objective was to evaluate the efficacy of the two regimens in terms of response rate, secondarily toxicity, progression free survival and overall survival.

Results

One hundred and four patients have been enrolled (arm A 54, arm B 50): characteristics were well balanced between the 2 arms. Responses were as follows: arm A, 3 (5.6%) CR, 20 (37%) PR, (ORR 42.6%, 95%CI 29.3%-55.9%); arm B, 8 (16%) CR, 18 (36%) PR, (ORR 52%, 95%CI 38.2%-65.8%). Median progression free survival was 10.7 months in arm A (95% CI, 8.7-12.6), and 8.8 months in arm B (95% CI, 7.1-10.5). Median overall survival was 34.6 months in arm A (95%CI, 19.5-49.8) and 24.8 months in arm B (95%CI, 15.7-33.9). As toxicity concerns, both treatment regimens were well tolerated; myelosuppression was the dose-limiting toxicity, with G3-4 neutropenia occurring in 18.5% and 22% of the patients of arm A and B, respectively. No relevant differences in main toxic effects have been observed between the two arms, except for alopecia, more common in arm A, and cutaneous toxicity, observed only in arm B. No clinical congestive heart failures have been observed, one case of tachyarrhythmia was reported after the last EPI/VNB cycle, and two reversible ≥ 20% LVEF decreases have been observed in arm A.

Conclusions

Both anthracycline- containing regimens evaluated in the present study seem to be active and with a satisfactory tolerability in anthracycline-naïve relapsed breast cancer patients.