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。     

吡柔比星联合白细胞介素Ⅱ膀胱灌注预防浅表膀胱癌复发的初步研究

目的探讨吡柔比星(THP)联合白细胞介素Ⅱ(IL-2)预防浅表膀胱癌术后复发的近期疗效.方法对37例浅表性膀胱癌患者行经尿道膀胱肿瘤电切术(TURBt)或膀胱部分切除术,术后定期用THP 30 mg IL-2 100 000 U/40 ml做膀胱内灌注,每周1次,共8次;以后每月1次,共1年,每次药物在膀胱内保留40 min,随访结果与以往应用丝裂霉素C(MMC)的病例进行比较和讨论.结果随访10～24个月,7例复发,无瘤率为81.1%(30/37).THP IL-2组与MMC组(40 mg)相比差异无显著性(P>0.05).结论 THP联合IL-2用于临床膀胱灌注预防浅表膀胱癌术后复发效果好,不良反应少,给药方便,值得临床推广应用.     

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。     

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。     

吡柔比星膀胱灌注预防膀胱癌术后复发临床观察

目的:比较吡柔比星(pirarubicin,THP)和丝裂霉素(mitomycin,MMC) 对表浅性膀胱癌术后复发的预防和不良反应。方法:将82例患者随机分为两组,Ⅰ组采用THP方案(42例),Ⅱ组采用MMC方案(40例)。分别于术后1 周开始规律膀胱灌注。比较两组复发率及药物的不良反应。结果:所有患者均随访2 年以上。Ⅰ组复发率为4.8%(2/42),Ⅱ组复发率20.0%(8/40)。两组比较差异有显著性（P＜0.05）。而THP组不良反应发生率明显低于MMC组（P＜0.05）。结论:THP膀胱灌注对膀胱癌保留膀胱术后防止复发疗效满意,不良反应轻,耐受性好且安全。     

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。     

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。     

Short-duration bladder instillation therapy with pirarubicin for superficial bladder tumor based on pharmacodynamic study]

From our experimental study, an instillation of THP for 5 minutes was attempted in 23 patients with superficial bladder tumors. THP (30 mg dissolved in 50 ml of distilled water) was instilled into the bladder 6 times every 48 hours. Of 23 patients, 9 (39%) showed complete disappearance of the bladder tumors, while partial disappearance (more than 50% tumor reduction) was observed in 3 cases (13%). Therefore the overall response rate was 52%. Neither urinary frequency nor hematuria was observed in all the cases, while painful urination was observed in 3 cases (13%). This newly designed bladder instillation therapy was effective against superficial bladder tumors with low incidence of local side effects.     

The study on intravesical instillation of THP in the treatment of in-situ and superficial bladder cancers]

The efficacy and safety of Pirarubicin (THP), administered by intravesical instillation, have been studied in recurrent multiple superficial bladder cancer patients and patients who tested positive by urine cytology but lacked protuberant legions (CIS). The average age and range of the 19 patients (M 15, F4) studied were 63.3 (37-84). Twelve patients had protuberant, multiple cancer and 7 patients had CIS. Sixteen of the cases were recurrent disease. Twenty mg THP, delufed in 40 ml of 5% glucose solution were instilled for 2 hours once or twice a week. Each patients received 8 treatments. One week after the last treatment, the therapeutic result was evaluated on the bases of cystoscopy and urine cytology. Before and after administration, CBC and biochemical blood tests were run. Nine of the 12 patients (75%) with multiple recurrent tumor and all the 7 patients with CIS showed complete response. The total outcome for CR was 84.2% in this study. Intravesical instillation with THP did not cause any serious side effects.     

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。     

Intravesical BCG therapy in patients with recurrent superficial bladder tumors

Intravesical instillation of BCG has recently become a treatment for superficial bladder tumor, and favorable results are reported. We have also obtained favorable results by performing intravesical BCG therapy to totally 32 cases of superficial recurrent bladder tumor and carcinoma in situ (CIS) one indicated for total cystectomy. The subjects were 29 cases of Ta and T1 and 4 cases of Tis, which are classified into 27 cases for treatment and 5 cases for prevention of recurrence after TUR. As the method for administration, 120 or 80 mg of BCG was dissolved in physiological saline and infused intravesically every week a total of 8 times. As a result of designating the patients who received the treatment more than 4 times as the subject, CR and PR were 19 cases (73%) and 5 cases (19%), or respectively, out of 26 assessable cases, and effective rate including PR was 93%. No recurrence has been observed so far in any of 5 cases treated for prevention of recurrence. Side effects which required treatment were observed in 13 cases (41%), but treatment could be continued by symptomatic therapy in most of the cases. Treatment was discontinued in 4 cases, 3 of which were hepatic disorders. It is considered that intravesical instillation of BCG is a therapeutic procedure which is good for trial in future in the light of the great efficacy obtained in the present study.     

Phase II collaborative study of (2'R)-4'-0-tetrahydropyranyladriamycin (THP) for urological malignancies--Urological Co-operative THP Study Group

A Phase II clinical trial of a new anthracycline, (2'R)-4'-0-tetrahydropyranyladriamycin (THP), was performed in 137 patients with urological malignancies. Out of them, 111 patients were evaluated for tumor responses and 125 patients were evaluated for adverse effects. In cases of intravenous administration, overall response rate was 18.5% (22.2% for bladder cancer, 30.0% for tumors of the renal pelvis and ureter, and 6.7% for prostatic cancer). In the case of intra-arterial administration, overall response rate was 42.9% (50.0% for bladder cancer). For 50 patients with superficial bladder cancer intravesical chemotherapy with THP was performed. Sixteen patients showed complete disappearance of the tumor, 2 patients showed more than 90% tumor regression and 12 patients showed more than 50% tumor regression, respectively. Overall response rate was 60%. Cardiotoxicity was minimal. Alopecia was noted in a total of 16 patients, but this was minimal. Leukocytopenia was the major adverse effect among patients undergoing systemic THP administration. In conclusion, THP was most effective against transitional cell carcinoma of the urinary tract.     

吡柔比星与卡介苗世丝裂霉素膀胱灌注治疗浅表性膀胱癌的疗效对比观察

目的评价吡柔比星(THP)、卡介苗(BCG)、丝裂霉素(MMC)三种药物膀胱灌注治疗浅表性膀胱癌的不同疗效。方法将200例浅表性膀胱癌随机分为3组,分别用THP、BCG、MMC作膀胱灌注治疗药物,观察其不同疗效。结果所有病例随访3～24个月,平均14个月。THP组复发6(6/72)例,BCG组复发6(6/68)例,MMC组复发10(10/60)例。结论吡柔比星疗效与卡介苗相似,稍优于卡介苗。卡介苗疗效优于丝裂霉素。丝裂霉素耐受性最好。吡柔比星不良反应小,耐受性好,可作为临床一线用药。     

147例表浅性膀胱癌预后因素分析

目的 :探讨表浅性膀胱癌各种因素与患者预后的关系。方法 :对 147例表浅性膀胱癌进行回顾性分析。结果 :147例中 ,72例术后复发 ( 4 9% ) ,术后 5年复发率为 35.4 %。初诊时为多发者、直径大于 3cm、分级与分期高的肿瘤术后复发率分别高于单发者、直径小于 3cm者、分级、分期低的肿瘤。术后 6个月内肿瘤复发者经治疗后肿瘤再次复发的机会高 ,术后膀胱内灌药可以预防肿瘤复发。结论 :肿瘤分级与分期高、多发肿瘤、直径大于 3cm者及术后膀胱内未灌药者复发率高     

Intravesical chemotherapy for superficial bladder tumors

Intravesical chemotherapy is one of the most effective treatments for superficial bladder tumors. Recent progress in the development of chemotherapeutic agents has provided a variety of compounds of potential benefit for intravesical administration in cases of superficial bladder tumors, including thio-TEPA, MMC, carboquone, adriamycin, FT-207, cytosine arabinoside and bleomycin, and the in therapeutic effectiveness has been reported. We selected adriamycin, because it is considered suitable for intravesical instillation. A 68% effectiveness has been experienced for instillation repeated six to nine times (adriamycin 50 mg/normal saline 30 ml) and side effects occurred in 23% of patients. Intravesical chemotherapy has also been attempted to prevent recurrence after conservative therapy but these modalities still seem to need further study.     

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.     

Intravesical chemotherapy of (2'R)-4'-O-tetrahydropyranyladriamycin in bladder tumor

The effect of (2"R)-4'-0-tetrahydropyranyladriamycin (THP), a derivative of adriamycin (ADM) on bladder tumors was evaluated by intravesical instillation. Twenty-one patients with bladder tumors were treated with THP instillation into the bladder. THP (20-30 mg dissolved in 20-40 ml of distilled water) was instilled into the bladder daily for 3 consecutive days as a course. The patients received 2 to 5 courses in total. Of 21 patients, 4 showed complete disappearance of the bladder tumors, while partial response (50% tumor reduction) was observed in 6 cases. Therefore, the overall response rate was 48%. However, with regard to the 16 patients with superficial bladder tumors (Ta, T1) an overall response rate of 63% was noted. The main side effect of THP instillation was temporary bladder irritability, which was seen in 57% of all the patients. No cases revealed systemic side effects. The same antitumor effect was obtained at a lower concentration of THP in the intravesical chemotherapy, compared with that of ADM. It was concluded that THP is a useful drug for the intravesical chemotherapy of bladder tumors.     

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。