Sequential BCG and electromotive mitomycin versus BCG alone for high-risk superficial bladder cancer: a randomised controlled trial
Sequential BCG and electromotive mitomycin versus BCG alone for high-risk superficial bladder cancer: a randomised controlled trial
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DOI：
10.1016/s1470-2045(05)70472-1
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发表时间：
2006-01-01
期刊：
影响因子：
51.1
通讯作者：
Stephen, RL
中科院分区：
文献类型：
--
作者：
Di Stasi, SM;Giannantoni, A;Stephen, RL
背景 联合抗癌药物的基本原理尚未一致地应用于使用膀胱内药物治疗浅表性膀胱癌，免疫治疗卡介苗和化疗丝裂霉素似乎是一种潜在有效的组合。我们的目的是对 pT1 期膀胱癌患者单独使用卡介苗与序贯卡介苗和电动丝裂霉素进行前瞻性、随机比较。 方法 在经尿道切除和多次活检后，212 名 pT1 期膀胱癌患者被随机分配至：每周一次，每次 120 分钟输注 81 毫克卡介苗，持续 6 周 (n=105)；或每周输注81mg卡介苗，每次120分钟，持续2周，然后每周输注40mg电动丝裂霉素（膀胱内电流20mA，持续30分钟），每周一次，一个周期，共三个周期（n=107）。完全缓解者接受维持治疗：单用卡介苗，每月一次输注81 mg卡介苗，持续10个月；卡介苗和丝裂霉素联合输注，每月一次40毫克电动丝裂霉素，持续2个月，随后每月一次81毫克卡介苗，为一个周期，共三个周期。主要终点是无病间隔；次要终点是进展时间；总体生存率；和疾病特异性生存率。分析是按意向治疗进行的。该试验已在美国国家癌症研究所网站 http://clinicaltrials.gov 提交注册申请。调查结果中位随访时间为 88 个月（IQR 63-110）。序贯接受 BCG 和电动丝裂霉素治疗的患者比单独接受 BCG 治疗的患者有更高的无病间隔（69 个月 [95% Cl 55-86] vs 21 个月 [15-54]；组间差异 48 个月 [42-54]，对数秩 p=0(.)0012）。序贯接受 BCG 和电动丝裂霉素治疗的患者复发率也较低（4(.)19% [32(.)7-51(.)5] vs 57(.)9% [48(.)7-67(.)5]；组间差异为 16(.)0% [2(.)7-29(.)3]，对数秩 p=0(.)0012）；进展（9(.)3% [3(.)8-14(.)8] vs 21.9% [17(.)9-25(.)9] 组间差异 12(.)6% [3(.)0-22(.)2]，对数秩 p=0(.)004）；总死亡率（21(.)5% [13(.)5-29(.)5] vs 32(.)4% [23(.)4-41(.)4]，组间差异 10(.)9% [0(.)6-21(.)2]，对数秩 p=0(.)045）；和疾病特异性死亡率（5(.)6% [1(.)2-10(.)0] vs 16(.)2% [6(.)1-23(.)3]，组间差异 10(.)6% [2(.)5-18(.)7]，对数秩 p=0(.)01）。副作用主要集中在膀胱。解读卡介苗引起的炎症可能会增加膀胱粘膜的通透性，使丝裂霉素更容易到达靶组织，发挥抗癌作用。
Background The rationale for combining anticancer drugs has not been applied consistently to use of intravesical agents for treatment of superficial bladder cancer, for which immunotherapeutic BCG and chemotherapeutic mitomycin seem to be a potentially effective combination. We aimed to do a prospective, randomised comparison of BCG alone with that of sequential BCG and electromotive mitomycin in patients with stage pT1 bladder cancer.Methods After transurethral resection and multiple biopsies, 212 patients with stage pT1 bladder cancer were randomly assigned to: 81 mg BCG infused over 120 min once a week for 6 weeks (n=105); or to 81 mg BCG infused over 120 min once a week for 2 weeks, followed by 40 mg electromotive mitomycin (intravesical electric current 20 mA for 30 min) once a week as one cycle for three cycles (n=107). Complete responders underwent maintenance treatment: those assigned BCG alone had one infusion of 81 mg BCG once a month for 10 months, and those assigned BCG and mitomycin had 40 mg electromotive mitomycin once a month for 2 months, followed by 81 mg BCG once a month as one cycle for three cycles. The primary endpoint was disease-free interval; secondary endpoints were time to progression; overall survival; and disease-specific survival. Analyses were done by intention to treat. This trial has been submitted for registration at the US National Cancer Institute website http://clinicaltrials.gov.Findings Median follow-up was 88 months (IQR 63-110). Patients assigned sequential BCG and electromotive mitomycin had higher disease-free interval than did those assigned BCG alone (69 months [95% Cl 55-86] vs 21 months [15-54]; difference between groups 48 months [42-54], log-rank p=0(.)0012). Patients assigned sequential BCG and electromotive mitomycin also had lower recurrence (4(.)19% [32(.)7-51(.)5] vs 57(.)9% [48(.)7-67(.)5]; difference between groups 16(.)0% [2(.)7-29(.)3], log-rank p=0(.)0012); progression (9(.)3% [3(.)8-14(.)8] vs 21.9% [17(.)9-25(.)9] difference between groups 12(.)6% [3(.)0-22(.)2], log-rank p=0(.)004); overall mortality (21(.)5% [13(.)5-29(.)5] vs 32(.)4% [23(.)4-41(.)4], difference between groups 10(.)9% [0(.)6-21(.)2], log-rank p=0(.)045); and disease-specific mortality (5(.)6% [1(.)2-10(.)0] vs 16(.)2% [6(.)1-23(.)3], difference between groups 10(.)6% [2(.)5-18(.)7], log-rank p=0(.)01). Side-effects were mainly localised to the bladder.Interpretation BCG-induced inflammation might increase the permeability of the bladder mucosa such that mitomycin can reach the target tissue more easily and exert its anticancer effect.