Mungan N A, Witjes J A
Department of Urology, University Hospital, Nijmegen, The Netherlands.
Br J Urol. 1998 Aug;82(2):213-23. doi: 10.1046/j.1464-410x.1998.00720.x.
The mechanisms by which BCG exerts its antitumour activity remain unclear. Attachment of BCG to the bladder via FN has been shown to be an important step in initiating its antitumorigenic activity. The mechanism(s) by which BCG operates requires LAK cells, BCG-activated killer cells, T lymphocytes (CD4) helper cells and CD8 suppressor/cytotoxic cells) and monocytes. The optimal route of administration is intravesical. The efficacy of a BCG vaccine depends on the viability, dose and strain. Differences in efficacy and side-effects have not been shown between different strains. Low-dose regimens successfully protect from recurrences, with fewer side-effects. The initial schedule of BCG is a course of six instillations in 6 weeks; when the patient fails this course, two possibilities arise. The first is maintenance therapy; response rates improve but there is more local and systemic toxicity. The second is a further 6-week course, and this seems most useful in those with a sustained response to the initial treatment. The clinical response to BCG therapy can be monitored using cytokine measurements or p53 determinations. Toxicity remains a major problem in BCG treatment and triple antituberculosis combination therapy should be given for 3 months in those with severe systemic side-effects. The use of prophylactic isoniazid is not recommend to decrease side-effects. The clinical results of BCG have been good, with success rates of 58-100%, with a minimal follow-up of one year in prophylaxis. BCG seems superior to intravesical therapy, but at the cost of inducing more adverse effects. BCG is not indicated for low- and intermediate-risk patients, in whom chemotherapy is the first choice. BCG can also be used to eliminate tumour after an incomplete TUR, or in patients who are unfit for surgery, with a 60-70% success rate. The primary and best treatment for CIS is intravesical BCG; encouraging results have been reported, with success rate of 42-83% after a minimal follow-up of one year. Although currently BCG seems to be the choice for high-risk superficial TCC, many questions remain unanswered, especially about the mechanism(s) of action, the optimal dose and clinical schedule.
卡介苗发挥其抗肿瘤活性的机制尚不清楚。卡介苗通过纤连蛋白附着于膀胱已被证明是启动其抗肿瘤活性的重要一步。卡介苗发挥作用的机制需要淋巴因子激活的杀伤细胞(LAK细胞)、卡介苗激活的杀伤细胞、T淋巴细胞(CD4辅助细胞和CD8抑制/细胞毒性细胞)和单核细胞。最佳给药途径是膀胱内给药。卡介苗疫苗的疗效取决于其活力、剂量和菌株。不同菌株之间尚未显示出疗效和副作用的差异。低剂量方案能成功预防复发,且副作用较少。卡介苗的初始给药方案是在6周内进行6次灌注;当患者对该疗程无反应时,有两种可能。第一种是维持治疗;缓解率提高,但局部和全身毒性更大。第二种是再进行一个6周的疗程,这似乎对那些对初始治疗有持续反应的患者最有用。卡介苗治疗的临床反应可以通过细胞因子测量或p53测定来监测。毒性仍然是卡介苗治疗中的一个主要问题,对于有严重全身副作用的患者,应给予三联抗结核联合治疗3个月。不建议使用预防性异烟肼来减少副作用。卡介苗的临床效果良好,预防成功率为58%至100%,最少随访一年。卡介苗似乎优于膀胱内灌注治疗,但代价是会引发更多不良反应。卡介苗不适用于低风险和中风险患者,这些患者首选化疗。卡介苗也可用于经尿道膀胱肿瘤切除术(TUR)不完全后清除肿瘤,或用于不适合手术的患者,成功率为60%至70%。原位癌(CIS)的主要和最佳治疗方法是膀胱内灌注卡介苗;已报道了令人鼓舞的结果,最少随访一年后的成功率为42%至83%。尽管目前卡介苗似乎是高危浅表性膀胱癌(TCC)的首选,但许多问题仍未得到解答,尤其是关于作用机制、最佳剂量和临床方案。