Moss J T, Kadmon D
Pharmacy Service, Department of Veterans Affairs Medical Center, Houston, TX 77030.
DICP. 1991 Dec;25(12):1355-67. doi: 10.1177/106002809102501215.
In this report, we review the evolution of bacillus Calmette-Guérin (BCG) immunotherapy as a legitimate form of treatment in superficial, nonmuscle-invasive bladder cancer. In the US, an estimated 45,000 new cases of bladder cancer are diagnosed each year and the annual death rate approaches 11,000. Approximately 70 percent of these cancers are superficial at the time of initial presentation. The treatment of superficial bladder cancer has three objectives: (1) eradication of existing disease, (2) prophylaxis against tumor recurrence, and (3) prevention of tumor progression (either muscular invasion, metastatic spread, or both). Cystectomy generally is reserved for muscle-invasive disease. Transurethral resection of the bladder tumor is the preferred initial therapy. Intravesical instillations of various chemotherapeutic agents following transurethral resection have been extensively investigated. Some of the common agents used include thiotepa, mitomycin, and doxorubicin. Despite such treatment efforts, however, over 40 percent of patients with superficial bladder cancer experience a recurrence of their tumor within three years. Approximately half of these recurrences either present as less-well-differentiated tumors or have already penetrated into the bladder musculature, metastasized, or both. Since Morales et al. first introduced intravesical BCG vaccine for prophylaxis as well as for treatment of superficial bladder tumors in 1976, support has grown rapidly for its use as an alternative to chemotherapy. When used with prophylactic intent following transurethral resection, recurrence rates are lower than those achieved with other agents. In addition, BCG is emerging as the consensus drug of choice for treating carcinoma in situ of the bladder. The mechanisms by which BCG exerts its antitumor activity remain largely unknown. BCG is thought to stimulate a localized, nonspecific inflammatory response that leads to subsequent shedding of tumor cells. A large body of clinical and experimental data suggest an association between the development of an immunologic response to BCG and successful antitumor activity. No universally accepted therapeutic regimen has been agreed upon. One regimen commonly used consists of an ampul of BCG mixed with 50 mL of NaCl 0.9%, instilled once a week for six weeks and retained for two hours prior to voiding. Maintenance therapy generally consists of intravesical doses given at three-month cycles for at least two years of recurrence-free follow-up. Because BCG is a biologic agent, the commercially available products may differ in weight, colony-forming units per vial, and antigenicity. How these product characteristics affect clinical responsiveness to different strains of BCG remains unanswered.
在本报告中，我们回顾了卡介苗（BCG）免疫疗法作为浅表性、非肌层浸润性膀胱癌一种合理治疗方式的发展历程。在美国，每年估计有45000例新发膀胱癌病例被诊断出来，年死亡率接近11000例。这些癌症中约70%在初次就诊时为浅表性。浅表性膀胱癌的治疗有三个目标：（1）根除现有疾病；（2）预防肿瘤复发；（3）预防肿瘤进展（无论是肌层浸润、转移扩散或两者皆有）。膀胱切除术通常用于肌层浸润性疾病。经尿道膀胱肿瘤切除术是首选的初始治疗方法。经尿道切除术后膀胱内灌注各种化疗药物已得到广泛研究。一些常用药物包括噻替派、丝裂霉素和阿霉素。然而，尽管进行了这些治疗，超过40%的浅表性膀胱癌患者在三年内会出现肿瘤复发。这些复发中约一半表现为分化较差的肿瘤，或者已经侵犯膀胱肌层、发生转移或两者皆有。自1976年莫拉莱斯等人首次引入膀胱内卡介苗疫苗用于预防和治疗浅表性膀胱肿瘤以来，其作为化疗替代药物的应用迅速得到支持。经尿道切除术后用于预防目的时，其复发率低于其他药物。此外，卡介苗正逐渐成为治疗膀胱原位癌的共识性首选药物。卡介苗发挥抗肿瘤活性的机制在很大程度上仍不清楚。卡介苗被认为可刺激局部非特异性炎症反应，从而导致肿瘤细胞随后脱落。大量临床和实验数据表明，对卡介苗产生免疫反应与成功的抗肿瘤活性之间存在关联。尚未达成普遍接受的治疗方案。一种常用方案是将一安瓿卡介苗与50 mL 0.9%的氯化钠混合，每周灌注一次，共六周，排尿前保留两小时。维持治疗通常包括每三个月进行一次膀胱内给药，至少进行两年无复发随访。由于卡介苗是一种生物制剂，市售产品在重量、每瓶菌落形成单位和抗原性方面可能存在差异。这些产品特性如何影响对不同卡介苗菌株的临床反应性仍未得到解答。
