膀胱内注射阿霉素与卡介苗免疫疗法治疗膀胱移行细胞癌的随机试验。

A randomized trial of intravesical doxorubicin and immunotherapy with bacille Calmette-Guérin for transitional-cell carcinoma of the bladder.

作者信息

Lamm D L, Blumenstein B A, Crawford E D, Montie J E, Scardino P, Grossman H B, Stanisic T H, Smith J A, Sullivan J, Sarosdy M F

机构信息

West Virginia University Medical Center, Morgantown.

出版信息

N Engl J Med. 1991 Oct 24;325(17):1205-9. doi: 10.1056/NEJM199110243251703.

DOI:10.1056/NEJM199110243251703

PMID:1922207

Abstract

BACKGROUND

In carcinoma of the bladder, both intravesical chemotherapy and immunotherapy can induce tumor regression and reduce the rate of recurrence, but the relative merits of these two therapies are unclear. We conducted a multi-institutional study to address this question.

METHODS

Patients with rapidly recurrent (stage Ta and T1) or in situ transitional-cell carcinoma of the bladder were randomly assigned to receive either doxorubicin administered intravesically or bacille Calmette-Guérin (BCG) administered both intravesically and percutaneously. The 262 eligible patients were followed for a median of 65 months. Complete responses to treatment of carcinoma in situ were confirmed by biopsy and cytologic analysis of the urine.

RESULTS

For patients with Ta and T1 tumors without carcinoma in situ, the estimated probability of being disease free at five years was 17 percent after doxorubicin, as compared with 37 percent after immunotherapy with BCG (P = 0.015). The median times to treatment failure (termination of treatment, due to persistence, recurrence, or progression of disease) were 10.4 and 22.5 months, respectively. For patients with carcinoma in situ the complete-response probability estimates (i.e., the estimated probability of documented disappearance of disease) were 34 percent for doxorubicin (23 of 67 patients) and 70 percent for BCG (45 of 64 patients) (P less than 0.001); the median times to treatment failure were 5.1 and 39 months, respectively. The probability of being disease-free at five years survival among the patients with carcinoma in situ was 18 percent after treatment with doxorubicin and 45 percent after BCG therapy. Patients treated with BCG had a higher incidence of toxic systemic effects and a larger number of local irritative symptoms than patients treated with doxorubicin, but few of these adverse reactions were severe.

CONCLUSIONS

As compared with intravesical doxorubicin, immunotherapy with BCG provides improved protection against the recurrence of superficial bladder cancer.

摘要

背景

在膀胱癌中，膀胱内化疗和免疫疗法均可诱导肿瘤消退并降低复发率，但这两种疗法的相对优缺点尚不清楚。我们开展了一项多机构研究以解决这一问题。

方法

将膀胱快速复发（Ta期和T1期）或原位移行细胞癌患者随机分配，分别接受膀胱内给予阿霉素或膀胱内及经皮给予卡介苗（BCG）。262例符合条件的患者中位随访65个月。原位癌治疗的完全缓解通过活检及尿液细胞学分析确认。

结果

对于无原位癌的Ta和T1期肿瘤患者，阿霉素治疗后五年无病概率估计为17%，而卡介苗免疫治疗后为37%（P = 0.015）。治疗失败（因疾病持续、复发或进展而终止治疗）的中位时间分别为10.4个月和22.5个月。对于原位癌患者，阿霉素的完全缓解概率估计值（即记录到疾病消失的估计概率）为34%（67例患者中的23例），卡介苗为70%（64例患者中的45例）（P<0.001）；治疗失败的中位时间分别为5.1个月和39个月。原位癌患者中，阿霉素治疗后五年无病生存概率为18%，卡介苗治疗后为45%。与接受阿霉素治疗的患者相比，接受卡介苗治疗的患者全身毒性作用发生率更高，局部刺激症状更多，但这些不良反应很少严重。