Sarosdy M F, Manyak M J, Sagalowsky A I, Belldegrun A, Benson M C, Bihrle W, Carroll P R, Ellis W J, Hudson M A, Sharkey F E
Department of Urology, University of Texas Health Science Center, San Antonio, USA.
Urology. 1998 Feb;51(2):226-31. doi: 10.1016/s0090-4295(97)00510-4.
Bropirimine is an oral immunomodulator that has demonstrated anticancer activity in transitional cell carcinoma in situ (CIS) in both the bladder and upper urinary tract. Activity also has been documented in patients after prior therapy with bacille Calmette-Guérin (BCG). To more accurately estimate bropirimine's efficacy in BCG-resistant bladder CIS, a Phase II trial was performed. A separate analysis was performed in additional patients intolerant of BCG toxicity.
Patients received bropirimine 3.0 g/day by mouth for 3 consecutive days, weekly, for up to 1 year. Bladder biopsies and cytologic examination were performed quarterly. Complete response (CR) required negative biopsy and cytology results.
Twenty-one of 86 patients entered were not evaluable. CR was seen in 21 (32%; 95th percentile confidence interval [CI], 21% to 44%) of 65 evaluable patients, including 14 (30%, CI 17% to 43%) of 47 BCG-resistant, and 7 (39%, CI 16% to 61%) of 18 BCG-intolerant patients. Overall, by intent-to-treat analysis, CR was thus seen in 21 (24%) of 86 subjects. Most BCG-resistant patients were failures to BCG without relapse, and had received 12 to 36 (median 12) BCG treatments; intolerant patients had received 4 to 11 treatments (median 6). Response duration ranged from 65 to 810 days, with median not yet reached (but greater than 12 months). Thirteen (15%) of 86 stopped bropirimine due to toxicity. Progression to invasive or metastatic disease during or immediately after therapy was documented in only 4 patients (6%), all nonresponders.
Bropirimine may be an alternative to cystectomy for some patients with bladder CIS who have failed or have not tolerated BCG. Further evaluation to improve responses and durability is warranted.
布罗匹明是一种口服免疫调节剂，已在膀胱和上尿路原位移行细胞癌（CIS）中显示出抗癌活性。在先前接受卡介苗（BCG）治疗的患者中也有活性记录。为了更准确地评估布罗匹明在耐BCG膀胱CIS中的疗效，进行了一项II期试验。对另外不耐受BCG毒性的患者进行了单独分析。
患者连续3天每天口服布罗匹明3.0 g，每周一次，持续长达1年。每季度进行膀胱活检和细胞学检查。完全缓解（CR）要求活检和细胞学结果为阴性。
86例入组患者中有21例不可评估。65例可评估患者中有21例（32%；第95百分位数置信区间[CI]，21%至44%）达到CR，包括47例耐BCG患者中的14例（30%，CI 17%至43%）和18例不耐受BCG患者中的7例（39%，CI 16%至61%）。总体而言，按意向性分析，86例受试者中有21例（24%）达到CR。大多数耐BCG患者对BCG治疗无效且无复发，接受了12至36次（中位数12次）BCG治疗；不耐受患者接受了4至11次治疗（中位数6次）。缓解持续时间为65至810天，中位数尚未达到（但超过12个月）。86例中有13例（15%）因毒性停止使用布罗匹明。仅4例患者（6%）在治疗期间或治疗后立即进展为浸润性或转移性疾病，均为无反应者。
对于一些BCG治疗失败或不耐受的膀胱CIS患者，布罗匹明可能是膀胱切除术的替代方案。有必要进行进一步评估以改善反应和耐久性。
