Prout G R, Shipley W U, Kaufman D S, Heney N M, Griffin P P, Althausen A F, Bassil B, Nocks B N, Parkhurst E C, Young H H
Urological Service, Massachusetts General Hospital Cancer Center, Boston.
J Urol. 1990 Nov;144(5):1128-34; discussion 1134-6. doi: 10.1016/s0022-5347(17)39674-x.
Preliminary data are presented of a clinically feasible pilot study to select a significant subgroup of patients among those with muscle-invading bladder tumors for local cure and bladder preservation, while also to offer all patients the possibility of preventing the development of distant metastases. Transurethral debulking surgical resection was combined with neoadjuvant methotrexate, cisplatin and vinblastine chemotherapy plus 2 additional courses of cisplatin and 4,000 cGy. If tumor was found on cystoscopic re-evaluation by biopsy and for cytology after cisplatin and partial irradiation (4,000 cGy.) immediate cystectomy was advised. If tumor was not found consolidation by a radiotherapy boost to a total of 6,480 cGy. plus 1 additional course of cisplatin was given. Of 53 consecutive patients the planned treatment was completed in 42 (79%). With a median followup of 26 months (range 15 to 42 months), 72% of all entered patients were alive, 70% have not required cystectomy and 74% have not had distant metastases. Among the 42 patients who completed the planned protocol chemotherapy dose reductions were required in 39% for stomatitis, bone marrow depression and/or renal dysfunction. There were 2 serious complications but no treatment-related sepsis, deaths or significant renal dysfunction. Eight patients underwent immediate radical cystectomy because of positive biopsy and/or cytology results after 4,000 cGy., while 34 completed full chemotherapy and radiotherapy without any significant bladder or bowel injury. Of 42 patients 22 (52%) have maintained the bladder without any recurrence, and of those selected for full chemotherapy and radiotherapy this number increased to 65%. To date 12 patients have persistent or recurrent bladder tumors: 5 (15%) had invasive tumors treated by cystectomy and 7 (21%) had carcinoma in situ treated by intravesical therapy. The true success of this or other selective bladder-preserving treatments will require 3 to 5 years of followup to be confident that such treatment has sterilized the bladder of cancer. This feasibility study has been clinically practical, modestly well tolerated and encouraging for the significant proportion of patients with a sustained complete response and for the 70% over-all survival rate at 2 years. To evaluate critically the efficacy of methotrexate, cisplatin and vinblastine chemotherapy in the prevention of occult distant micrometastases and in increasing the rate of successful bladder preservation, in May 1988 we began a randomized phase 3 trial with and without neoadjuvant methotrexate, cisplatin and vinblastine chemotherapy.
本文呈现了一项临床可行的初步试验研究数据，该研究旨在从肌层浸润性膀胱肿瘤患者中挑选出一个有意义的亚组，以实现局部治愈和膀胱保留，同时为所有患者提供预防远处转移发生的可能性。经尿道减瘤手术切除联合新辅助甲氨蝶呤、顺铂和长春碱化疗，再加上2个疗程的顺铂和4000 cGy的放疗。如果在顺铂和部分照射（4000 cGy）后通过活检和细胞学进行膀胱镜复查时发现肿瘤，则建议立即进行膀胱切除术。如果未发现肿瘤，则通过放疗加量至总量6480 cGy并再给予1个疗程的顺铂进行巩固治疗。在连续的53例患者中，42例（79%）完成了计划治疗。中位随访时间为26个月（范围15至42个月），所有入组患者中有72%存活，70%无需进行膀胱切除术，74%未发生远处转移。在完成计划方案的42例患者中，39%因口腔炎、骨髓抑制和/或肾功能不全需要减少化疗剂量。有2例严重并发症，但没有与治疗相关的败血症、死亡或严重肾功能不全。8例患者因在4000 cGy照射后活检和/或细胞学结果呈阳性而立即接受了根治性膀胱切除术，而34例患者完成了完整的化疗和放疗，没有出现任何明显的膀胱或肠道损伤。在42例患者中，22例（52%）保留了膀胱且无任何复发，在选择进行完整化疗和放疗的患者中，这一比例增至65%。迄今为止，有12例患者存在持续性或复发性膀胱肿瘤：5例（15%）有浸润性肿瘤，通过膀胱切除术治疗，7例（21%）有原位癌，通过膀胱内治疗。这种或其他选择性膀胱保留治疗的真正成功需要3至5年的随访，才能确定这种治疗已使膀胱无癌。这项可行性研究在临床上是可行的，耐受性尚可，对于相当一部分有持续完全缓解的患者以及2年总体生存率达70%的情况令人鼓舞。为了严格评估甲氨蝶呤、顺铂和长春碱化疗在预防隐匿性远处微转移以及提高成功保留膀胱率方面的疗效，1988年5月我们开始了一项有或无新辅助甲氨蝶呤、顺铂和长春碱化疗的随机3期试验。
