Corral D A, Sella A, Pettaway C A, Amato R J, Jones D M, Ellerhorst J
Department of Urology, University of Texas M.D. Anderson Cancer Center, Houston, USA.
J Urol. 1998 Nov;160(5):1770-4.
The prognosis of patients with advanced squamous cell carcinoma of genitourinary origin is poor. While single agent chemotherapy results mainly in partial responses of short duration, data on the efficacy of combination chemotherapy are extremely limited. We determined the response rate and toxicity of a combination of 3 of the most active agents, methotrexate, cisplatin and bleomycin, in patients with advanced genitourinary squamous cell carcinoma.
Patients with metastatic or locally advanced genitourinary squamous cell carcinoma were eligible for study. Treatment consisted of 200 mg./m.2 methotrexate on days 1, 15 and 22, and 20 mg./m.2 cisplatin and 10 mg./m.2 bleomycin on days 2 through 6 during a 28-day cycle.
Of the 30 patients who enrolled in the trial 29 were evaluable for response. Objective response was achieved in 16 patients (55%, 95% confidence interval 36 to 72), 4 of whom achieved a complete response (14%). Median objective response duration was 4.7 months (range 1.9 to 39.5). Median survival of the entire group was 11.5 months (range 1.5 to 87.0). Of the patients 9 achieved disease-free status, including 6 following consolidation surgery or radiation therapy. Median survival of these 9 patients (34.4 months, range 9.6 to 87.0) was significantly greater (p = 0.0003) than that of patients who did not become disease-free (7.0 months, range 1.5 to 38.6). Grade III or IV hematological toxicity in 116 courses included neutropenia (13%) and thrombocytopenia (6%). Among 30 patients evaluable for toxicity serious nonhematological toxic effects included stomatitis (3%) and renal toxicity (7%). There was 1 death from neutropenic sepsis.
Methotrexate, cisplatin and bleomycin combination chemotherapy for genitourinary squamous cell carcinoma results in a high but short lived overall response rate, and a low complete response rate with manageable toxicity. A multidisciplinary approach to achieve disease-free status may provide the best opportunity to effect survival and should be the focus of future trials.
泌尿生殖系统来源的晚期鳞状细胞癌患者预后较差。单药化疗主要导致短期的部分缓解，关于联合化疗疗效的数据极为有限。我们确定了甲氨蝶呤、顺铂和博来霉素这三种最具活性的药物联合应用于晚期泌尿生殖系统鳞状细胞癌患者的缓解率和毒性。
转移性或局部晚期泌尿生殖系统鳞状细胞癌患者符合研究条件。治疗方案为在28天的周期中，第1、15和22天给予200mg/m²甲氨蝶呤，第2至6天给予20mg/m²顺铂和10mg/m²博来霉素。
30例入组试验的患者中有29例可评估缓解情况。16例患者获得客观缓解（55%，95%置信区间36%至72%），其中4例达到完全缓解（14%）。客观缓解的中位持续时间为4.7个月（范围1.9至39.5个月）。整个组的中位生存期为11.5个月（范围1.5至87.0个月）。9例患者达到无病状态，其中6例是在巩固手术或放疗后。这9例患者的中位生存期（34.4个月，范围9.6至87.0个月）显著长于未达到无病状态的患者（7.0个月，范围1.5至38.6个月）（p = 0.0003）。116个疗程中的III级或IV级血液学毒性包括中性粒细胞减少（13%）和血小板减少（6%）。在30例可评估毒性的患者中，严重的非血液学毒性包括口腔炎（3%）和肾毒性（7%）。有1例死于中性粒细胞减少性败血症。
甲氨蝶呤、顺铂和博来霉素联合化疗用于泌尿生殖系统鳞状细胞癌可产生较高但持续时间短的总体缓解率，完全缓解率低且毒性可控。采用多学科方法实现无病状态可能为影响生存提供最佳机会，应成为未来试验的重点。
