Houédé Nadine, Dupuy Laura, Fléchon Aude, Beuzeboc Philippe, Gravis Gwenaëlle, Laguerre Brigitte, Théodore Christine, Culine Stéphane, Filleron Thomas, Chevreau Christine
Department of Medical Oncology, Nîmes University Hospital, Nîmes, France.
Department of Medical Oncology, Daniel Hollard Institute, Grenoble, France.
BJU Int. 2016 Mar;117(3):444-9. doi: 10.1111/bju.13054. Epub 2015 Apr 27.
To perform a phase II study evaluating a combination of gemcitabine and cisplatin in a population of patients with squamous cell carcinoma (SCC) of the penis and unresected locoregional lymph nodes and/or distant metastases, who had a poor prognosis with no standard of chemotherapy.
Eligible patients had histologically confirmed SCC of the penis with unresected locoregional lymph nodes and/or distant metastases, at initial diagnosis or at relapse, and measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Patients were treated with a combination of gemcitabine 1250 mg/m(2) on day 1 over 30 min and cisplatin 50 mg/m(2) on day 1 over 1 h, every 2 weeks. The primary endpoint was the objective response rate; secondary endpoints were time to progression (TTP) and overall survival (OS).
In all, 25 patients were included in the first phase of the study between February 2004 and January 2010 and received a median of five cycles. For the intent-to-treat population, two patients (95% confidence interval [CI] 0.98-26.0) presented an objective response and 13 patients (52%) had stable disease (95% CI 35.5-76.8). The median TTP was at 5.48 months (95% CI 2.40-11.73). After a median follow-up of 26.97 months (95% CI 17.77, not reached), nine patients were still alive. The median OS and 2-year OS rate were respectively estimated at 14.98 months (95% CI 9.76-32.9) and 39.32% (95% CI 19.15-59.03). Eleven patients had a serious adverse event (44%), 24% being relied to chemotherapy.
Every 2 weeks' administration of the combination of gemcitabine and cisplatin showed non-significant responses in patients with unresected locoregional or metastatic penile SCC. Despite manageable side-effects, this combination cannot be recommended as a standard of care, due to disappointing response rates seen in this negative study. Further regimens should be explored to improve the OS of these patients with poor prognosis.
开展一项II期研究，评估吉西他滨和顺铂联合用药方案在阴茎鳞状细胞癌（SCC）伴未切除的局部区域淋巴结和/或远处转移患者中的疗效，这类患者预后较差且尚无标准化化疗方案。
符合条件的患者在初次诊断或复发时经组织学确诊为阴茎SCC，伴有未切除的局部区域淋巴结和/或远处转移，且根据实体瘤疗效评价标准（RECIST）具有可测量病灶。患者接受吉西他滨1250 mg/m²于第1天静脉滴注30分钟和顺铂50 mg/m²于第1天静脉滴注1小时的联合治疗，每2周重复一次。主要终点为客观缓解率；次要终点为疾病进展时间（TTP）和总生存期（OS）。
2004年2月至2010年1月期间，共有25例患者纳入研究的第一阶段，接受了中位数为5个周期的治疗。在意向性治疗人群中，2例患者（95%置信区间[CI] 0.98 - 26.0）出现客观缓解，13例患者（52%）疾病稳定（95% CI 35.5 - 76.8）。中位TTP为5.48个月（95% CI 2.40 - 11.73）。中位随访26.97个月（95% CI 17.77，未达到）后，9例患者仍存活。中位OS和2年OS率分别估计为14.98个月（95% CI 9.76 - 32.9）和39.32%（95% CI 19.15 - 59.03）。11例患者发生严重不良事件（44%），其中24%与化疗相关。
对于未切除的局部区域或转移性阴茎SCC患者，每2周给予吉西他滨和顺铂联合治疗的缓解率无统计学意义。尽管副作用可控，但鉴于该阴性研究中令人失望的缓解率，该联合方案不能作为标准治疗方案推荐。应探索进一步的治疗方案以改善这些预后较差患者的总生存期。
