Trastuzumab, paclitaxel, carboplatin, and gemcitabine in advanced human epidermal growth factor receptor-2/neu-positive urothelial carcinoma:: Results of a multicenter phase II National Cancer Institute trial
Trastuzumab, paclitaxel, carboplatin, and gemcitabine in advanced human epidermal growth factor receptor-2/neu-positive urothelial carcinoma:: Results of a multicenter phase II National Cancer Institute trial
复制标题
DOI：
10.1200/jco.2006.08.0994
复制
发表时间：
2007-06-01
影响因子：
45.3
通讯作者：
Smith, David C.
中科院分区：
文献类型：
--
作者：
Hussain, Maha H. A.;MacVicar, Gary R.;Smith, David C.
目的：我们研究了吉西他滨、卡铂、曲妥珠单抗、紫杉醇治疗晚期尿路上皮癌患者的安全性和有效性（有效率、疾病进展时间、生存期），并前瞻性评估了人表皮生长因子受体2（Her-2/neu）过表达率。治疗的资格要求通过免疫组织化学（IHC）检测人表皮生长因子受体-2（Her-2/neu）过表达、基因扩增和/或血清Her-2/neu升高、既往未接受过转移化疗以及充分的器官功能（包括正常的心脏功能）。治疗包括曲妥珠单抗（T）4 mg/kg负荷剂量，随后在第1、8和15天给予2 mg/kg;紫杉醇（P）200 mg/m2，第1天;卡铂（C;曲线下面积，5），第1天;吉西他滨（G）800 mg/m2，第1和8天。结果109例登记患者中57例（52.3%）Her-2/neu阳性，48.6%为阳性。Her-2/neu阳性患者的转移部位和内脏转移多于IHC。Her-2/neu阴性患者。57例Her-2/neu阳性患者中有44例接受了TPCG治疗。中位周期数为6个（范围：1 - 12个周期）。最常见的3/4级毒性是骨髓抑制。14%的患者发生了3级感觉神经病变，22.7%的患者发生了1至3级心脏毒性（3级，n = 2：1例左心室功能障碍，1例心动过速）。有两例治疗相关死亡。44例患者中有31例（70%）缓解（5例完全缓解，26例部分缓解），44例患者中有25例（57%）确认缓解。中位进展时间和生存期分别为9.3和14.1个月，force.ConclusionWe前瞻性地描述了晚期尿路上皮癌患者的Her-2/neu状态。TPCG是可行的;心脏毒性发生率高于预期，但大多数为2级或更低。确定曲妥珠单抗的真正贡献需要随机试验。
PurposeWe investigated the safety and efficacy (response rates, time to disease progression, survival) of and paclitaxel in advanced urothelial carcinoma patients gemcitabine carboplatin trastuzumab,,, and prospectively evaluated human epidermal growth factor receptor-2 (Her-2/neu) overexpression rates.Patients and MethodsAdvanced urothelial carcinoma patients were screened for Her-2/neu overexpression. Eligibility for therapy required human epidermal growth factor receptor-2 (Her-2/neu) overexpression by immunohistochemistry (IHC), gene amplification and/or elevated serum Her-2/neu, no prior chemotherapy for metastasis, and adequate organ function including a normal cardiac function. Treatment consisted of trastuzumab (T) 4 mg/kg loading dose followed by 2 mg/kg on days 1, 8, and 15; paclitaxel (P) 200 mg/m(2) on day 1; carboplatin (C; area under the curve, 5) on day 1; and gemcitabine (G) 800 mg/m(2) on days 1 and 8. The primary end point was cardiac toxicity.ResultsFifty-seven (52.3%) of 109 registered patients were Her-2/neu positive, and 48.6% were positive Her-2/neu-positive patients had more metastatic sites and visceral metastasis than did by IHC. Her-2/neu negative patients. Forty-four of 57 Her-2/neu-positive patients were treated with TPCG. The median number of cycles was six (range, I to 12 cycles). The most common grade 3/4 toxicity was myelosuppression. Grade 3 sensory neuropathy occurred in 14% of patients, and 22.7% experienced grade I to 3 cardiac toxicity (grade 3, n = 2: one left ventricular dysfunction, one tachycardia). There were two therapy-related deaths. Thirty-one (70%) of 44 patients responded (five complete and 26 partial), and 25 (57%) of 44 were confirmed responses. Median time to progression and survival were 9.3 and 14.1 months, respectively.ConclusionWe prospectively characterized Her-2/neu status in advanced urothelial carcinoma patients. TPCG is feasible; cardiac toxicity rates were higher than projected, but the majority were grade two or lower. Determining the true contribution of trastuzumab requires a randomized trial.