12月12日,，一項在線發(fā)表在J Clin Oncol雜志上的一項II / III期研究"Randomized Phase II/III Trial Assessing Gemcitabine/Carboplatin and Methotrexate/Carboplatin/Vinblastine in Patients With Advanced Urothelial Cancer Who Are Unfit for Cisplatin-Based Chemotherapy: EORTC Study 30986"顯示，當(dāng)一些晚期尿路上皮癌患者不能接受順鉑治療時，卡鉑為基礎(chǔ)的方案同樣有效,。
研究者發(fā)現(xiàn),，在兩種卡鉑類方案中,，吉西他濱/卡鉑（GC）比甲氨蝶呤/卡鉑/長春堿 (M-CAVI)更加耐受,。領(lǐng)導(dǎo)這次試驗的Maria De Santis博士講到，這是首次明確界定不能通過順鉑化療獲益的人群,。順鉑是標(biāo)準(zhǔn)療法,，但是因為腎功能不全和身體狀態(tài)不佳導(dǎo)致一半以上的病人不能使用。
為了評估替代順鉑的方案，研究人員隨機(jī)分配了238名未化療病人使用GC或M-CAVI治療,，這些患者來自29所醫(yī)院,。所有患者都不符合順鉑為基礎(chǔ)化療的資格。
中位隨訪期超過4.5年,，41.2%的GC組病人有完全或部分緩解（包括6個未經(jīng)證實的反應(yīng)）,，M-CAVI組為30.3%（包括11個未經(jīng)證實的反應(yīng)）。
總體和無進(jìn)展生存期無組間差異,，但是只考慮明確的反應(yīng)時,，是有統(tǒng)計學(xué)差異的。
意向性治療分析顯示,，GC組的中位總體生存期為9.3個月,，M-CAVI為8.1個月。無進(jìn)展生存期分別為5.8和4.2個月,。
盡管在整體結(jié)局上有相似性，但在M-CAVI組有更為嚴(yán)重的不良事件,，該組的死亡率,、血小板減少伴出血、腎毒性和其他突發(fā)事件發(fā)生率顯著升高（21.2% vs 9.3%）,。
De Santis博士說,，吉西他濱/卡鉑毒性小于M-CAVI，將來或許成為不能用順鉑治療患者的首選治療方案或是將來臨床試驗的參考方案,。（生物谷Bioon.com）
doi:10.1200/JCO.2011.37.3571
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Randomized Phase II/III Trial Assessing Gemcitabine/Carboplatin and Methotrexate/Carboplatin/Vinblastine in Patients With Advanced Urothelial Cancer Who Are Unfit for Cisplatin-Based Chemotherapy: EORTC Study 30986.
De Santis M, Bellmunt J, Mead G, Kerst JM, Leahy M, Maroto P, Gil T, Marreaud S, Daugaard G, Skoneczna I, Collette S, Lorent J, de Wit R, Sylvester R
PURPOSEThis is the first randomized phase II/III trial comparing two carboplatin-based chemotherapy regimens in patients with urothelial cancer who are ineligible ("unfit") for cisplatin chemotherapy. PATIENTS AND METHODSThe primary objective of the phase III part of this study was to compare the overall survival (OS) of chemotherapy-naive patients with measurable disease and an impaired renal function (glomerular filtration rate < 60 but > 30 mL/min) and/or performance score of 2 who were randomly assigned to receive either gemcitabine/carboplatin (GC) or methotrexate/carboplatin/vinblastine (M-CAVI). To detect an increase of 50% in median survival with GC compared with M-CAVI (13.5 v 9 months) based on a two-sided log-rank test at error rates α = .05 and β = .20, 225 patients were required. Secondary end points were overall response rate (ORR), progression-free survival (PFS), toxicity, and quality of life.ResultsIn all, 238 patients were randomly assigned by 29 institutions over a period of 7 years. The median follow-up was 4.5 years. Best ORRs were 41.2% (36.1% confirmed response) for patients receiving GC versus 30.3% (21.0% confirmed response) for patients receiving M-CAVI (P = .08). Median OS was 9.3 months in the GC arm and 8.1 months in the M-CAVI arm (P = .64). There was no difference in PFS (P = .78) between the two arms. Severe acute toxicity (death, grade 4 thrombocytopenia with bleeding, grade 3 or 4 renal toxicity, neutropenic fever, or mucositis) was observed in 9.3% of patients receiving GC and 21.2% of patients receiving M-CAVI. CONCLUSIONThere were no significant differences in efficacy between the two treatment groups. The incidence of severe acute toxicities was higher for those receiving M-CAVI.
