摘要:胃癌嚴(yán)重危害人類健康,大多數(shù)胃癌患者在確診時分期較晚,因而積極有效的內(nèi)科治療越來越受到重視。本文就姑息性化療、靶向治療的研究進(jìn)展進(jìn)行簡要闡述。
關(guān)鍵詞:晚期胃癌;姑息化療;靶向治療
全球范圍內(nèi),胃癌是最常見的癌癥之一,位居癌癥死因第二位[1]。胃癌發(fā)病率最高是在東亞、東歐、南美地區(qū)[2,3],胃癌早期癥狀不典型,一經(jīng)診斷,往往已經(jīng)處于晚期失去手術(shù)機會。 所以內(nèi)科治療尤為重要。
1姑息化療
JCOG9912研究[4]隨機分成5-FU組、IP組和S-1組。結(jié)果顯示,三組的RR分別為9%、38%和28%,中位PFS分別為2.9個月、4.8個月和4.2個月,中位OS分別為10.8個月、12.3個月和11.4個月。
FLAGS[5]CS方案和CF方案一線治療晚期胃癌的生存無顯著差異,但CS方案更為安全。對于彌漫型患者,CS方案可能優(yōu)于CF方案(9.0個月vs 7.1個月),仍有待更多的前瞻性研究。
SPIRITS[6]S-1+順鉑組和S-1單藥組的中位OS分別為13.0個月和11.0個月;中位PFS分別為6.0個月和4.0個月; RR分別為54%和31%。S-1+順鉑組出現(xiàn)3~4度不良反應(yīng)較多,但兩組均未出現(xiàn)治療相關(guān)性死亡。
ML17032[7]中, XP 組與CF 組的中位PFS 分別為5. 6 個月vs. 5. 0 個月,OS 分別為10.5個月vs9.3個月,客觀有效率分別為41% vs29%。毒副反應(yīng)均與CF 組相似。
目前,國內(nèi)外最新的Ⅲ期臨床試驗結(jié)果顯示,接受聯(lián)合化療的中位OS在8.6個月到13.0個月之間[8-11]。
2靶向治療
2.1抗HER2單抗 Bang等[12]報道了ToGA研究結(jié)果。與單純化療組相比,曲妥珠單抗聯(lián)合標(biāo)準(zhǔn)化療方案總生存期延長了2.7mo。GI[13,14]會議上 ,分別報告了曲妥珠單抗聯(lián)合化療在療效指標(biāo)方面,曲妥珠單抗聯(lián)合標(biāo)準(zhǔn)化療方案較單一化療方案其總生存延長了2.7個月。
2.2抗EGFR 單抗 西妥昔單抗聯(lián)合卡培他濱與順鉑一線治療晚期胃癌的隨機對照Ⅲ期臨床研究(EXPAND)[15]。該研究未達(dá)到主要研究終點,即聯(lián)合治療組并未延長PFS。(REAL3)結(jié)果[16]該研究以O(shè)S 為主要研究終點,聯(lián)合帕尼單抗組vs. 單獨化療組:PFS 6.0 個月vs. 7.4 個月;OS 8.8 個月vs. 11.3 個月。
2.3抗VEGF 單抗 AVAGAST[17]中位OS 聯(lián)合治療組為12.1 個月,對照組為10.1個月,沒有達(dá)到主要研究終點。
3結(jié)語
胃癌是異質(zhì)性較強的疾病,其治療仍面臨諸多挑戰(zhàn)。需進(jìn)一步探索新的化療藥物、優(yōu)化藥物組合、開展多學(xué)科綜合治療。
參考文獻(xiàn):
[1]Van Cutsem E. The treatment of advanced gastric cancer: new finding on the activity of the taxanes[J].On-cologist,2004,9(Suppl 2):9-15.
[2]Ahmedin Jemal DVM, Freddie Bray,Melissa M,et al. Global cancer statistics?[J].A Cancer Journal for Clinicians,2011,61(2): 69-90.
[3]鄒小農(nóng),孫喜斌,陳萬青,等.2003-2007年中國胃癌發(fā)病與死亡情況分析[J].腫瘤,2012,32(2):109-114.
[4]Randomized phase Ⅲ study of 5-fluorouracil (5-FU) alone versus combination of irinotecan and cisplatin (CP) versus S-1 alone in advanced gastric cancer (JCOG9912)[J]. J Clin Oncol,2007, 25(18S): LBA4513.
[5]A. Ajani, W. Rodriquez, G. Bodoky, et al. Multicenter phase III comparison of cisplatin/S-1 (CS) with cisplatin/5-FU (CF)[J].J Clin Oncol,2009,27(15s):4511.
[6]Koizumi W, Narahara H, Hara T, et al. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial[J].Lancet Oncol,2008,9(3):215-221.
[7]Kang YK,Kang WK,Shin DB,et al. Capecitabine /cisplatin versus 5-fluorouracil /cisplatin a randomised phase Ⅲ noninferiority trial [J]. Ann Oncol,2009,20( 4) : 666 - 673.
[8]Van Cutsem E, Moiseyenko VM, Tjulandin S, et al. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group[J]. J Clin Oncol,2006,24(31): 4991-4997.
[9]Forman D, Burley VJ. Gastric cancer: global pattern of the disease and an overview of environmental risk factors[J]. Best practice research,2006, 20(4): 633-649.
[10]Wagner AD, Grothe W, Haerting J, et al. Chemotherapy in advanced gastric cancer: a systematic review and meta-analysis based on aggregate data[J]. J Clin Oncol,2006,24(18): 2903-2909.
[11]Cunningham D, Starling N, Rao S, et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer[J]. N Engl J Med,2008, 358(1): 36-46.
[12]Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L,Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase3,open-label, randomised controlled trial[J]. Lancet ,2010,376: 687-697.
[13]Van Cutsem E, Kang Y, Chung HC,et al. Efficacy Results from the ToGA trial: A phase Ⅲ study of trastuzumab added to standard chemotherapy (CT) in first-line human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (GC) [J]. J Clin Oncol,2009, 27(18Suppl): LBA4509.
[14]Chung HC, Bang Y, Van Cutsem E,et al. (Q)-TWiST analysis of trastuzumab plus fluoropyrimidine/cisp-latin (T-XP/FP) vers us XP/FP alone as first-line therapy for advanced HER2-positive gastric cancer[J]. J ClinOncol, 2010, 28(15 Suppl): abstr 4048.
[15]Lordick F, Kang YK, Chung HC, et al. Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial[J].Lancet Oncol,2013, 14: 490-499.
[16]Waddell T, Chau I, Cunningham D, et al. Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3): a randomised, open-label phase 3 trial[J]. Lancet Oncol, 2013, 14: 481-489.
[17]Ohtsu A, Shah MA, Van Cutsem E, et al. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study[J].J ClinOncol, 2011, 29: 3968-3976.
編輯/孫杰