2012年8月14日 訊 /生物谷BIOON/ --對(duì)晚期分化型甲狀腺癌(advanced differentiated thyroid cancer, DTC)病人的II期隨機(jī)性臨床試驗(yàn)結(jié)果表明接受口服靶向藥物凡德他尼(vandetanib)治療的病人無(wú)疾病惡化存活期要比接受安慰劑治療的那些病人長(zhǎng)將近1倍(11.2個(gè)月對(duì)5.9個(gè)月),。這項(xiàng)發(fā)現(xiàn)在線發(fā)表在Lancet Oncology期刊上,，也是第一次提供清晰的證據(jù)表明利用靶向藥物凡德他尼治療晚期分化型甲狀腺癌能夠延長(zhǎng)病人的無(wú)疾病惡化存活期(progression free survival, PFS)。就目前而言,，還不存在有效的治療方法來(lái)自醫(yī)治這種癌癥,。
在過(guò)去10年時(shí)間里，甲狀腺癌發(fā)病率在全世界增加了1倍多,。最近,，多靶點(diǎn)激酶抑制劑(multi-targeted kinase inhibitor)正成為大有希望的治療晚期分化型甲狀腺癌的候選藥物，但是在此之前,，科學(xué)家們從沒(méi)有開展過(guò)安慰劑對(duì)照臨床試驗(yàn)研究,。
在這項(xiàng)研究中，來(lái)自法國(guó)古斯塔夫-魯西研究所(Institut Gustave Roussy)的Martin Schlumberger和同事們旨在確定凡德他尼---該藥物靶向3種已知在甲狀腺癌生長(zhǎng)和擴(kuò)散中發(fā)揮作用的蛋白：內(nèi)皮生長(zhǎng)因子受體(endothelial growth factor receptor, EGFR),、血管內(nèi)皮生長(zhǎng)因子(vascular endothelial growth factor, VEGF)和感染期間發(fā)生重排的原癌基因RET(rearranged during transfection protooncogene)---是否影響無(wú)疾病惡化存活期和總存活期(overall survival, OS),。
在這項(xiàng)研究中，研究人員隨機(jī)性地將145名來(lái)自7個(gè)歐洲國(guó)家的晚期分化型甲狀腺癌病人分配為兩組：72名病人接受每天300 mg凡德他尼治療,；73名病人安慰劑治療,。
與接受安慰劑治療的那組病人相比，服用凡德他尼與病人無(wú)疾病惡化存活期顯著性提高(從5.9個(gè)月提高至11.1個(gè)月)相關(guān)聯(lián),。治療6個(gè)月后,，相比于接受安慰劑治療的那組病人,，接受凡德他尼治療的病人也擁有更加好的疾病控制率(disease control rate, DCR)。然而,，這兩組病人在總存活期上并不存在顯著性差別,。
有意思的是，在接受凡德他尼治療后,，患有更為常見(jiàn)的甲狀腺乳頭狀癌(papillary thyroid cancer, PTC)的病人擁有比甲狀腺濾泡狀癌(follicular thyroid cancer, FTC)病人和分化型甲狀腺癌病人(前兩者的中位無(wú)疾病惡化存活期為7.7個(gè)月)更加長(zhǎng)的無(wú)疾病惡化存活期(中位無(wú)疾病惡化存活期為16.2個(gè)月),。
接受凡德他尼治療的病人也經(jīng)歷著更加大的毒副作用，特別是QT間期(QTc)延長(zhǎng)時(shí)間增加,、痢疾,、無(wú)力和疲勞。接受凡德他尼治療的那組病人當(dāng)中,，還有兩名與治療相關(guān)的病人死亡,。
這些結(jié)果表明凡德他尼可能一種潛在有效的治療選擇來(lái)保持晚期分化型甲狀腺癌病人的病情穩(wěn)定，特別是甲狀腺乳頭狀癌病人而言,。不過(guò),，還需要更多的研究來(lái)更好地闡述激酶抑制劑可能對(duì)哪些晚期分化型甲狀腺癌最為有效，以便開發(fā)出個(gè)人化療法來(lái)治療晚期分化型甲狀腺癌病人,。(生物谷Bioon.com)
本文編譯自Vandetanib almost doubles progression free survival in patients with thyroid cancer
doi: 10.1016/S1470-2045(12)70335-2
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Vandetanib in locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 2 trial
Sophie Leboulleux MD a, Lars Bastholt MD b, Prof Thomas Krause MD c, Christelle de la Fouchardiere MD d, Prof Jan Tennvall MD e f, Prof Ahmad Awada MD g, José Manuel Gómez MD h, Françoise Bonichon MD i, Prof Laurence Leenhardt MD j, Christine Soufflet MD k, Muriel Licour MSc k, Prof Martin J Schlumberger
Background No effective standard treatment exists for patients with radioiodine-refractory, advanced differentiated thyroid carcinoma. We aimed to assess efficacy and safety of vandetanib, a tyrosine kinase inhibitor of RET, VEGFR and EGFR signalling, in this setting. Methods In this randomised, double-blind, phase 2 trial, we enrolled adults (aged ≥18 years) with locally advanced or metastatic differentiated thyroid carcinoma (papillary, follicular, or poorly differentiated) at 16 European medical centres. Eligible patients were sequentially randomised in a 1:1 ratio with a standard computerised scheme to receive either vandetanib 300 mg per day (vandetanib group) or matched placebo (placebo group), balanced by centre. The primary endpoint was progression-free survival (PFS) in the intention-to-treat population based on investigator assessment. This study is registered with ClinicalTrials.gov, number NCT00537095. Findings Between Sept 28, 2007, and Oct 16, 2008, we randomly allocated 72 patients to the vandetanib group and 73 patients to the placebo group. By data cutoff (Dec 2, 2009), 113 (78%) patients had progressed (52 [72%] patients in the vandetanib group and 61 [84%] in the placebo group) and 40 (28%) had died (19 [26%] patients in the vandetanib group and 21 [29%] in the placebo group). Patients who received vandetanib had longer PFS than did those who received placebo (hazard ratio [HR] 0·63, 60% CI 0·54—0·74; one-sided p=0·008): median PFS was 11·1 months (95% CI 7·7—14·0) for patients in the vandetanib group and 5·9 months (4·0—8·9) for patients in the placebo group. The most common grade 3 or worse adverse events were QTc prolongation (ten [14%] of 73 patients in the vandetanib group vs none in the placebo group), diarrhoea (seven [10%] vs none), asthenia (five [7%] vs three [4%]), and fatigue (four [5%] vs none). Two patients in the vandetanib group and one in the placebo group died from treatment-related serious adverse events (haemorrhage from skin metastases and pneumonia in the vandetanib group and pneumonia in the placebo group). Interpretation Vandetanib is the first targeted drug to show evidence of efficacy in a randomised phase 2 trial in patients with locally advanced or metastatic differentiated thyroid carcinoma. Further investigation of tyrosine-kinase inhibitors in this setting is warranted. Funding AstraZeneca.
