惡性腦腫瘤的化療方案課件

1、惡性腦腫瘤的化學(xué)治療1編輯版ppt惡性腦腫瘤的化學(xué)治療1編輯版pptCerebrum and Cerebellum2編輯版pptCerebrum and Cerebellum2編輯版ppt流行病學(xué)趨勢(shì)2005 (US) 18,500* 12,760Incidence 11.47 per 100,000 (annual rate)Adjusted 5 yr survival rate (1995-2000)33% adults73% children 2nd leading cause of cancer deaths in persons 腫瘤,正常腦組織暴露化療藥物高滲性BBB開放31編輯版

2、pptA/E: 頸動(dòng)脈灌注高滲溶液, 迅速改變BBB 通透性高滲性32編輯版ppt32編輯版pptBlood brain barrier disruption (BBBD) and intra-arterial methotrexate based therapy for newly diagnosed primary CNS lymphoma: The BBBD Consortium Experience.2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S 4 institutions： 1982-2005， 177 PC

3、NSL BBBD/IA MTX ；2,469 procedures PtsCRPRORRM OS(y)MPFS(y)PFS-5(y)1771014180.2%3.11.640%33編輯版pptBlood brain barrier disruptionA Phase II Trial Involving Patients with Recurrent PCNSL Treated with Carboplatin/BBBD, by Adding Rituxan (Rituximab), an anti CD-20 Antibody, to the Treatment RegimenPhase I

4、/II Study of Carboplatin, Melphalan and Etoposide Phosphate in Conjunction with Osmotic Opening of the Blood-Brain Barrier and Delayed Intravenous Sodium Thiosulfate Chemoprotection, in Subjects with Anaplastic Oligodendroglioma or OligoastrocytomaPhase II Clinical Trial of Patients with High-Grade

5、Glioma Treated with Intra-arterial Carboplatin-based Chemotherapy, Randomized to Treatment with or without Delayed Intravenous Sodium Thiosulfate as a Potential Chemoprotectant against Severe ThrombocytopeniaIntra-arterial Melphalan (L-phenylalanine mustard) Administered in Conjunction with Osmotic

6、Blood-Brain Barrier Disruption in Patients with Brain Malignancies: A Phase I StudyNeuro-Oncology Blood-Brain Barrier ProgramOregon Health & Science UniversityBlood Brain Barrier and Neuro-Oncology Program 34編輯版pptA Phase II Trial Involving Pat 替尼泊苷聯(lián)合尼莫司汀治療轉(zhuǎn)移性腦腫瘤治療方法：VM26100mg,iv,gtt,D1-3,4周重復(fù)ACNU2-

7、3mg/kg,iv,gtt,D1,4-6周重復(fù)化療前20%甘露醇250ml,iv,gtt,DXM10mg,ivACNU共計(jì)47周期，平均2.3VM26共計(jì)49周期，平均2.5中國癌癥雜志Vol9, No2, June,199935編輯版ppt 替尼泊苷聯(lián)合尼莫司汀治療轉(zhuǎn)移性腦腫瘤治療方法：ACNU共計(jì)替尼泊苷聯(lián)合尼莫司汀治療轉(zhuǎn)移性腦腫瘤研究對(duì)象男性： 11例女性： 9例年齡： 33-70歲原發(fā)腫瘤病理類型：肺癌 12例乳腺癌 1例惡性淋巴瘤 3例鼻咽癌 1例滑膜肉瘤 1例不明腫瘤 2例中國癌癥雜志Vol9, No2, June,199936編輯版ppt替尼泊苷聯(lián)合尼莫司汀治療轉(zhuǎn)移性腦腫瘤研究對(duì)

8、象中國癌癥雜志替尼泊苷聯(lián)合尼莫司汀治療轉(zhuǎn)移性腦腫瘤 臨床表現(xiàn)癥狀 例次頭痛 13惡心，嘔吐 11意識(shí)改變6肢體肌力感覺異常 10顱腦神經(jīng)受損7共濟(jì)失調(diào)1合計(jì) 48中國癌癥雜志Vol9, No2, June,199937編輯版ppt替尼泊苷聯(lián)合尼莫司汀治療轉(zhuǎn)移性腦腫瘤 臨床 替尼泊苷聯(lián)合尼莫司汀治療轉(zhuǎn)移性腦腫瘤結(jié)果：癥狀緩解率：完全緩解CR：60.4%部份緩解PR：31.6%癥狀總緩解率：91.7%顱腦CT復(fù)查：腦水腫減輕或消失 100%(16/16)完全緩解CR10%(2/20)部份緩解PR50%(10/20)總有效率(CR+PR)60%(12/20)顱腦外病灶縮小52.9%(9/17)中國癌

9、癥雜志Vol9, No2, June,199938編輯版ppt 替尼泊苷聯(lián)合尼莫司汀治療轉(zhuǎn)移性腦腫瘤結(jié)果：中國癌癥雜志V替尼泊苷聯(lián)合尼莫司汀治療轉(zhuǎn)移性腦腫瘤結(jié)果患者存活時(shí)間1-17月，平均6.5月超過6個(gè)月者11例中國癌癥雜志Vol9, No2, June,199939編輯版ppt替尼泊苷聯(lián)合尼莫司汀治療轉(zhuǎn)移性腦腫瘤結(jié)果中國癌癥雜志Vol9避開BBB的方式椎管內(nèi)化療：主要用于CNS淋巴瘤，腦膜轉(zhuǎn)移腫瘤，白血病的腦膜侵犯。40編輯版ppt避開BBB的方式椎管內(nèi)化療：40編輯版pptPhase 2 study of BCNU and temozolomide for recurrent gliob

10、lastoma multiforme: North American Brain Tumor Consortium studyNeuro-oncol. 2004 January; 6(1): 3337 可評(píng)價(jià)病人數(shù)PRSDMTTP(w)PFS-6MS(w)MPFS(w)OS-61Year532211721%341168%26%41編輯版pptPhase 2 study of BCNU and temo可評(píng)價(jià)病人數(shù)CRPRMTTP(w)PFS-6(m)42091730.3%Second-line chemotherapy with irinotecan plus carmustine in gl

11、ioblastoma recurrent or progressive after first-line temozolomide chemotherapy: a phase II study of the Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO). J Clin Oncol. 2004 Dec 1;22(23):4779-86 42編輯版ppt可評(píng)價(jià)病人數(shù)42Second-line chemothera2007年ASCO有關(guān)Gliomas的文獻(xiàn)有36篇病人數(shù)可評(píng)價(jià)病人數(shù)PRMPFS(w)MOS(w)PFS-6685959%2

12、34043%In grade III patients the median PFS was 42 weeks, the 6 month PFS was 61% the medial overall survival was 60 weeks Conclusion: The combination of bevacizumab and irinotecan is safe and demonstrates superior activity against malignant gliomas.Phase II trial of bevacizumab and irinotecan in the

13、 treatment of malignant gliomas43編輯版ppt2007年ASCO有關(guān)Gliomas的文獻(xiàn)有36篇病人數(shù)68A phase II, randomized, non-comparative clinical trial of the effect of bevacizumab (BV) alone or in combination with irinotecan (CPT) on 6-month progression free survival (PFS6) in recurrent, treatment-refractory glioblastoma (GBM

14、). J Clin Oncol 26: 2008 (May 20 suppl; abstr 2010b44編輯版pptA phase II, randomized, non-coBevacizumab plus irinotecan in recurrent glioblastoma multiforme J Clin Oncol. 2007 Oct 20;25(30):4722-9可評(píng)價(jià)病人數(shù)PRPFS-6OS-63557%46%77%45編輯版pptBevacizumab plus irinotecan inPhase II trial of irinotecan and thalidom

15、ide in adults with recurrent glioblastoma multiforme可評(píng)價(jià)病人數(shù)CRPRSDMPFS(w)MOS(w)1Year3211119133634%Neuro Oncol. 2008 Feb 26 46編輯版pptPhase II trial of irinotecan aBevacizumab and irinotecan for recurrent oligodendroglial tumors.Conclusions: This regimen is effective in recurrent oligodendrogliomas,and t

16、he overall tolerance is acceptable.ASCO 2009,Abstract 205425Pts.CRPRM-PFS(d)MOS(d)6-PFS(ms)20%52%17432842%47編輯版pptBevacizumab and irinotecan for48編輯版ppt48編輯版ppt49編輯版ppt49編輯版ppt50編輯版ppt50編輯版ppt51編輯版ppt51編輯版ppt52編輯版ppt52編輯版ppt53編輯版ppt53編輯版pptASCO 2009,Abstract 20372009年ASCO有關(guān)神經(jīng)系統(tǒng)腫瘤的文獻(xiàn)80余篇54編輯版pptASCO

17、2009,Abstract 20372009年ASA phase II study of XL184 in patients (pts) with progressive glioblastomamultiforme (GBM) in first or second relapse.Conclusions: XL184at a dose of 175 mg PO qd, has demonstrated substantial activity in ptswith progressive or recurrent GBM.ASCO 2009, Abstract 204726Pts.PRSDP

18、D6-PFS(ms)38%35%27%(9pts received bevacizumab)55編輯版pptA phase II study of XL184 in p腦膠質(zhì)瘤和轉(zhuǎn)移性瘤耐藥的研究1) 6-甲基鳥嘌呤DNA甲基轉(zhuǎn)移酶 (MGMT) (6-methylguanine-DNA hyltransferase )2) P-glycoprotein56編輯版ppt腦膠質(zhì)瘤和轉(zhuǎn)移性瘤耐藥的研究1) 6-甲基鳥嘌呤DNA甲基轉(zhuǎn)Fruehauf, J. P. et al. Clin Cancer Res 2006;12:4523-4532腦膠質(zhì)瘤和轉(zhuǎn)移性瘤耐藥的研究57編輯版pptFrueha

19、uf, J. P. et al. Clin CaFruehauf, J. P. et al. Clin Cancer Res 2006;12:4523-453258編輯版pptFruehauf, J. P. et al. Clin CaMGMT methylation status as a prognostic factor in anaplastic astrocytomas.Conclusions: MGMT methylation status is an independent prognostic factor together with age in AA.Pts.71/80(8

20、8.8%)30/71(M) 41/71(UM)MGMT methylationM-PFS(ms)48.6 38p=0.09ASCO 2009 Abstract 205259編輯版pptMGMT methylation status as a p P-gp expression in brain capillary endothelial cells suggests that P-gp may restrict drug entry into brain tumors and thus be another mechanism of drug resistance. 60編輯版ppt P-gp

21、 expression in brain capiK1735 cellsK1735 cellsMDRThe biology and mechanism of chemoresistance of brain metastases THE UNIVERSITY OF TEXAS GRAD. SCH. OF BIOMED. SCI. AT HOUSTON 199561編輯版pptK1735 K1735 MDRThe biology andBBBD(blood-brain barrier disruption)化療高滲性、緩激肽衍生物：BBB開放選擇性開放血瘤屏障(blood-tumor barri

22、er, BTB)克服化療耐藥性多藥耐藥及逆轉(zhuǎn) MGMT表達(dá)預(yù)測(cè)化療療效，避免無效化療。腦膠質(zhì)瘤和轉(zhuǎn)移性瘤耐藥的研究62編輯版ppt腦膠質(zhì)瘤和轉(zhuǎn)移性瘤耐藥的研究62編輯版ppt聯(lián)合化療提高化療敏感性VM-26和BCNU聯(lián)合顯著提高膠質(zhì)瘤對(duì)化療的敏感性機(jī)理：抑制MDR-I或P-gp過表達(dá)PCV方案顯著增強(qiáng)多形膠質(zhì)母細(xì)胞瘤對(duì)BCNU類藥制的敏感性機(jī)理：腫瘤細(xì)胞先暴露于烷化劑類藥物使瘤細(xì)胞中AGT（O6-烷基鳥嘌呤-DNA烷基化轉(zhuǎn)酶）活性受抑 AGT是增強(qiáng)腫瘤細(xì)胞對(duì)BCNU類 藥物敏感性的主要靶點(diǎn)63編輯版ppt聯(lián)合化療提高化療敏感性VM-26和BCNU聯(lián)合顯著提高膠質(zhì)瘤Randomized Comp

23、arison of Intra-arterial Versus Intravenous Infusion of ACNU for Newly Diagnosed Patients with Glioblastoma To compare the effectiveness of intra-arterial ACNUwith intravenous ACNU in newly diagnosed patients with supratentorial glioblastoma. ACNU (80mg/m2) once every 6 weeks concomitant with radiot

24、herapy. 病人數(shù)可評(píng)價(jià)病人數(shù)MS(w)PFS(w)Toxicity8482IA5924-IV5645-Journal of neuro-oncology2000,vol.49,no1,pp.63-70 64編輯版pptRandomized Comparison of Intra2008年NCCN指南成人侵潤(rùn)性低度惡性幕上星形細(xì)胞瘤/少突膠質(zhì)細(xì)胞瘤輔助化療：高劑量替莫唑胺 5/28方案復(fù)發(fā)或進(jìn)展：一線方案：替莫唑胺 5/28方案（初治）二線方案：BCUN210mg/m2 iv 6w重復(fù);,80mg/m2x3 6w重復(fù)； CCNU 110mg/m2 口服 6w重復(fù)；PCV聯(lián)合化療成人室管膜瘤：復(fù)發(fā)用vp-16,替莫唑胺 ，亞硝脲類，鉑及聯(lián)合方案原發(fā)性CNS腫瘤化療指南65編輯版ppt2008年NCCN指南成人侵潤(rùn)性低度惡性幕上星形細(xì)胞瘤/少突多形性膠母細(xì)胞瘤輔助化療：同步替莫唑胺 75