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1、SUN YAT-SEN UNIVERSITY CANCER CENTER 晚期头颈癌化疗和靶向治疗进展晚期头颈癌化疗和靶向治疗进展中山大学肿瘤医院内科中山大学肿瘤医院内科 黄慧强黄慧强Tel: 020-87343355huang_ sysu SUN YAT-SEN UNIVERSITY CANCER CENTER 中中 山山 大大 学学 肿肿 瘤瘤 医医 院院内内容容 头颈癌常规化疗头颈癌常规化疗 头颈癌靶向治疗头颈癌靶向治疗SUN YAT-SEN UNIVERSITY CANCER CENTER 中中 山山 大大 学学 肿肿 瘤瘤 医医 院院Kish.T.A , AL - Sarraf. M
2、 报告：报告：80年代初，美国年代初，美国Wayne州立大学州立大学 26例晚期初治头颈鳞癌例晚期初治头颈鳞癌DDP 100mg/m2ivd第第 1天天5-FU 1000mg/m2/d，civ 120 h， 第第2-6天天 缓解率缓解率88.5%，CR率率19.2%；证证 明：明： DDP与与5-Fu 有协同作用有协同作用SUN YAT-SEN UNIVERSITY CANCER CENTER 中中 山山 大大 学学 肿肿 瘤瘤 医医 院院Randomized controlled studies: SUMMARY, PF + Paclitaxel PF PF + Docetaxel PFPa
3、clitaxel + DDP = PF未化疗的患者未化疗的患者SUN YAT-SEN UNIVERSITY CANCER CENTER 中中 山山 大大 学学 肿肿 瘤瘤 医医 院院如何进一步提高化疗疗效如何进一步提高化疗疗效DDP + 5-FU civ +/- Docetaxel DDP + Xeloda + DocetaxelDDP + S-1 + Docetaxel, 70%,15%SUN YAT-SEN UNIVERSITY CANCER CENTER DXDDXD治疗难治性转移鼻咽治疗难治性转移鼻咽 癌的初步报告癌的初步报告 DDP + Xeloda + Docetaxel, DXD
4、中山大学肿瘤医院中山大学肿瘤医院 黄慧强等黄慧强等SUN YAT-SEN UNIVERSITY CANCER CENTER 中中 山山 大大 学学 肿肿 瘤瘤 医医 院院客客 观观 疗疗 效效N CR (%) CR+PR (%) 中位缓解期（月）中位缓解期（月） 23 29 87 8（2 - 80） 2* 100* 仅有骨转移仅有骨转移YGH,难治难治NPC,DXD 化疗后化疗后CCR 80 月月SUN YAT-SEN UNIVERSITY CANCER CENTER 中中 山山 大大 学学 肿肿 瘤瘤 医医 院院Results， DXD 有效率有效率86，CR:48%; SD:4%; PD:
5、8% toxicities :neutropenia (11 %), anemia (10.5%), nausea and vomiting (28%), diarrhea (8%), mucositis (3%), reversible alopecia (100%), fatigue (10%), grade 3 renal toxicity (5%), hand-foot syndrome (2.5%)Beldjilali et al 2009 ASCO(suppl; abstr 6045) SUN YAT-SEN UNIVERSITY CANCER CENTER 中中 山山 大大 学学
6、 肿肿 瘤瘤 医医 院院PF or DCF follow by CRT vs. CRT as 1st-line treatment of LAHNC2009 ASCO abstract 6007; randomized phase III trial unresectable, measurable LAHNC，n=439 T475%, N2-361%; 156 pts received PF, 155 pts received DCF; 128 pts received CRT directly;IC/CRTCRTp valuem- TTF 12.5 mos 4.9 mos 2-line t
7、herapies SUN YAT-SEN UNIVERSITY CANCER CENTER 中中 山山 大大 学学 肿肿 瘤瘤 医医 院院ERBITUX + carboplatin is active in NPC failing DDP therapyChan et al. J Clin Oncol 2005;23:3568-3576Efficacy% (n=60)Partial response12Stable disease48Objective response rate12Disease control 60Overall survival 7.7 monthsSUN YAT-SEN
8、 UNIVERSITY CANCER CENTER 中中 山山 大大 学学 肿肿 瘤瘤 医医 院院Cetuximab in Combination With DDP/CBP+5-Fu 53 pts ,ORR 36% grade 3/4 AE were leucopenia (38%), asthenia (25%), vomiting (14%), and thrombocytopenia (15%) Cetuximab, DDP/CBP,+ FU was well tolerated and active in recurrent/metastatic SCCHN J Clin Oncol,
9、 ; Vol , No (5/24/2006): pp. SUN YAT-SEN UNIVERSITY CANCER CENTER 中中 山山 大大 学学 肿肿 瘤瘤 医医 院院EXTREME: Randomized phase III study in first- line recurrent/metastatic SCCHNRANDOMIZEDGroup A Erbitux 400 mg/m2, 250 mg/m2weekly + carboplatin (AUC 5, d1) OR cisplatin (100 mg/m2IV, d1) + 5-FU (1000 mg/m2/d IV,
10、 d1-4) 21-day cycles (6 cycles maximum)Group Bcarboplatin (AUC 5, d1) OR cisplatin (100 mg/m2IV, d1) + 5-FU (1000 mg/m2/day IV, d14) 21-day cycles (6 cycles maximum)No treatmentErbituxProgressive disease or unacceptable toxicityPatients stratified according to: KPS (80 vs 80) Prior chemotherapy (yes
11、 vs no)Vermorken et al. ECCO 2007SUN YAT-SEN UNIVERSITY CANCER CENTER 中中 山山 大大 学学 肿肿 瘤瘤 医医 院院EXTREME: Most relevant grade 3/4 adverse eventsPlatinum/5-FU (n=215)Erbitux + platinum/5-FU (n=214)DSMB: February 10, 20060510152025AnemiaNeutropeniaThrombocytopeniaNauseaVomitingDiarrheaStomatitisDyspneaPne
12、umoniaAcne-like rashInfusion reactionPatients (%)Vermorken et al. ECCO 2007SUN YAT-SEN UNIVERSITY CANCER CENTER 中中 山山 大大 学学 肿肿 瘤瘤 医医 院院SUN YAT-SEN UNIVERSITY CANCER CENTER 中中 山山 大大 学学 肿肿 瘤瘤 医医 院院EXTREME: overall response rateaStratified Cochran-Mantel-Haenszel Test.bObjective response rate = CR + PR
13、.cDisease control rate = CR + PR + SD.Platinum / FU + Erbitux (n=222)Platinum/ 5- FU (n=220)p-valueaObjective response rateb,35.619.50.0001Disease control ratec,81.1600.0001Vermorken et al. ECCO 2007SUN YAT-SEN UNIVERSITY CANCER CENTER 中中 山山 大大 学学 肿肿 瘤瘤 医医 院院SUN YAT-SEN UNIVERSITY CANCER CENTER 中中 山
14、山 大大 学学 肿肿 瘤瘤 医医 院院Biomarker potential of gene copy number by FISH in the phase III EXTREME study: Plantinum-based CT+cetuximab in 1st-line R/M SCCHNNo significant correlation between FISH status and efficacy outcomes with either CT or CT+ Erbitux Patients with R/M SCCHN benefit from treatment with
15、Erbitux regardless of EGFR copy number, as determined by FISHLicitra et al., Abstract 6005, ASCO 2009SUN YAT-SEN UNIVERSITY CANCER CENTER C225 + 放放 疗疗SUN YAT-SEN UNIVERSITY CANCER CENTER 中中 山山 大大 学学 肿肿 瘤瘤 医医 院院ERBITUX + RT prolongs survival compared with CRT in locally advanced SCCHNBonner et al.N E
16、ngl J Med 2006;354:567-578; Denis et al. J Clin Oncol 2004;22:69-76; Huguenin P et al. J Clin Oncol 2004;22:4665-4673; Semrau et al. Int J Radiat Oncol Biol Phys 2006; In PressSUN YAT-SEN UNIVERSITY CANCER CENTER 中中 山山 大大 学学 肿肿 瘤瘤 医医 院院ERBITUX + RT prolongs survival over RT alone in locally advanced SCCHN (2)Bonner et al. N En
