卵巢癌化疗规范与进展

卵巢癌化疗规范与进展卵巢癌化疗规范与进展 State of the art in chemotherapy for ovarian cancer 复旦大学附属肿瘤医院妇瘤科 吴小华 Xiaohua Wu M.D., Ph.D. Dept. Gynecologic Oncology Fudan University Shanghai Cancer Center No Conflict of Interest 女性生殖道肿瘤女性生殖道肿瘤: : 全世界统计全世界统计1 1. Ferlay et al. GLOBOCAN 2000 IARC, WHO 2001 (www.dep.iarc.fr) Cancer New Cases Deaths Cervical 470,000 230,000 Endometrial 189,000 45,000 Ovarian 192,000 114,000 Ovarian Cancer: Scope of Problem Estimated incidence and mortality in the US (2011)1 21,550 new cases 14,600 deaths Stage III/IV: 70-75% Most recur: PFS: 10-26 mos 5-yr survival: 44% overall2 1. ACS Cancer Facts and Figures, 2011 2. Hoskins P, et al. J Clin Oncol. 1998;16:2233. Huang, Cancer 112:2289, 2008 4.86.510.511.226.72.54.44.82.54.46.39.10510152025301974199419972000Incidences ( /100,000)YearOvarian Cancer Cervical Cacner Endometrial Cancer上海市居民卵巢癌、宫颈癌、宫体癌发病率 （1974-2000，SCDC） 早期卵巢癌早期卵巢癌: : FIGO I and II 全面的分期手术 经腹全子宫/双侧卵巢输卵管切除 (TAH/BSO) 大网膜切除 淋巴结切除术（dissection）：腹主动脉旁、盆腔 腹膜和膈膜活检（ biopsies） 细胞学检查 高危 vs 低危早期卵巢癌 Staging classifications and clinical practice guidelines of gynaecologic cancers. www.figo.org 早期卵巢癌早期卵巢癌 Medical Oncology: A comprehensive review. www.cancernetwork.com textbook 低危 高危 (510% 复发率) (3040% 复发率) Stage IA or IB Stage IC Grade 1 (or 2) Grade 3 Clear cell cancer 高危早期卵巢癌高危早期卵巢癌 1. Young SGO 2003 2. Young RC. Semin Oncol 27 (3):8-10., 2000 3. ICON-1, EORTC-ACTION: J Natnl Can Inst. Vol. 95, No. 2, January 15, 2003 4. Mannel et al. GOG-175 protocol, www.cancernet.nci.nih.gov GOG1571,2 辅助化疗的随机临床试验: 3 vs 6 疗程 紫杉醇 + 卡铂 结果 6个疗程 进展危险性降低了33% 生存率无改善 Action 淋巴结阴性; 镜下腹腔种植 B 腹腔种植灶 2 cm; 淋巴结阴性 C 腹腔种植灶 >2 cm 和/或阳性腹膜后淋巴结或腹股沟 IV 远处转移 Medical Oncology: A comprehensive review. www.cancernetwork.com textbook 准确全面分期依据手术探查和 病理组织学、细胞学检查 根据腹腔内转移灶的大小对III 期再分为IIIa、IIIb、IIIc 腹膜后淋巴结转移影响分期 肝表面和肝实质转移分属III期 和IV期 Stage I: 局限于卵巢 Stage II: 局限于盆腔 Stage III: 局限于腹腔 Stage IV: 远处转移 细胞减灭术 化疗 0.0020.0040.0060.0080.00100.00120.00 months to deceased or last followup0.00.20.40.60.81.0Cum SurvivalResidual Disease no visable residual2cmSurvival Function for Residual Disease新辅助化疗新辅助化疗与与中间性细胞减灭术中间性细胞减灭术 Neoadjuvant Chemotherapy Interval Cytoreduction I. Vergote et al. N Engl J Med 2010; 363:943-953 Neoadjuvant chemotherapy is not inferior to primary cytoreductive surgery for patients with stage IIIC or IV ovarian carcinoma. No significant advantages of neoadjuvant therapy or primary debulking surgery were observed with respect to survival, adverse effects, quality of life, or postoperative morbidity or mortality. OS (ms) NAC 29 vs 30 50 一线化疗治疗一线化疗治疗: : 标准方案选择标准方案选择 铂类铂类 + + 紫杉醇类化疗紫杉醇类化疗 ( (卡铂卡铂 + + 紫杉醇紫杉醇) ) 最大程度地减灭肿瘤细胞最大程度地减灭肿瘤细胞 残余肿瘤最大径残余肿瘤最大径50% 长期生存率 20 25% 有效率有效率 病理完全有效率病理完全有效率 无进展生存率无进展生存率 生存时间生存时间 Optimal Stage III NA 50% 21 months 59 months Suboptimal III 27: 1419-1425 GOG0182-ICON5: PFS mPFS HR (95% CI) 16.1 1.000 16.4 0.990 (0.884-1.107) 16.4 0.998 (0.891-1.117) 15.3 1.094 (0.979-1.224) 15.4 1.052 (0.940-1.176) Bookman MA, et al, J Clin Oncol, 2009; 27: 1419-1425 GOG0182-ICON5: OS Bookman MA, et al, J Clin Oncol, 2009; 27: 1419-1425 mOS HR (95% CI) 40.0 1.000 40.4 0.978 (0.838-1.141) 42.8 0.972 (0.832-1.136) 39.1 1.068 (0.918-1.244) 40.2 1.035 (0.888-1.206) GOG0182-ICON5： 结论结论 加入第三种细胞毒性药物增加了血液学毒性，但是这种毒性是可控制的 在所有评价的方案中，加入第三种细胞毒药物不能改 善患者预后（包括无进展生存和总生存） Bookman MA, et al, J Clin Oncol, 2009; 27: 1419-1425 提高一线化疗疗效的可能对策提高一线化疗疗效的可能对策 1.紫杉醇/卡铂 + X+ X × 2.紫杉醇/顺铂 ：IV IP 3.紫杉醇/卡铂 ： 3周疗周疗 4.紫杉醇/卡铂 + 分子靶向治疗 Ozols, Seminars in Oncology, vol 29; Suppl 1 (Feb) 2002: 32-42. GOG 172 Cisplatin 75 mg/m2 Paclitaxel 135 mg/m2 (24 h) Cisplatin 100 mg/m2 IP d1 Paclitaxel 135 mg/m2 (24 h) IV d1 Paclitaxel 60 mg/m2 IP d8 上皮性卵巢癌 III期 满意减灭术 术前无治疗 选择性二探 Open: 23-Mar-98 Closed: 29-Jan-01 Accrual: 415 例 (可评价) I II Armstrong D, et al. N Eng J Med. 2006;354:34-43 GOG 172: PFS Copyright ©2006 Massachusetts Medical Society. All rights reserved. Armstrong D, et al. N Engl J Med. 2006;354:34-43. 0 0.2 0.4 0.6 0.8 1.0 PFS 0 12 24 36 48 60 Mos on Study CDDP (IV) Paclitaxel (IV) (n = 210) CDDP (IP) Paclitaxel (IP + IV) (n = 205) 24 vs 18 months PFS GOG 172: OS 0.0 0.2 0.4 0.6 0.8 1.0 OS 0 12 24 36 48 60 Mos on Study CDDP (IV) Paclitaxel (IV) (n = 210) CDDP (IP) Paclitaxel (IP + IV) (n = 206) 66 vs 50 months survival Copyright ©2006 Massachusetts Medical Society. All rights reserved. Armstrong D, et al. N Engl J Med. 2006;354:34-43. 级 毒性 IV, % (N = 210) IP, % (N = 201) 3/4 白细胞减少 64 76 3/4 血小板减少 4 12 3/4 胃肠道毒性 24 46 3/4 肾毒性 2 7 3/4 神经毒性 9 19 3/4 乏力 4 18 3/4 感染 6 16 3/4 代谢类 7 27 3/4 疼痛 1 11 GOG 172: 3/4度毒性度毒性 Armstrong D, et al. N Engl J Med. 2006;354:34-43. 0 20 40 60 80 100 120 140 160 治疗前 第4个周期 治疗后3-6周 治疗后12个月 IV IP P = .03 P 1 cm vs stage IV and inoperable stage III Timing of intended treatment start 4 vs >4 weeks after surgery GC