顺铂、替吉奥联合尼妥株单抗治疗晚期初治贲门癌、胃癌患者的单中心、开放、平行对照的II期临床试验

1、注射用顺铂、替吉奥联合尼妥株单抗对比顺铂联合替吉奥治疗晚期初治贲门癌、胃癌患者的单中心、开放、平行对照的II期临床试验中国医学科学院肿瘤医院 内科王金万依荷芭丽. .迟DPD = dihydropyrimidine dehydrogenase; F-DPD = dihydropyrimidine dehydrogenase; F-Ala = -Ala = -fluoro-fluoro-alanine; FdUMP = active form of 5-alanine; FdUMP = active form of 5-FU;FU;GI = gastrointestinal; OPRT = or

2、otate phosphoribosyl transferase (OPRT)GI = gastrointestinal; OPRT = orotate phosphoribosyl transferase (OPRT)骨髓毒性神经毒性手足综合症心脏毒性胃肠道毒性( (腹泻, , 口腔炎) )抗肿瘤活性F-F- -丙氨酸5-FU5-FU肿瘤胃肠道骨髓FdUMPFdUMPOPRTOPRTFdUMPFdUMPFdUMPFdUMPS-1:S-1:- -DPDDPD- -吉美嘧啶GimeracilGimeracil奥替拉西钾OteracilOteracil替加氟TegafurTegafur体内代谢2L

3、iver microsomalP-450日本关于进展期胃癌一线治疗的随即对比临床研究 StudyTreatmentnRRmPFSmOS (%) (months) (months)JCOG 92051CI 5-FU10511.4 1.9 7.1 5-FU + Cisplatin10534.3 3.9 7.3JCOG 99122CI 5-FU234 9 2.9 10.8 S-123428 4.2 11.4 Irinotecan + Cisplatin23638 4.812.3SPIRITS3S-115031 4.0 11.0 S-1 + Cisplatin14954 6.0 13.0GC0301/

4、S-1160 26.9 3.610.5TOP-0024S-1 + Irinotecan155 41.5 4.512.81Ohtsu et al JCO 2003; 2Boku et al Lancet Oncol 2009, 3Koizumi et al Lancet Oncology 2008; 4Tsuburaya et al ASCO 2009Phase III S-1 global registration in AGC trial design (FLAGS) Ajani et al. J Clin Oncol 2010RCS Cisplatin 75mg/m2 iv D1 S-1

5、25mg/m2/twice day D1-21 Treatment given every 4 weeksCF Cisplatin 100mg/m2 iv D1 5-FU 1000mg/m2 /day D1-5 Treatment given every 4 weeks n=527n=526Primary objective: superiority in OS with CSOverall survival用法mg/m肿瘤ptsTox 3-4ORR. S.S.P.Ref50-75 x 2x 4W/6CRC301554%47d50-75 x 2x 4W/6Gastric28Leuco 17%Anemia 17%Thrombo 17Diarrhea 17517%58dHorikoshiASCO9650-75 x 2x 4W/6Breast28Anemia 4%stomachache 4%1140%TaguchiASCO9650-75 x 2x 4W/6ORL26Leuco 4%Anemie 4%stomachache 4%1246%FujiASCO9635x2x 4W/5Phase I15DiarrheaHFSEORTC2003 S1在不同人种代谢差异日本人 CYP2A6活性 18月感谢！ 感谢王金万教授对我的信任！ 感谢GCP赵老师对于药物的管理和发放 姜大夫、时大夫