Fudan University Shanghai cancer Center Imatinib Mechanism of action Adenosine Triphosphate Imatinib Bcr-Abl Substrate Substrate Iy rosine Phosphates Tyrosine osphate Substrate Tylosin Tyrosine Substrate Effector Effector 16 复旦大学上海医学院肿瘤学糸
Fudan University Shanghai Cancer Center 复旦大学上海医学院肿瘤学系 16 Imatinib Mechanism of Action
Fudan University Shanghai cancer Center Responses in the IRis Trial Response Initial treatment Imatinib IFN AraC (n=553) (n=553) Complete hematologic 95.3% 55.5% Major cytogenetic 85.2% 22.1% Complete cytogenetic 73.8 8.5 Partial cytogenetic 11.4% 13.6% Data referred to a median follow-up of 42 months p<0.001 for the comparison with the imatinib group RIS: International Randomised study of Interferon and sti571 17 复旦大学上海医学院肿瘤学糸
Fudan University Shanghai Cancer Center 复旦大学上海医学院肿瘤学系 17 Responses in the IRIS Trial
Fudan University Shanghai cancer Center Transplantation Vs. Targeted Therapy 2 year survival 5 year survival 10 year survival Allogeneic stem-cell transplant Total(n=135)76% 62% 53% Low risk(n=85) 78% 68% 59% Best available drug treatment Tota(n=219)89% 73% 52% Low risk(n=129) 93% 85% 62% Table 4: Survival after transplantation and drug treatment 18 复旦大学上海医学院肿瘤学糸
Fudan University Shanghai Cancer Center 复旦大学上海医学院肿瘤学系 18 Transplantation vs. Targeted Therapy
Fudan University Shanghai cancer Center Treatment Algorithm for CML CML in chronic phase Standard risk High risk Low transplantation risk Early chronic phase only Interferon alpha (or)Imatinib Imatinib Hydroxycarbamide Cytarabine Failure Failure Transplantation Failure High-dose imatinib, dasatanib, nilotinib 19 复旦大学上海医学院肿瘤学糸
Fudan University Shanghai Cancer Center 复旦大学上海医学院肿瘤学系 19 Treatment Algorithm for CML
Fudan University Shanghai cancer Center Imatinib(Glivec)Development Timeline Glivec dev My2001 FDA for CMI une 2000-November 2001 Lead compound ent with Phase Il trials Approved in ifed n a screen for initiated Europe and Japan tors of PK in syngeneic mice ( 1992-First batch June 1999- of Glivec synthesized. Phase ll trials by the Typical development timeline Discovery development Typically-8 years 20 复旦大学上海医学院肿瘤学糸
Fudan University Shanghai Cancer Center 复旦大学上海医学院肿瘤学系 20 Imatinib (Glivec) Development Timeline