BIOMARKERS FOR MANAGEMENT OF EPITHELIAL 管理上皮细胞标志物.ppt

FRONTIERS IN TUMOR MARKERS Robert C. Bast, Jr., M.D. U.T. M.D. Anderson Cancer Center October 16, 2006 FRONTIERS IN TUMOR MARKERS:CA 125 FOR ACCELERATING DRUG EVALUATION IN OVARIAN CANCER THE CHALLENGE OF TARGETED DRUG DEVELOPMENT More than 400 New Drugs are Being Developed for Clinical Trials Many Targeted Drugs will be Effective Only in Combination Less than 4% of Cancer Patients Enter Clinical Trials Less than Half of Ovarian Cancer Patients meet RECIST Criteria Many Targeted Drugs will be Cytostatic CA 125 TO ACCELERATE PHASE II CLINICAL TRIALS Surrogate Marker for Response in Phase II Trials - A 50% and 75% Decrease in CA125 has correlated with Response Rates in 19 Phase II Trials of 14 Different Cytotoxic Drugs with 1000 Patients (Rustin, et al) - Use of CA125 could Double Accrual - Discontinue Trials with Poor Response - Expand Accrual to achieve RECIST Criteria Selection of Active Drugs in Phase II Trials for Ovarian Cancer According to CA 125 Response Rates Paclitaxel Platinum based Docetaxel Rhizoxin Etoposide Tallimustine Fosquidone Tomudex Gemcitabine Topotecan Isotretinoin/Calcitriol Oxaliplatin Altretamine CA 125 TO ACCELERATE PHASE III CLINICAL TRIALS CA 125 as an Endpoint for Time to Progression in Phase III Trials - Rise 2-fold above Normal or above Nadir - 84-94% Sensitive and 98% Specific - 80% precede or coincide with RECIST Combine with RECIST Criteria - RECIST takes Precedence - CA125 must be at the Same Time Points in Both Arms - Shorten Duration of Trials Comparison of CA-125 and Standard Definitions of Progression in the Intergroup Trial of Cisplatin and Paclitaxel Versus Cisplatin and Cyclophosphamide (Rustin et al 2006) CA 125 TO EVALUATE NOVEL CYTOSTATIC DRUGS Monitor Response to New Cytostatic Drugs - Many Targeted Therapies are Cytostatic and Stabilize Disease - Effective Drugs could arrest A Ris