SARC003: Phase II Study of Gemcitabine & Docetaxel in Recurrent Ewings Sarcoma, Osteosarcoma, or Unresectable/Locally Recurrent Chondrosarcoma Elizabeth Fox, NCI Pediatric Oncology Branch Shreyaskumar Patel, MD Anderson Cancer Center

675 mg/m2 IV over 90 min (7.5 mg/m2/min) Dose and Schedule DAY 1 DAY 8 DAY 9 Gemcitabine 675 mg/m2 IV over 90 min (7.5 mg/m2/min) Docetaxel 75 mg/m2 IV over 60 min Gemcitabine 675 mg/m2 IV over 90 min Filgrastim or Pegfilgrastim Cycle Duration 21 days Restaging prior to cycles 1, 3, 5, 7, 9, 13, 15, then every 4th cycle and off study Target Response rate: OS: 35% EWS: 35% Chondrosarcoma: 20%

Patient Characteristics Enrolled/Evaluable: 42/42 Median Age (range): 36.3y (12.9-77.6y) Number ≤ 21 yrs 5 Male:Female 24:18 Osteosarcoma 14 Ewings Sarcoma Chondrosarcoma

Toxicity (Cycle 1)

Toxicity (Cycle 2+, n=86 cycles) Seven patients (17%) have discontinued therapy due to toxicity Five patients (12%) withdrew consent

Response (RECIST) Cohort Off Study # Cycles Median (range) On Study Best Response OS (n=14) 14 2 (1-14+) Closed 1 PR EWS 2 (1-12) none 2 PR Chondro 13 2 (1-10+) 1 (C10+) None confirmed

Response in EWS Baseline Prior to C9 Prior to C12

Interim Conclusions Toxicity, particularly hematological toxicity, requires close monitoring. Pharmacokinetic samples collected on 23 patients (49%), batched for analysis. Trial Status Osteosarcoma cohort closed due to inactivity. Accrual to EWS and Chondrosarcoma cohorts ongoing. 2 PR’s in EWS cohort Protocol Amendment F distributed 5/18/2007 Remove maximum number of cycles Update toxicities in consent