Abstract
506 Background: Dasatinib (Sprycel, Bristol-Myers Squibb), an oral inhibitor of SRC family kinases, inhibits proliferation in CRC cell lines and has antitumor activity in CRC xenograft models. Since treatment options for mCRC are limited after a fluoropyrimidine (F), oxaliplatin (O), and irinotecan (I), novel agents need to be explored in this setting. Methods: We conducted a phase II trial of D in unresectable, previously treated mCRC patients (pts) at 9 centers. No more than 2 prior chemotherapy regimens were permitted, which must have contained F, O and I. Disease progression on or after treatment was required. Eligible patients also had to have measurable disease per RECIST criteria; normal organ function; PS 0-2. Pts received D 70 mg PO BID continuously. CT scans were obtained every 8 weeks. The primary endpoint was progression-free survival (PFS) at 4 months. We employed a Simon, two-stage design with 19 pts enrolled in the first stage, and a second stage planned if ≥ 5 were progression-free at 4 months. 19 pts enrolled 10/07-11/08. Pt characteristics: male 58%; median age 64 (range 38-83); PS 0: 47%, 1: 53%. Results: The study was terminated after the first stage due to lack of efficacy. A median of two 4 week cycles were administered (range <1-8). 2 pts discontinued due to adverse events, 2 others withdrew, and 2 had early deaths before the first CT scan. Grade 3/4 toxicities (% pts): anemia 11%; fatigue 16%; anorexia 11%; dyspnea 11%; nausea/vomiting 11%; pleural effusion 5%; diarrhea 5%; pneumonitis 5%; dehydration 5%. There were no objective responses; 1 pt (5%) had stable disease for 7 months. PFS rate at 4 months was 5% (90% CI: 0.3, 22.6). Median PFS was 1.6 months (90% CI: 1.4, 1.8). Median overall survival was 5.1 months (90% CI: 2.4, 6.3). Conclusions: Dasatinib is inactive in previously treated mCRC pts. Novel agents are still needed for this patient population. Supported by NCI grant N01-CM-62201. [Table: see text]
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