Abstract No.: 16026
Citation: J Clin Oncol 26: 2008 (May 20 suppl; abstr 16026)
Author(s):
J. B. Aragon-Ching, L. Jain, D. Draper, J. L. Gulley, P. M. Arlen, J. J. Wright, E. Jones, C. C. Chen, W. D. Figg, W. L. Dahut
Background: S is a multikinase inhibitor approved for renal and hepatocellular cancer. Stage I results of this open-label, two- stage trial has been previously reported. The protocol was amended to use only clinical or radiographic criteria for progression because of discordance between PSA and bone scan responses.
Methods: 4 patients (pts) were accrued for stage 2. The primary objective of this study was to determine if S was associated with a 50% probability of 4 month progression free survival (PFS). S was given continuously at a dose of 400 mg orally twice daily in 28-day cycles. CT and bone scans were obtained every 2 cycles, and PSA was measured monthly.
Results: Pt characteristics for all patients in stage 2 included a median (range) age of 66 (49 - 85), on study PSA of 68.45 ng/mL (5.8 - 995), Gleason of 8 (6 - 9), and ECOG of 1 (n=17). 22/24 (92%) had prior chemotherapy with docetaxel. All patients had bony metastases, either alone (n=11) or with soft tissue disease (n=13). All were evaluable for response after at least 2 cycles of treatment. Median duration of therapy was 2 cycles (range: < 1 to 7). One patient had a 52% PSA decline after 2 cycles with a partial response on CT. Ten pts had stable disease despite rising PSA values with a median duration on-study of 16.5 weeks. However, there were more pts who were unable to tolerate treatment (n=5) and went off-study prior to assessment of response compared to 1 pt in stage I. Dose reductions occurred in 13 of 24 pts. Grade (gr) 3 hand foot syndrome occurred in 3 pts and gr 2 in 8 pts.
Conclusions:
S monotherapy has modest activity as second-line treatment in mCRPC. Many patients treated with prior docetaxel were unable to tolerate this agent, perhaps due to hand-foot syndrome. However, there may be a subset of pts who benefit from this agent. Better refinement of target population is required to determine who may benefit or develop toxicity from this targeted agent.