Sprycel (dasatinib) is currently in trials for various types of sarcoma. Dasatinib, a small-molecule inhibitor of Src kinase activity, is a promising cancer therapeutic agent with oral bioavailability. Currently, dasatinib is approved for use in imatinib-refractory chronic myelogenous leukemia. The FDA also granted full approval of Sprycel for the treatment of adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) with resistance or intolerance to prior therapy.
Despite the high rate of clinical benefit of imatinib in GIST patients, more than half of GIST patients eventually develop primary or secondary resistance to imatinib, resulting in the progression of the disease. It has also been reported that about 5% of patients are intolerant to imatinib.
Sprycel and Tassigna(nilotinib) are natural alternatives to Geleevec. In CML, Sprycel is effective in patients who faield Gleevec. The FDA sited four single-arm studies involving over 400 patients who were no longer responsive to Gleevec. The response rate to Sprycel was 45% for patients in chronic phase (CP) of CML with responses lasting 6 months or more. More advanced stages of CML and ALL had less frequent and less long lasting responses.
For GIST, however, there is no credible evidence that Sprycel is effective, especially after imatinib. Nilotinib does have such evidence and is now recommended by NCCN (p. 35). NCCN recommends sunitinib, sorafenib or nilotinib. After progression on Gleevec is recommends sunitinib only (p.51, MS-14).
Clinicaltrials.gov lists a study of front line dasatinib and one, now terminated, for those with GIST who progress after imatinib and sunitinib.
As such, Sprycel is experimental in Gleevec resistant GIST.
Masayoshi Yamamoto et al, Current clinical strategy for imatinib-resistant gastrointestinal stromal tumors Journal Clinical Journal of Gastroenterology Issue Volume 2, Number 3 / June, 2009 , 1865-7257
Baccarani M, Kantarjian HM, Apperly JF, et al. Efficacy of dasatinib (Sprycel®) in patients (pts) with chronic phase chronic myelogenous leukemia (CP-CML) resistant to or intolerant of imatinib: Updated results of CA180013 ‘START-C study. Blood 2006;108:53a, abstract 164.
nccn.org, soft tissue sarcoma
Sprycel (dasatinib) is currently in trials for various types of sarcoma. Dasatinib, a small-molecule inhibitor of Src kinase activity, is a promising cancer therapeutic agent with oral bioavailability. Currently, dasatinib is approved for use in imatinib-refractory chronic myelogenous leukemia. The FDA also granted full approval of Sprycel for the treatment of adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) with resistance or intolerance to prior therapy.
Despite the high rate of clinical benefit of imatinib in GIST patients, more than half of GIST patients eventually develop primary or secondary resistance to imatinib, resulting in the progression of the disease. It has also been reported that about 5% of patients are intolerant to imatinib.
Sprycel and Tassigna(nilotinib) are natural alternatives to Geleevec. In CML, Sprycel is effective in patients who faield Gleevec. The FDA sited four single-arm studies involving over 400 patients who were no longer responsive to Gleevec. The response rate to Sprycel was 45% for patients in chronic phase (CP) of CML with responses lasting 6 months or more. More advanced stages of CML and ALL had less frequent and less long lasting responses.
For GIST, however, there is no credible evidence that Sprycel is effective, especially after imatinib. Nilotinib does have such evidence and is now recommended by NCCN (p. 35). NCCN recommends sunitinib, sorafenib or nilotinib. After progression on Gleevec is recommends sunitinib only (p.51, MS-14).
Clinicaltrials.gov lists a study of front line dasatinib and one, now terminated, for those with GIST who progress after imatinib and sunitinib.
As such, Sprycel is experimental in Gleevec resistant GIST.
Masayoshi Yamamoto et al, Current clinical strategy for imatinib-resistant gastrointestinal stromal tumors Journal Clinical Journal of Gastroenterology Issue Volume 2, Number 3 / June, 2009 , 1865-7257
Baccarani M, Kantarjian HM, Apperly JF, et al. Efficacy of dasatinib (Sprycel®) in patients (pts) with chronic phase chronic myelogenous leukemia (CP-CML) resistant to or intolerant of imatinib: Updated results of CA180013 ‘START-C study. Blood 2006;108:53a, abstract 164.
nccn.org, soft tissue sarcoma