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 evidencebut it is not currently(2012)recommended by NCCN (GIST5-7). NCCN recommends sunitinib,
A recent study evaluated the efficacy of nilotinib, a novel tyrosine kinase inhibitor (TKI) in patients pretreated with imatinib and sunitinib. Fifty-two consecutive patients treated with oral nilotinib, 400
mg twice daily, within the nilotinib compassionate use programme in 12 European cancer centres, were included in this retrospective analysis. All patients had failed both imatinib and sunitinib pretreatment. Five patients (10%; 95% confidence interval (CI) 2–18) responded to nilotinib and 19 patients (37%; 95% CI 24–50) achieved a disease stabilisation. Median progression-free survival of nilotinib treatment was 12weeks (95% CI 9–15; range 0–104) and median overall survival was 34weeks (95% CI 3–65; range 2–135). There are several supportive phase II studies.
M. Montemurro, P. Schöffski, P. Reichardt, H. Gelderblom, J. Schütte, J.T. Hartmann, R. von Moos, B. Seddon, H. Joensuu, C.M. Wendtner, E. Weber, V. Grünwald, A. Roth, S. Leyvraz Nilotinib in the treatment of advanced gastrointestinal stromal tumours resistant to both imatinib and sunitinib European Journal of Cancer - September 2009 (Vol. 45, Issue 13, Pages 2293-2297
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
M. Montemurro, P. Schöffski, P. Reichardt, H. Gelderblom, J. Schütte, J.T. Hartmann, R. von Moos, B. Seddon, H. Joensuu, C.M. Wendtner, E. Weber, V. Grünwald, A. Roth, S. Leyvraz Nilotinib in the treatment of advanced gastrointestinal stromal tumours resistant to both imatinib and sunitinib European Journal of Cancer - September 2009 (Vol. 45, Issue 13, Pages 2293-2297
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
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