SKI606 is Bosutinib. Findings were presented at the most recent ASCO conference.
Regards, Pat Elliott Phoenix, Arizona http://www.ascopost.com/articles/september-2010/bosutinib-may-have-a-major-r ole-in-cml-.aspx Bosutinib May Have a Major Role in CML By Alice Goodman September 2010, Volume 1, Issue 4 On the heels of the positive studies of nilotinib (Tasigna) and dasatinib (Sprycel) as first-line therapy for chronic-phase chronic myeloid leukemia (CML), promising results for another tyrosine kinase inhibitor-bosutinib-were presented at the 2010 ASCO Annual Meeting. Two separate studies reported at the meeting showed that bosutinib was effective as second- and third-line therapy in patients for whom imatinib and other therapies have failed. The first study found that half of the patients who were either imatinib-resistant or imatinib-intolerant achieved a complete cytogenetic response (CCyR) with bosutinib.1 The second study suggested that bosutinib was also effective as third-line therapy in chronic-phase CML, after failure on first-line imatinib and second-line dasatinib.2 We see very good activity for bosutinib in both second- and third-line therapy, with high levels of response," said lead author of the first study and senior author of the second study, Jorge E. Cortes, MD, Chair of the CML Section, Department of Leukemia at M.D. Anderson Cancer Center in Houston. Noting that toxicity of bosutinib was acceptable in these studies, he commented, "Bosutinib is a contender for a major role in the treatment of CML." Bosutinib is 30 times more potent than imatinib. This drug inhibits BCR-ABL signaling in CML cells and is active against all imatinib-resistant mutations, with the exception of the T315-I clone. Pfizer is sponsoring a phase III study of bosutinib as first-line therapy for patients with newly diagnosed chronic-phase CML. The trial is currently accruing patients. Second-line Therapy Dr. Cortes presented a multicenter phase I/II study in patients for whom prior imatinib therapy failed.1 Phase I was a dose-finding study that included 18 patients treated with bosutinib at 400, 500, or 600 mg/d. The phase II trial included 276 patients treated with bosutinib at 500 mg/d. The median age was 52 years, median time from diagnosis was 4 years, and patients had been on prior imatinib therapy for a median of 2.3 years. About 70% were imatinib-resistant, and 30% were imatinib-intolerant. At a median follow-up of almost 3 years, median duration of bosutinib therapy was 13.7 months. Three-quarters of patients had dose interruptions, and 45% required dose reductions. The dose of bosutinib was escalated to 600 mg in 33 patients (22%). Of the 109 patients evaluable for best response, an overall response was seen in 102 (94%), and complete hematologic response was observed in 99 (91%). Of the 214 patients analyzed for cytogenetic response (CyR), a major CyR was observed in 136 (64%) and complete CyR was seen in 106 (50%). Of the 151 patients evaluated for molecular response, a major molecular response was seen in 79 patients (51%) and a complete molecular response was seen in 49 (32%). Response rates were higher in imatinib-intolerant patients than in imatinib-resistant patients. Time to achieve a major CyR was about 6 months, but responses continue to improve over time, Dr. Cortes said, and are continuing well into the second and third years of therapy. At 2 years, median progression-free survival (PFS) was 77% in imatinib-resistant patients and 86% in imatinib-intolerant patients. "The majority of patients are still alive," Dr. Cortes said. Adverse events on treatment included diarrhea in 84% (grade 3/4, 9%), rash in 34% (grade 3/4, 9%), nausea in 44% (grade 3/4, 2%), and vomiting in 36% (grade 3/4, 3%). Fluid retention was uncommon, and pleural effusion occurred in 3%. The rates of grade 3 or 4 myelosuppression were as follows: thrombocytopenia, 24%; neutropenia, 16%; and anemia, 12%. Third-line Therapy A related poster focused on third-line therapy with bosutinib.2 The poster, presented by Hanna J. Khoury, MD, Winship Cancer Institute at Emory University in Atlanta, showed that bosutinib was effective and well tolerated as third-line therapy in 90 patients with chronic-phase CML in whom both first-line imatinib and second-line dasatinib had failed. In imatinib- and dasatinib-resistant patients, a complete CyR was reported in 6 (22%) of 27 evaluable patients, a complete hematologic response was reported in 18 (86%) of 21 evaluable patients, and a major molecular response was observed in 6 (27%) of 22 evaluable patients. Cytogenetic and molecular response rates were higher in the 23 patients who were on study due to intolerance to imatinib or dasatinib. The starting dose of bosutinib was 500 mg/d, with escalation to 600 mg if required. Median duration of treatment was 6.1 months in this ongoing phase II trial. Thus far, 3 patients have died and 14 have had disease progression. With a follow-up of 23 months, median overall survival was not reached in either resistant or intolerant patients. Responses were seen in patients with common BCR-ABL mutations, but not in those with T315I mutations. │ References 1. Cortes JE, Kantarjian H, Brummendorf T, et al: Safety and efficacy or bosutinib (SKI-606) in patients with chronic phase chronic myeloid leukemia following resistance or intolerance to imatinib. 2010 ASCO Annual Meeting. Abstract 6502 <http://www.asco.org/portal/site/ASCOv2/template.RAW/menuitem.a1c60e38cd6d5b 9f01ae0094ef37a01d/?javax.portlet.tpst=b2e033002b246c2828a46427ef37a01d_ws_R W&javax.portlet.prp_b2e033002b246c2828a46427ef37a01d_viewID=abst_detail_rawv iew&javax.portlet.begCacheTok=com.vignette.cachetoken&javax.portlet.endCache Tok=com.vignette.cachetoken&index=n&confID=74&abstractID=52917> . Presented June 7, 2010. 2. Khoury HJ, Kim D, Zaritskey A, et al: Safety and efficacy of third-line bosutinib in imatinib and dasatinib resistant or intolerant chronic phase chronic myeloid leukemia. 2010 ASCO Annual Meeting. Abstract 6514 <http://www.asco.org/portal/site/ASCOv2/template.RAW/menuitem.a1c60e38cd6d5b 9f01ae0094ef37a01d/?javax.portlet.tpst=b2e033002b246c2828a46427ef37a01d_ws_R W&javax.portlet.prp_b2e033002b246c2828a46427ef37a01d_viewID=abst_detail_rawv iew&javax.portlet.begCacheTok=com.vignette.cachetoken&javax.portlet.endCache Tok=com.vignette.cachetoken&index=n&confID=74&abstractID=52695> . Presented June 7, 2010 From: cmlhope@googlegroups.com [mailto:cmlhope@googlegroups.com] On Behalf Of maggy...@bellsouth.net Sent: Saturday, October 08, 2011 1:00 PM To: cmlhope@googlegroups.com Subject: Re: [CMLHope] OnControl what is SKI606? -- [CMLHope] A support group of http://cmlhope.com ------------------------------------------------- You received this message because you are subscribed to the Google Groups "CMLHope" group. 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