Researchers involved in an international study have reported that bosutinib (SKI606) is a new active kinase inhibitor for the treatment of patients with Philadelphia chromosome positive chronic myeloid leukemia (CML) or acute lymphoid leukemia (ALL). The details of this study were presented at the 2007 meeting of the American Society of Clinical Oncology in June.

Over the past 2 years, nilotinib and Sprycel® have emerged as potent kinase inhibitors active in patients with Philadelphia chromosome positive CML or ALL (See related news). Bosutinib, a 7-alkoxy-4-[(2,4-dichloro-5-methoxyphenyl)amino]-3-quinolinecarbonitrile, is a potent inhibitor of Src kinase activity. At ASCO 2007, the results of treating 69 patients with chronic phase of CML or ALL who had relapsed or were resistant to Gleevec with bosutinib were presented.

This is the first clinical report evaluating bosutinib. The first part of the study established that the appropriate dose was 500 mg/day. The phase II part of the study included 51 patients. Nineteen patients had no prior exposure to Gleevec, nilotinib or Sprycel. The major cytogenetic response rate for these 19 patients was 52%. In 9 patients with advanced leukemia, 4 had a complete hematological response and 2 had a major cytogenetic response. Bosutinib was also found to be effective in patients with defined Gleevec-resistant mutations.

These authors concluded that bosutinib was active across a range of mutations. Side effects included diarrhea, nausea, vomiting and abdominal pain. Grade 3/4 toxicities occurred in 5% of patients with chronic phase of CML. Dose reductions were made in 17 of the 69 patients studied.  

Comments: Bosutinib appears to be the third second generation kinase inhibitior to show activity in Philadelphia chromosome positive CML and ALL.

Refrences: Gambacorti-Passerini C, Blummedorf T, Kantarjian H, et al. Bosutinib (SKI-606) exhibits clinical activity in patients with Philadelphia chromosome positive CML or AML who failed imatinib. Proceedings from the American Society of Clinical Onlcology Conference. Chicago/IL.  Abstract # 7006.

Related News:

Nilotinib Effective in Newly Diagnosed Patients with CML (01/09/2007)

Nilotinib Effective for Treatment of Gleevec®-Resistant CML (06/26/2006)

Sprycel® Effective after Gleevec® Failure in Patients with CML in Chronic Phase (03/14/2007)

Sprycel® Superior to High-Dose Gleevec for Gleevec-Resistant CML (01/18/2007)