Early Phase II results show bosutinib safe, effective for CML

December 11, 2007

ATLANTA - A new drug for chronic myelogenous leukemia works for patients who have developed resistance to frontline therapy and causes fewer side effects than other medications in its class, a research team led by scientists at The University of Texas M. D. Anderson Cancer Center reports at the 49th annual meeting of the American Society of Hematology.

"Bosutinib has shown good efficacy and very little toxicity compared to other tyrosine kinase inhibitors at this stage of the clinical trial," says lead researcher Jorge Cortes, M.D., professor in M. D. Anderson's Department of Leukemia.

Bosutinib, developed by Wyeth Pharmaceuticals, is being tested in patients in the early or chronic phase of CML whose disease has become resistant to imatinib or who have become intolerant of imatinib's side effects.

So far, 98 patients have enrolled in the relatively new clinical trial, with median duration of treatment at 5.1 months.

Among 23 evaluable patients who had become resistant to imatinib, 17 (74 percent) achieved a complete hematological response - normal blood counts. Of 36 evaluable for cytogenetic response - reduction of the abnormal chromosome that causes the disease - 15 had a major response and 12 of those had a complete response, or absence, of the chromosome.

"These responses are comparable to other drugs at a similar stage of follow-up," Cortes says.

Interestingly, a small number of patients who had also become resistant to second-line treatments nilotinib and dasatinib derived some benefit from taking the new drug. Out of eight such patients, three achieved complete hematologic response and two achieved major cytogenetic response.

The most common side effects were low-grade nausea, vomiting and diarrhea, which improved greatly three or four weeks into therapy. Higher grade side effects such as low counts of platelets, white or red blood cells ranged from 1 to 9 percent of patients. Fluid build-up in the lungs and other organs occurred in only 12 patients and was of low grade.

Cortes says the researchers suspect that the low grade and frequency of side effects is probably a result of the drug's specificity in the proteins that it targets. Bosutinib inhibits SRC and ABL proteins but does not affect platelet derived growth factor receptor or C-Kit, two similar kinases that are affected by other CML drugs.

CML is caused by the Bcr-Abl protein, which results from a chromosomal abnormality called the Philadelphia Chromosome. Bcr-Abl is a tyrosine kinase that fuels an overabundance of white blood cells and immature stem cells called blasts that crowd out red blood cells and platelets.

Tyrosine kinases are a specialized subgroup of protein kinases, which regulate protein behavior by attaching phosphate groups to proteins or small molecules. Bosutinib, like imatinib (Gleevec(r)), dasatinib (Sprycel(r)) and nilotinib (Tasigna(r)), is a tyrosine kinase inhibitor.

The researchers also found that bosutinib is effective against a variety of Bcr-Abl mutants that cause CML and conclude that the drug is effective in imatinib-resistant patients with chronic CML across a range of mutations and after the failure of other tyrosine kinase inhibitors.
-end-
Co-authors with Cortes are Hagop Kantarjian, M.D., of M. D. Anderson's Department of Leukemia; Tim Bruemmendorf, M.D., University of Hamburg; H. Jean Khoury, M.D., and Becker Hewes, M.D. of Emory University; Gianantonio Rosti, University of Bologna, Italy; Thomas Fischer, M.D., Johannes Gutenberg University, Mainz, Germany; L. Tornaghi; E.C. Martin of Wyeth Research; and Carlo Gambacorti-Passerini, M.D., and Lucia Tornaghi, both of University of Milano-Bicocca.

University of Texas M. D. Anderson Cancer Center

Related Proteins Articles from Brightsurf:

New understanding of how proteins operate
A ground-breaking discovery by Centenary Institute scientists has provided new understanding as to the nature of proteins and how they exist and operate in the human body.

Finding a handle to bag the right proteins
A method that lights up tags attached to selected proteins can help to purify the proteins from a mixed protein pool.

Designing vaccines from artificial proteins
EPFL scientists have developed a new computational approach to create artificial proteins, which showed promising results in vivo as functional vaccines.

New method to monitor Alzheimer's proteins
IBS-CINAP research team has reported a new method to identify the aggregation state of amyloid beta (Aβ) proteins in solution.

Composing new proteins with artificial intelligence
Scientists have long studied how to improve proteins or design new ones.

Hero proteins are here to save other proteins
Researchers at the University of Tokyo have discovered a new group of proteins, remarkable for their unusual shape and abilities to protect against protein clumps associated with neurodegenerative diseases in lab experiments.

Designer proteins
David Baker, Professor of Biochemistry at the University of Washington to speak at the AAAS 2020 session, 'Synthetic Biology: Digital Design of Living Systems.' Prof.

Gone fishin' -- for proteins
Casting lines into human cells to snag proteins, a team of Montreal researchers has solved a 20-year-old mystery of cell biology.

Coupled proteins
Researchers from Heidelberg University and Sendai University in Japan used new biotechnological methods to study how human cells react to and further process external signals.

Understanding the power of honey through its proteins
Honey is a culinary staple that can be found in kitchens around the world.

Read More: Proteins News and Proteins Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.