No influence of the polymorphisms <it>CYP2C19 </it>and <it>CYP2D6 </it>on the efficacy of cyclophosphamide, thalidomide, and bortezomib in patients with Multiple Myeloma
<p>Abstract</p> <p>Background</p> <p>The response to treatment varies among patients with multiple myeloma and markers for prediction of treatment outcome are highly needed. Bioactivation of cyclophosphamide and thalidomide, and biodegradation of bortezomib, is dependen...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2010-08-01
|
| Series: | BMC Cancer |
| Online Access: | http://www.biomedcentral.com/1471-2407/10/404 |
| _version_ | 1811286292573454336 |
|---|---|
| author | Vogel Ulla Gregersen Henrik Gimsing Peter Abildgaard Niels Andersen Niels F Klausen Tobias W Søeby Karen Vangsted Annette J Werge Thomas Rasmussen Henrik B |
| author_facet | Vogel Ulla Gregersen Henrik Gimsing Peter Abildgaard Niels Andersen Niels F Klausen Tobias W Søeby Karen Vangsted Annette J Werge Thomas Rasmussen Henrik B |
| author_sort | Vogel Ulla |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>The response to treatment varies among patients with multiple myeloma and markers for prediction of treatment outcome are highly needed. Bioactivation of cyclophosphamide and thalidomide, and biodegradation of bortezomib, is dependent on cytochrome P450 metabolism. We explored the potential influence of different polymorphisms in the CYP enzymes on the outcome of treatment.</p> <p>Methods</p> <p>Data was analyzed from 348 patients undergoing high-dose treatment and stem cell support in Denmark in 1994 to 2004. Clinical information on relapse treatment in 243 individual patients was collected. The patients were genotyped for the non-functional alleles <it>CYP2C19*2 </it>and <it>CYP2D6*3</it>, <it>*4</it>, <it>*5 </it>(gene deletion), <it>*6</it>, and <it>CYP2D6 </it>gene duplication.</p> <p>Results</p> <p>In patients who were treated with bortezomib and were carriers of one or two defective <it>CYP2D6 </it>alleles there was a trend towards a better time-to-next treatment. We found no association between the number of functional <it>CYP2C19 </it>and <it>CYP2D6 </it>alleles and outcome of treatment with cyclophosphamide or thalidomide. Neither was the number of functional <it>CYP2C19 </it>and <it>CYP2D6 </it>alleles associated with neurological adverse reactions to thalidomide and bortezomib.</p> <p>Conclusion</p> <p>There was no association between functional <it>CYP2C19 </it>and <it>CYP2D6 </it>alleles and treatment outcome in multiple myeloma patients treated with cyclophosphamide, thalidomide or bortezomib. A larger number of patients treated with bortezomib are needed to determine the role of <it>CYP2D6 </it>alleles in treatment outcome.</p> |
| first_indexed | 2024-04-13T02:57:30Z |
| format | Article |
| id | doaj.art-24cd268eb7e84566a16eb9b8018b95fa |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-13T02:57:30Z |
| publishDate | 2010-08-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-24cd268eb7e84566a16eb9b8018b95fa2022-12-22T03:05:34ZengBMCBMC Cancer1471-24072010-08-0110140410.1186/1471-2407-10-404No influence of the polymorphisms <it>CYP2C19 </it>and <it>CYP2D6 </it>on the efficacy of cyclophosphamide, thalidomide, and bortezomib in patients with Multiple MyelomaVogel UllaGregersen HenrikGimsing PeterAbildgaard NielsAndersen Niels FKlausen Tobias WSøeby KarenVangsted Annette JWerge ThomasRasmussen Henrik B<p>Abstract</p> <p>Background</p> <p>The response to treatment varies among patients with multiple myeloma and markers for prediction of treatment outcome are highly needed. Bioactivation of cyclophosphamide and thalidomide, and biodegradation of bortezomib, is dependent on cytochrome P450 metabolism. We explored the potential influence of different polymorphisms in the CYP enzymes on the outcome of treatment.</p> <p>Methods</p> <p>Data was analyzed from 348 patients undergoing high-dose treatment and stem cell support in Denmark in 1994 to 2004. Clinical information on relapse treatment in 243 individual patients was collected. The patients were genotyped for the non-functional alleles <it>CYP2C19*2 </it>and <it>CYP2D6*3</it>, <it>*4</it>, <it>*5 </it>(gene deletion), <it>*6</it>, and <it>CYP2D6 </it>gene duplication.</p> <p>Results</p> <p>In patients who were treated with bortezomib and were carriers of one or two defective <it>CYP2D6 </it>alleles there was a trend towards a better time-to-next treatment. We found no association between the number of functional <it>CYP2C19 </it>and <it>CYP2D6 </it>alleles and outcome of treatment with cyclophosphamide or thalidomide. Neither was the number of functional <it>CYP2C19 </it>and <it>CYP2D6 </it>alleles associated with neurological adverse reactions to thalidomide and bortezomib.</p> <p>Conclusion</p> <p>There was no association between functional <it>CYP2C19 </it>and <it>CYP2D6 </it>alleles and treatment outcome in multiple myeloma patients treated with cyclophosphamide, thalidomide or bortezomib. A larger number of patients treated with bortezomib are needed to determine the role of <it>CYP2D6 </it>alleles in treatment outcome.</p>http://www.biomedcentral.com/1471-2407/10/404 |
| spellingShingle | Vogel Ulla Gregersen Henrik Gimsing Peter Abildgaard Niels Andersen Niels F Klausen Tobias W Søeby Karen Vangsted Annette J Werge Thomas Rasmussen Henrik B No influence of the polymorphisms <it>CYP2C19 </it>and <it>CYP2D6 </it>on the efficacy of cyclophosphamide, thalidomide, and bortezomib in patients with Multiple Myeloma BMC Cancer |
| title | No influence of the polymorphisms <it>CYP2C19 </it>and <it>CYP2D6 </it>on the efficacy of cyclophosphamide, thalidomide, and bortezomib in patients with Multiple Myeloma |
| title_full | No influence of the polymorphisms <it>CYP2C19 </it>and <it>CYP2D6 </it>on the efficacy of cyclophosphamide, thalidomide, and bortezomib in patients with Multiple Myeloma |
| title_fullStr | No influence of the polymorphisms <it>CYP2C19 </it>and <it>CYP2D6 </it>on the efficacy of cyclophosphamide, thalidomide, and bortezomib in patients with Multiple Myeloma |
| title_full_unstemmed | No influence of the polymorphisms <it>CYP2C19 </it>and <it>CYP2D6 </it>on the efficacy of cyclophosphamide, thalidomide, and bortezomib in patients with Multiple Myeloma |
| title_short | No influence of the polymorphisms <it>CYP2C19 </it>and <it>CYP2D6 </it>on the efficacy of cyclophosphamide, thalidomide, and bortezomib in patients with Multiple Myeloma |
| title_sort | no influence of the polymorphisms it cyp2c19 it and it cyp2d6 it on the efficacy of cyclophosphamide thalidomide and bortezomib in patients with multiple myeloma |
| url | http://www.biomedcentral.com/1471-2407/10/404 |
| work_keys_str_mv | AT vogelulla noinfluenceofthepolymorphismsitcyp2c19itanditcyp2d6itontheefficacyofcyclophosphamidethalidomideandbortezomibinpatientswithmultiplemyeloma AT gregersenhenrik noinfluenceofthepolymorphismsitcyp2c19itanditcyp2d6itontheefficacyofcyclophosphamidethalidomideandbortezomibinpatientswithmultiplemyeloma AT gimsingpeter noinfluenceofthepolymorphismsitcyp2c19itanditcyp2d6itontheefficacyofcyclophosphamidethalidomideandbortezomibinpatientswithmultiplemyeloma AT abildgaardniels noinfluenceofthepolymorphismsitcyp2c19itanditcyp2d6itontheefficacyofcyclophosphamidethalidomideandbortezomibinpatientswithmultiplemyeloma AT andersennielsf noinfluenceofthepolymorphismsitcyp2c19itanditcyp2d6itontheefficacyofcyclophosphamidethalidomideandbortezomibinpatientswithmultiplemyeloma AT klausentobiasw noinfluenceofthepolymorphismsitcyp2c19itanditcyp2d6itontheefficacyofcyclophosphamidethalidomideandbortezomibinpatientswithmultiplemyeloma AT søebykaren noinfluenceofthepolymorphismsitcyp2c19itanditcyp2d6itontheefficacyofcyclophosphamidethalidomideandbortezomibinpatientswithmultiplemyeloma AT vangstedannettej noinfluenceofthepolymorphismsitcyp2c19itanditcyp2d6itontheefficacyofcyclophosphamidethalidomideandbortezomibinpatientswithmultiplemyeloma AT wergethomas noinfluenceofthepolymorphismsitcyp2c19itanditcyp2d6itontheefficacyofcyclophosphamidethalidomideandbortezomibinpatientswithmultiplemyeloma AT rasmussenhenrikb noinfluenceofthepolymorphismsitcyp2c19itanditcyp2d6itontheefficacyofcyclophosphamidethalidomideandbortezomibinpatientswithmultiplemyeloma |