New agents directed at molecular and other specific targets in clinical trials
New agents . | Targets . | Comments . |
|---|---|---|
| All-trans retinoic acid | PML-RARα | Has changed standard of care in APL; improves DFS and OS in newly diagnosed patients. |
| Arsenic trioxide | PML-RARα | Has changed standard of care in relapsed APL; induces high rate of hematologic and molecular CR; may cure some patients. |
| Gemtuzumab ozogamicin | CD33 | Modestly effective in patients with relapsed AML; role as additional agent in standard therapy currently being investigated. |
| Farnesyltransferase inhibitor | Farnesylation of lamin A and HJJ-2 | Modestly effective in high-risk patients newly diagnosed; role as adjunct to standard therapy under investigation. |
| FLT3 tyrosine kinase inhibitors | Internal tandem duplications of FLT3 | Most common gene mutation in AML. Some biologic activity in relapsed patients. Trials in combination with chemotherapy under way. |
| MDR modulators: cyclosporine, PSC833, zosuquidar | P-glycoprotein and other multidrug resistance proteins | In general, results disappointing. |
| Histone deacetylase inhibitors: phenylbutyrate, depsipeptide | Histone deacetylase | Clinical trials under way. |
| BCL-2 antisense deoxynucleotide | BCL-2 protein | Clinical trials under way. |
| Antiangiogenic agents | Vascular endothelial growth factor | Clinical trials under way. |
New agents . | Targets . | Comments . |
|---|---|---|
| All-trans retinoic acid | PML-RARα | Has changed standard of care in APL; improves DFS and OS in newly diagnosed patients. |
| Arsenic trioxide | PML-RARα | Has changed standard of care in relapsed APL; induces high rate of hematologic and molecular CR; may cure some patients. |
| Gemtuzumab ozogamicin | CD33 | Modestly effective in patients with relapsed AML; role as additional agent in standard therapy currently being investigated. |
| Farnesyltransferase inhibitor | Farnesylation of lamin A and HJJ-2 | Modestly effective in high-risk patients newly diagnosed; role as adjunct to standard therapy under investigation. |
| FLT3 tyrosine kinase inhibitors | Internal tandem duplications of FLT3 | Most common gene mutation in AML. Some biologic activity in relapsed patients. Trials in combination with chemotherapy under way. |
| MDR modulators: cyclosporine, PSC833, zosuquidar | P-glycoprotein and other multidrug resistance proteins | In general, results disappointing. |
| Histone deacetylase inhibitors: phenylbutyrate, depsipeptide | Histone deacetylase | Clinical trials under way. |
| BCL-2 antisense deoxynucleotide | BCL-2 protein | Clinical trials under way. |
| Antiangiogenic agents | Vascular endothelial growth factor | Clinical trials under way. |
FLT3 indicates Fms-like tyrosine kinase 3; MDR, multidrug resistance; BCL-2, B-CLL/lymphoma 2.