The Difference Between Dasatinib/Startase and Imatinib

Dasatinib(Dasatinib) and imatinib (Imatinib) are both tyrosine kinase inhibitors used to treat chronic myelomonocytic leukemia (CML) and other types of leukemia. However, they have some significant differences in their mechanisms of action, indications, drug resistance, and safety of use. Although they have similar therapeutic purposes, both drugs have their own advantages and limitations in clinical practice.

1. Differences in mechanisms of action and targets

Imatinib is a first-generation tyrosine kinase inhibitor (TKI) that inhibits the tyrosine kinase activity of BCR-ABL fusion protein, thereby preventing the proliferation of cancer cells. The BCR-ABL fusion gene is a causative gene in chronic myeloid leukemia (CML) and certain types of acute lymphoblastic leukemia (ALL). Imatinib effectively treats these diseases through this mechanism.

In contrast, dasatinib is a second-generation tyrosine kinase inhibitor. As an improved version of imatinib, it can not only inhibitBCR-ABL protein, but also effectively inhibit other tyrosine kinases including SRC family kinases. Therefore, dasatinib has a wider range of targets and can target more pathogenic mechanisms. Dasatinib not only inhibits the BCR-ABL protein, but also inhibits multiple other related molecular pathways, which makes it more effective in some drug-resistant patients.

2. Indications and clinical applications

Imatinib has become the standard drug for the treatment of chronic myelomonocytic leukemia (CML) and is widely used in various types of leukemia, especially in the early stages. It is particularly effective for CML patients, helping to control the progression of leukemia and reduce the proliferation of leukemia cells, and has a long history of clinical use. Imatinib is also used to treat other types of cancer, such as gastrointestinal stromal tumor (GIST) and Phillips chromosome-positive acute lymphoblastic leukemia (ALL).

The indications for dasatinib are similar to those of imatinib, but it is often used as a follow-up treatment, especially when patients develop resistance or intolerance to imatinib. Because dasatinib can overcome the resistance caused by certain BCR-ABL fusion gene mutations, it has important therapeutic significance for patients who are ineffective or resistant to imatinib treatment. Especially in patients with common resistance mutations such as the T315I mutation to imatinib, dasatinib often provides effective treatment.

3. Drug resistance and side effects

Imatinib has been used to treat a variety of leukemias such as CML since its launch, and has achieved significant clinical efficacy. However, over time, some patients develop drug resistance, especially when the BCR-ABL gene is mutated. The most common mutation is the T315I mutation, which causes imatinib to lose its inhibitory effect. Therefore, one of the main limitations of imatinib is the existence of certain resistance.

Dasatinib, as the second generationTKI, has better solved the problem of resistance to imatinib in some mutations. It still has a certain inhibitory effect on a variety of BCR-ABL mutations, such as T315I mutation. Due to its inhibitory effect on multiple kinases, dasatinib has low resistance, especially in some patients who are resistant to imatinib, and dasatinib can be used as an alternative treatment option.

However, the side effects of dasatinib are also cause for concern. Common adverse reactions include edema, musculoskeletal pain, bone marrow suppression (such as anemia, leukopenia), and QT interval prolongation. Edema and cardiovascular problems, in particular, require close monitoring during treatment. In contrast, imatinib has mild side effects. Common adverse reactions include mild edema, indigestion and mild bone marrow suppression. It is generally well tolerated, but gastrointestinal symptoms may also occur after long-term use.

References:https://www.nejm.org/doi/full/10.1056/NEJMoa1002315