An overview of the dose management of dasatinib

This study reviewed evidence on the dose management of dasatinib (Sprycel) for chronic myeloid leukemia (CML).

Tyrosine kinase inhibitor (TKI) therapy is a standard first-line treatment for CML. Many patients achieve optimal response to TKI therapy and have a near-normal life expectancy. However, this response is lost when TKI therapy is stopped. Patients will typically undergo life-long TKI therapy. Treatment should therefore be optimized to minimize side effects while maintaining the response.

Dasatinib is a recently developed TKI. Early studies are showing good effectiveness. Dasatinib is currently approved at 2 doses. It is administered at 100 mg once daily for newly diagnosed CML. Patients with relapsed (return of the disease) CML or high-risk factors such as certain genetic abnormalities may receive 140 mg once daily. The aim of this study was to review evidence on the dose management of dasatinib.

One study reduced the dosage of dasatinib from 100 to 50 mg per day in patients who experienced mild to serious side effects. 34% had their dosage reduced at 6 months. At 6 months, 25 patients (78%) achieved complete cytogenetic response (little or no abnormal chromosomes in the blood or bone marrow). 13 patients (40%) achieved major molecular response (little or no genetic abnormalities in the blood or bone marrow).

Another study reported similar response rates between patients with a reduced dasatinib dosage (50 and 63 mg per day) and patients receiving 100 mg per day. Pleural effusion is a common side effect of dasatinib. This is when excess fluid builds around the lung. This was managed effectively with the reduced dasatinib dosage.

One study examined dasatinib dose reduction in 289 patients with newly diagnosed CML. Those with high levels of dasatinib in their blood had the dosage reduced by 20 mg every 15 days to 40 mg per day. These patients showed a reduced risk of pleural effusion without affecting treatment response. By 24 months, about 88% of patients who had their dosage lowered achieved major molecular response. 39% achieved complete molecular remission.

Intermittent dosing with dasatinib was examined in 31 patients not responding to imatinib (Gleevec), a first-generation TKI. Patients received 3 to 5 days of dasatinib, followed by 2 to 4 days of no treatment. 89% of patients achieved at least major molecular response. A larger study included 176 patients to receive reduced or intermittent dosing with a second-generation TKI (dasatinib or nilotinib [Tasigna]). No significant difference in treatment response were found between the two strategies.

Treatment-free remission refers to being free from molecular recurrence (return of disease) after TKI discontinuation. It is the main goal of CML treatment. However, most CML patients will undergo a life-long duration of treatment. In a small study of 34 patients, second-generation TKIs (dasatinib and nilotinib) were safely discontinued. The 12-month probability of maintaining stable major molecular response was 58%. No patient experienced disease progression.

In another study, 41% of patients showing early response to dasatinib were in treatment-free remission at 12 months. Treatment-free remission rates in another study were 63% at 12 months and 54% at 48 months. All patients had reached deep molecular response for at least 2 years with dasatinib or nilotinib.

Authors concluded that dasatinib dose reductions or ‘drug holidays’ are suitable strategies to control side effects while maintaining treatment response. Certain patients are able to safely discontinue dasatinib therapy. However, more studies are needed to help predict which patients will benefit from dasatinib discontinuation.