Sorafenib

A phase I dose de-escalation trial of oral sorafenib included pediatric patients with relapsed or refractory acute leukemia. Sorafenib was administered alone on days 1 to 7, and then in combination with clofarabine and high-dose cytarabine for 5 days, followed by single-agent sorafenib use until day 28.[32]

A phase I dose de-escalation trial of oral sorafenib included pediatric patients with relapsed or refractory acute leukemia. Sorafenib was administered alone on days 1 to 7, and then in combination with clofarabine and high-dose cytarabine for 5 days, followed by single-agent sorafenib use until day 28.[32]

The recommended phase II dose of sorafenib was determined to be 150 mg/m2 per dose (maximum dose, 300 mg) twice daily (n = 6) after patients experienced significant hand-foot skin reactions (grades 2–3 in 4 of 4 patients; grade 3 dose-limiting toxicities [DLTs] in 2 of 4 patients) at the initial 200 mg/m2 per dose, twice daily level (n = 4).

A phase I dose de-escalation trial of oral sorafenib included pediatric patients with relapsed or refractory acute leukemia. Sorafenib was administered alone on days 1 to 7, and then in combination with clofarabine and high-dose cytarabine for 5 days, followed by single-agent sorafenib use until day 28.[32]

Marrow blast reduction was seen in 10 of 12 total patients (4 of 5 patients with FLT3 ITD AML) at day 8.

A phase I dose de-escalation trial of oral sorafenib included pediatric patients with relapsed or refractory acute leukemia. Sorafenib was administered alone on days 1 to 7, and then in combination with clofarabine and high-dose cytarabine for 5 days, followed by single-agent sorafenib use until day 28.[32]

Of the 11 patients with AML, 6 patients achieved CR, 2 patients achieved CRi, and 1 patient achieved a partial remission (PR) on or after day 22.

A phase I dose de-escalation trial of oral sorafenib included pediatric patients with relapsed or refractory acute leukemia. Sorafenib was administered alone on days 1 to 7, and then in combination with clofarabine and high-dose cytarabine for 5 days, followed by single-agent sorafenib use until day 28.[32]

All five patients with FLT3 ITD achieved either CR or CRi.

A retrospective analysis examined 15 children with AML who received sorafenib for either prophylaxis (n = 6) or relapse (n = 9) after HSCT. Doses of sorafenib varied from 75 to 340 mg/m2 per day (median dose, 230 mg/m2) and was given alone in 11 of 15 patients.[33]

A retrospective analysis examined 15 children with AML who received sorafenib for either prophylaxis (n = 6) or relapse (n = 9) after HSCT. Doses of sorafenib varied from 75 to 340 mg/m2 per day (median dose, 230 mg/m2) and was given alone in 11 of 15 patients.[33]

Toxicity was seen in 11 patients, 7 of whom received doses higher than 200 mg/m2; adverse events included count suppression (n = 6), hand-foot skin reactions (n = 6), cardiac dysfunction (n = 2), and others.

A retrospective analysis examined 15 children with AML who received sorafenib for either prophylaxis (n = 6) or relapse (n = 9) after HSCT. Doses of sorafenib varied from 75 to 340 mg/m2 per day (median dose, 230 mg/m2) and was given alone in 11 of 15 patients.[33]

Of the seven patients who experienced DLTs, six patients were able to restart or continue sorafenib treatment after dose adjustments.

A retrospective analysis examined 15 children with AML who received sorafenib for either prophylaxis (n = 6) or relapse (n = 9) after HSCT. Doses of sorafenib varied from 75 to 340 mg/m2 per day (median dose, 230 mg/m2) and was given alone in 11 of 15 patients.[33]

Sorafenib had the greatest efficacy in patients with MRD pre- or post-HSCT (five of five patients remained disease free), whereas only one of the six patients who began sorafenib treatment for morphological recurrence remained in CR.

A retrospective analysis examined 15 children with AML who received sorafenib for either prophylaxis (n = 6) or relapse (n = 9) after HSCT. Doses of sorafenib varied from 75 to 340 mg/m2 per day (median dose, 230 mg/m2) and was given alone in 11 of 15 patients.[33]

Graft-versus-host disease (GVHD) was not exacerbated with sorafenib therapy.