Dasatinib may be effective option for pediatric leukemia

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Dasatinib may be effective option for pediatric leukemia

by Walter

Hem/Onc Today CORRESPONDENT

March 2007

ORLANDO, Fla. - For pediatric and adolescent patients with both Philadelphia

(Ph)+ and Ph- leukemias, dasatinib may be an effective and tolerable

treatment option, according to preliminary dose-finding study data presented

at the 48th Annual Meeting of the American Society of Hematology.

Dasatinib (Sprycel, Bristol-Myers Squibb) has demonstrated efficacy in

imatinib-resistant or -intolerant Ph+ disease and is approved in the United

States and Europe for adult chronic myeloid leukemia and Ph+ acute

lymphocytic leukemia.

Few effective treatment options for pediatric patients with relapsed or

refractory leukemias are available, said Christian M. Zwaan, MD, pediatric

oncologist at the Sophia Children's Hospital in Rotterdam, The Netherlands.

Even though pediatric study of pharmacologic agents generally starts at 80%

of the adult recommended dose, children can often tolerate higher doses than

adults because they are healthier and lack the cardiac and renal problems

which often limit adult dosing, according to Zwaan.

The intent of Zwaan's study is to determine a recommended dasatinib dose by

disease stratum in children and adolescents with relapsed or refractory

leukemia.

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Patients and dosing

The study included 22 children (aged 1 to 20) with imatinib-resistant or

-intolerant CML, post-imatinib relapsed Ph+ ALL or Ph- ALL or acute

myelogenous leukemia in more than two relapses. Eleven patients had prior

imatinib therapy; 16 of the patients had received prior chemotherapy; and

nine had prior stem cell transplants.

Patients were stratified into four groups according to disease severity,

with the first stratum including patients with chronic phase (n=2) and the

fourth stratum including those with more than two relapses or refractory

disease after more than two prior induction regimens (n=11).

" What we want to do is to give dasatinib up-front on top of chemotherapy to

try to improve overall survival before the patients relapse. "

- Christian M. Zwaan, MD

The median daily dose, with dose escalations proceeding at the time of this

report, is 77 mg/m2, and the median duration of therapy is 0.72 months.

Initial doses were 80 mg/m2 per day in six patients and 60 mg/m2 per day in

the rest.

Among the 11 patients in the first three strata, six had hematologic and/or

cytogenetic responses, four of them with complete hematologic and

cytogenetic responses. Three patients in the second stratum achieved

clearance of cerebrospinal fluid blasts. Two of eleven in the fourth

stratum, one with Ph- AML and one with Ph- ALL, achieved a significant

decrease in white blood cells.

Response duration ranges from 21 to 217 or more days. Time to response

ranges from 21 to 63 days, with time to best response between seven and 98

or more days.

Zwaan noted that two patients have been responding for longer than seven

months, and others have relapsed after as little as two weeks. " While there

were some complete remissions, all patients are expected to relapse because

this is monotherapy, " Zwaan said in an interview.

" What we want to do is to give dasatinib up-front on top of chemotherapy to

try to improve overall survival before the patients relapse, " he said.

Some activity, Zwann said, was observed for dasatinib in Ph- leukemias. " So

we think the indication may be broader than just Ph+ disease. "

Dasatinib was generally well-tolerated and had a favorable safety profile.

Nonhematologic toxicities were mostly mild to moderate in severity. One

patient had a pleural effusion that responded to diuretics, steroids and

drug interruption. Cytopenias were infrequent, occurring in only one patient

who had been heavily pretreated (including stem cell transplant).

" In this preliminary analysis, dasatinib showed efficacy in pediatric

patients with Ph+ and Ph- leukemias, " Zwaan said.

The next studies will be conducted with dasatinib in conjunction with

chemotherapy.

For more information:

* Chromik J, Pfeifer H, Wunderle L, et al. Sustained molecular

responses to dasatanib (SPRYCEL) in patients with Philadelphia

chromosome-positive (Ph(+)) acute lymphoblastic leukemia (ALL) or lymphoid

blast phase (LyBP) chronic myeloid leukemia after imatinib (IM) failure: a

single-center experience. Abstract 285. Presented at: 48th Annual Meeting of

the American Society of Hematology. Dec. 9-12, 2006; Orlando, Fla.

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Zavie (age 68)

67 Shoreham Avenue

Ottawa, Canada, dxd AUG/99

INF OCT/99 to FEB/00, CHF

No meds FEB/00 to JAN/01

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