A phase I/II study of sorafenib in combination with low dose cytarabine in elderly patients with acute myeloid leukemia or high-risk myelodysplastic syndrome from the National Cancer Institute of Canada Clinical Trials Group: trial IND.186.
Sorafenib is active in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The National Cancer Institute of Canada (NCIC) Clinical Trials Group initiated a phase I/II study of the combination of sorafenib with cytarabine in older patients with AML or high-risk MDS who were unsuitable for intensive chemotherapy. FLT3 mutational status was determined in all patients. Twenty-one patients were enrolled (four MDS, 17 AML) with a median age of 77 years. The recommended phase II dose (RP2D) was cytarabine 10 mg bid days 1-10 and sorafenib 600 mg/day days 2-28. Dose-limiting toxicities were fatigue, sepsis and skin rash. Of 15 evaluable patients treated at the RP2D, two patients responded. The overall response rate for eligible patients was 10%. FLT3 mutations were found in only three patients. We conclude that this combination of sorafenib and cytarabine has limited activity in this unselected cohort of elderly patients with AML/MDS in which FLT3 mutations seemed underrepresented.
Queen Elizabeth II Health Sciences Centre, Halifax, NS, Canada. david.macdonald@cdha.nshealth.ca
David A
DA
Macdonald
Sarit E
SE
Assouline
Joseph
J
Brandwein
Suzanne
S
Kamel-Reid
Elizabeth A
EA
Eisenhauer
Stephen
S
Couban
Stephen
S
Caplan
Alison
A
Foo
Wendy
W
Walsh
Brian
B
Leber
D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D003561:Cytarabine / Q000008:administration & dosage; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000235:genetics; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives*; D010671:Phenylurea Compounds / Q000008:administration & dosage*; D000077157:Sorafenib; D016896:Treatment Outcome; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
D010671:Phenylurea Compounds; D003561:Cytarabine; D009536:Niacinamide; D000077157:Sorafenib; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3