Three new drugs for acute lymphoblastic leukemia: nelarabine, clofarabine, and forodesine.
The search for more effective and safer anti-leukemia therapies has led to the identification of several new agents that show activity against specific types of acute lymphoblastic leukemia (ALL). Recently, three novel purine nucleoside analogues (nelarabine, clofarabine, and forodesine) have shown promising activity in patients with relapsed or refractory ALL. Of these, nelarabine has shown clinically meaningful benefit in patients with T-cell ALL, with overall response rates ranging from 33% to 60%, the induction of durable complete remissions, and an overall 1-year survival rate of 28% in adults. Clofarabine has also shown promising clinical activity in pediatric patients, with an overall response rate of 30%, and some patients are able to proceed to allogeneic hematopoietic cell transplantation. Forodesine is the most recent novel agent, with a unique mechanism that has shown single-agent activity in relapsed and refractory T- and B-cell leukemias and cutaneous lymphomas. Although clinical experience is limited, treatment-related toxicities appear to be mild. The rationale, pharmacology, and clinical experience to date with these agents in the treatment of patients with refractory acute leukemia are reviewed, with a highlight on ALL.
Larson
Richard A
RA
Hematologic Malignancies Program, Section of Hematology/Oncology, Department of Medicine, Cancer Research Center, The University of Chicago, Chicago, IL 60637, USA. rlarson@medicine.bsd.uchicago.edu
D000227:Adenine Nucleotides / Q000493:pharmacokinetics / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001087:Arabinonucleosides / Q000493:pharmacokinetics / Q000494:pharmacology*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D000077866:Clofarabine; D006801:Humans; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D011684:Purine Nucleosides / Q000493:pharmacokinetics / Q000494:pharmacology*; D011683:Purine-Nucleoside Phosphorylase / Q000037:antagonists & inhibitors / Q000187:drug effects*; D011744:Pyrimidinones / Q000493:pharmacokinetics / Q000494:pharmacology*
D000227:Adenine Nucleotides; D000970:Antineoplastic Agents; D001087:Arabinonucleosides; D011684:Purine Nucleosides; D011744:Pyrimidinones; C113101:forodesine; C104457:nelarabine; D000077866:Clofarabine; D011683:Purine-Nucleoside Phosphorylase