Efficacy and safety of thalidomide in patients with acute myeloid leukemia

• Published in: Blood 2002-02, Vol.99 (3), p.834-839
• Main Authors: Steins, Martin B., Padró, Teresa, Bieker, Ralf, Ruiz, Sandra, Kropff, Martin, Kienast, Joachim, Kessler, Torsten, Buechner, Thomas, Berdel, Wolfgang E., Mesters, Rolf M.
• Format: Article
• Language: English
• Subjects: Acute Disease; Aged; Aged, 80 and over; Angiogenesis Inhibitors - administration & dosage; Angiogenesis Inhibitors - pharmacokinetics; Angiogenesis Inhibitors - toxicity; Antineoplastic agents; Biological and medical sciences; Bone Marrow - blood supply; Bone Marrow - drug effects; Bone Marrow - pathology; Chemotherapy; Dose-Response Relationship, Drug; Female; Growth Substances - metabolism; Hematologic and hematopoietic diseases; Hemoglobins - metabolism; Humans; Leukemia, Myeloid - complications; Leukemia, Myeloid - drug therapy; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Leukemic Infiltration - drug therapy; Male; Medical sciences; Middle Aged; Neovascularization, Pathologic - drug therapy; Pharmacology. Drug treatments; Platelet Count; Thalidomide - pharmacokinetics; Thalidomide - pharmacology; Thalidomide - toxicity; Therapeutic Equivalency; Treatment Outcome
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V99.3.834

Emerging data suggest an involvement of angiogenesis in the pathophysiology of acute myeloid leukemia (AML). Thus, antiangiogenic therapy could constitute a novel strategy for the treatment of AML. To test this hypothesis, a phase I/II dose-escalating trial was performed to study the safety and efficacy of thalidomide, a putative inhibitor of angiogenesis, in 20 patients with AML. Thirteen patients were assessable for both toxicity and response, tolerating a maximum dose of 200 to 400 mg daily for at least 1 month. Seven patients had to be prematurely withdrawn from drug administration owing to progressive disease and death (3 patients), personal decision (2 patients), or inability to tolerate thalidomide (2 patients). Overall, adverse events were fatigue, constipation, rash, and neuropathy (grade 1 to 2 in most patients). In 4 patients, a partial response, defined as reduction of at least 50% in the blast cell infiltration of the bone marrow accompanied by increases in platelet counts and hemoglobin values, was observed. One additional patient showed a hematologic improvement without fulfilling the criteria of a partial response. The responses lasted a median of 3 months (range, 1-8 months). In parallel, microvessel densities significantly decreased in these 5 patients during treatment with thalidomide (P < .05). This decrease was accompanied by declining plasma levels of basic fibroblast growth factor, one of the most potent angiogenic growth factors. In conclusion, single-agent thalidomide has antiangiogenic and antileukemic activity in AML, although a causal relationship between both effects has still to be proven.