title: Myelosuppression in patients benefiting from imatinib with hydroxyurea for recurrent malignant gliomas.
abstract: Reports suggest reasonable efficacy and minimal myelosuppression from combination imatinib and hydroxyurea for recurrent malignant glioma. We retrospectively reviewed 16 patients treated with this regimen who were evaluable for toxicity; 14 were also evaluable for response. The incidence of grade 3-4 hematologic toxicity was 25%. The best radiographic response, by Macdonald criteria, was partial response (PR) in three patients (21%), stable disease (SD) in four (29%), and progressive disease (PD) in seven (50%). One patient with a PR developed therapy-limiting hematologic toxicity on day 19 of treatment, progressing to grade 4 on day 64, and persisting until death on day 127 despite discontinuing both drugs. Another patient with PR and two of four patients with SD also developed grade 3 hematologic toxicity. All patients with grade 3-4 hematologic toxicity had disease control (PR or SD) as best radiographic response, whereas none with PD suffered grade 3-4 hematologic toxicity. Combining imatinib with hydroxyurea is effective in some patients with malignant glioma. However, myelosuppression can persist for months after discontinuing the regimen, precluding further chemotherapy. Disease control may also correlate with hematologic toxicity (p = 0.08), suggesting that glioma and marrow stem cells may share a common sensitivity to this chemotherapy regimen.
authors.affiliation: Department of Neurology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
authors.forename: Gaurav D
authors.initials: GD
authors.lastname: Shah
authors.forename: Joel S
authors.initials: JS
authors.lastname: Silver
authors.forename: Steven S
authors.initials: SS
authors.lastname: Rosenfeld
authors.forename: Igor T
authors.initials: IT
authors.lastname: Gavrilovic
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Abrey
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Lassman
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D001549:Benzamides; D001853:Bone Marrow / Q000187:drug effects; D001855:Bone Marrow Diseases / Q000139:chemically induced* / Q000150:complications; D001932:Brain Neoplasms / Q000150:complications / Q000188:drug therapy*; D005909:Glioblastoma / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D019384:Nucleic Acid Synthesis Inhibitors / Q000008:administration & dosage; D010879:Piperazines / Q000008:administration & dosage; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000008:administration & dosage; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D001549:Benzamides; D019384:Nucleic Acid Synthesis Inhibitors; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D006918:Hydroxyurea