Document Detail


Phase I/II study of subcutaneous homoharringtonine in patients with chronic myeloid leukemia who have failed prior therapy.
MedLine Citation:
PMID:  17154172     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Homoharringtonine (HHT) is a cephalotaxus alkaloid that inhibits the synthesis of proteins leading to apoptosis. Intravenous HHT has demonstrated activity in patients with chronic myeloid leukemia (CML) after failure with interferon. METHODS: A Phase I study was completed of subcutaneous (s.c.) HHT in patients with CML in accelerated or blast phases and demonstrated efficacy and good tolerance at the same doses used by intravenous (i.v.) administration. The maximal tolerated dose (MTD) was 1.25 mg/m(2) s.c. twice daily. The cohort was then expanded to treated at the MTD to include patients in late chronic phase CML after imatinib failure. Therapy consisted of an i.v. loading dose of HHT 2.5 mg/m(2) over 24 hours, followed by 1.25 mg/m(2) s.c. twice daily for 14 days every 28 days until remission, then for 7 days every 28 days. Six patients (median age, 53 years) who had failed imatinib were treated and 5 were evaluable. Patients received a median of 4.5 courses of s.c. HHT. RESULTS: Complete hematologic remission was obtained in all 5 evaluable patients and 3 had cytogenetic (CG) responses: 1 complete and 2 minor. The 2 patients with BCR-ABL kinase domain mutations at the start of therapy with HHT had a CG response and in both instances the mutations became undetectable. All patients developed myelosuppression and 3 had their HHT dose reduced due to prolonged neutropenia. Nonhematologic toxicity was mild and manageable. CONCLUSIONS: Subcutaneous HHT is well tolerated and may have clinical activity in patients with CML after imatinib failure.
Authors:
Alfonso Quintás-Cardama; Hagop Kantarjian; Guillermo Garcia-Manero; Susan O'Brien; Stefan Faderl; Zeev Estrov; Francis Giles; Anthony Murgo; Nakia Ladie; Srdan Verstovsek; Jorge Cortes
Publication Detail:
Type:  Clinical Trial, Phase I; Clinical Trial, Phase II; Journal Article    
Journal Detail:
Title:  Cancer     Volume:  109     ISSN:  0008-543X     ISO Abbreviation:  Cancer     Publication Date:  2007 Jan 
Date Detail:
Created Date:  2007-01-17     Completed Date:  2007-02-26     Revised Date:  2009-06-08    
Medline Journal Info:
Nlm Unique ID:  0374236     Medline TA:  Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  248-55     Citation Subset:  AIM; IM    
Affiliation:
Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Anemia / chemically induced
Antineoplastic Agents, Phytogenic / administration & dosage,  adverse effects,  therapeutic use
Blast Crisis / drug therapy
Diarrhea / chemically induced
Dose-Response Relationship, Drug
Drug Administration Schedule
Fatigue / chemically induced
Female
Harringtonines / administration & dosage,  adverse effects,  therapeutic use*
Humans
Injections, Intravenous
Injections, Subcutaneous
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
Male
Middle Aged
Nausea / chemically induced
Piperazines / therapeutic use
Protein Kinase Inhibitors / therapeutic use
Pyrimidines / therapeutic use
Treatment Failure
Treatment Outcome
Chemical
Reg. No./Substance:
0/Antineoplastic Agents, Phytogenic; 0/Harringtonines; 0/Piperazines; 0/Protein Kinase Inhibitors; 0/Pyrimidines; 152459-95-5/imatinib; 26833-87-4/homoharringtonine
Comments/Corrections
Erratum In:
Cancer. 2007 Jun 15;109(12):2625
Note: Dosage error in article text

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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