Imatinib Compared with Imatinib/Cytarabine for the First-Line Treatment of Early Philadelphia Chromosome–Positive Chronic Myeloid Leukemia: Results of a Randomized Clinical Trial of the Mexican Collaborative Leukemia Group

2008 ◽  
Vol 2 (2) ◽  
pp. 128-132 ◽  
Author(s):  
Rafael Hurtado-Monroy ◽  
Pablo Vargas-Viveros ◽  
Myrna Candelaria ◽  
Eduardo Cervera ◽  
Judith Cruz ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Chronic Myeloid Leukemia ◽  
Randomized Clinical Trial ◽  
Myeloid Leukemia ◽  
Philadelphia Chromosome ◽  
Line Treatment ◽  
First Line ◽  
Leukemia Group ◽  
First Line Treatment ◽  
Philadelphia Chromosome Positive

scholarly journals Bosutinib Versus Imatinib for Newly Diagnosed Chronic Myeloid Leukemia: Results From the Randomized BFORE Trial

2018 ◽  
Vol 36 (3) ◽  
pp. 231-237 ◽  
Author(s):  
Jorge E. Cortes ◽  
Carlo Gambacorti-Passerini ◽  
Michael W. Deininger ◽  
Michael J. Mauro ◽  
Charles Chuah ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Hazard Ratio ◽  
Line Treatment ◽  
Newly Diagnosed ◽  
First Line ◽  
First Line Treatment ◽  
Philadelphia Chromosome Positive

Purpose Bosutinib is a potent dual SRC/ABL kinase inhibitor approved for adults with Philadelphia chromosome–positive chronic myeloid leukemia (CML) resistant and /or intolerant to prior therapy. We assessed the efficacy and safety of bosutinib versus imatinib for first-line treatment of chronic-phase CML. Methods In this ongoing, multinational, phase III study, 536 patients with newly diagnosed chronic-phase CML were randomly assigned 1:1 to receive 400 mg of bosutinib once daily (n = 268) or imatinib (n = 268). Per protocol, efficacy was assessed in patients who were Philadelphia chromosome–positive with typical (e13a2/e14a2) transcripts (bosutinib, n = 246; imatinib, n = 241). Patients with Philadelphia chromosome–negative–/ BCR-ABL1–positive status and those with unknown Philadelphia chromosome status and/or atypical BCR-ABL1 transcript type were excluded from this population. Results The major molecular response (MMR) rate at 12 months (primary end point) was significantly higher with bosutinib versus imatinib (47.2% v 36.9%, respectively; P = .02), as was complete cytogenetic response (CCyR) rate by 12 months (77.2% v 66.4%, respectively; P = .0075). Cumulative incidence was favorable with bosutinib (MMR: hazard ratio, 1.34; P = .0173; CCyR: hazard ratio, 1.38; P < .001), with earlier response times. Four patients (1.6%) receiving bosutinib and six patients (2.5%) receiving imatinib experienced disease progression to accelerated/blast phase. Among treated patients, 22.0% of patients receiving bosutinib and 26.8% of patients receiving imatinib discontinued treatment, most commonly for drug-related toxicity (12.7% and 8.7%, respectively). Grade ≥ 3 diarrhea (7.8% v 0.8%) and increased ALT (19.0% v 1.5%) and AST (9.7% v 1.9%) levels were more common with bosutinib. Cardiac and vascular toxicities were uncommon. Conclusion Patients who received bosutinib had significantly higher rates of MMR and CCyR and achieved responses faster than those who received imatinib. Consistent with the known safety profile, GI events and transaminase elevations were more common with bosutinib. Results indicate bosutinib may be an effective first-line treatment for chronic-phase CML.

A REVIEW ON THE ROLE OF TYROSINE KINASE INHIBITORS AVAILABLE FOR THE MANAGEMENT OF CHRONIC MYELOID LEUKEMIA

2020 ◽  
Vol 7 (2) ◽  
pp. 205-211
Author(s):  
Kaynat Fatima ◽  
Syed Tasleem Raza ◽  
Ale Eba ◽  
Sanchita Srivastava ◽  
Farzana Mahdi
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Protein Kinases ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

The function of protein kinases is to transfer a γ-phosphate group from ATP to serine, threonine, or tyrosine residues. Many of these kinases are linked to the initiation and development of human cancer. The recent development of small molecule kinase inhibitors for the treatment of different types of cancer in clinical therapy has proven successful. Significantly, after the G-protein-coupled receptors, protein kinases are the second most active category of drug targets. Imatinib mesylate was the first tyrosine kinase inhibitor (TKI), approved for chronic myeloid leukemia (CML) treatment. Imatinib induces appropriate responses in ~60% of patients; with ~20% discontinuing therapy due to sensitivity, and ~20% developing drug resistance. The introduction of newer TKIs such as, nilotinib, dasatinib, bosutinib, and ponatinib has provided patients with multiple options. Such agents are more active, have specific profiles of side effects and are more likely to reach the necessary milestones. First-line treatment decisions must be focused on CML risk, patient preferences and comorbidities. Given the excellent result, half of the patients eventually fail to seek first-line treatment (due to discomfort or resistance), with many of them needing a third or even further therapy lines. In the present review, we will address the role of tyrosine kinase inhibitors in therapy for chronic myeloid leukemia.

Is EUTOS Score Predictive Of Outcome In Patients With Early Chronic Phase Chronic Myeloid Leukemia Treated With Imatinib? Preliminary Data From The National Protocol Of The Chilean Cooperative Group Panda

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5196-5196 ◽  
Author(s):  
Javier Zelada ◽  
Marisa Pia Aida Capurro ◽  
Bernardita Rojas ◽  
Lilian M Pilleux ◽  
Augusto Aspillaga ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Predictive Value ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Cooperative Group ◽  
Line Treatment ◽  
First Line ◽  
Eutos Score ◽  
First Line Treatment

Abstract Background Before the Tirosine Kinase Inhibitors (TKI) era, the SOKAL and HASFORD scores have been used to predict outcome in chronic myeloid leukemia (CML) patients. The recently reported European Treatment and Outcome Study (EUTOS) score is a simple formula created to identify patients with significantly lower probabilities of responding to therapy and survival. The MD Anderson group didn´t validate this score. Aims To validate the EUTOS score in our population treated in the public health hospitals in Chile with a single protocol of the cooperative group PANDA. Methods Patients were selected from the data base of the CML 2007 PANDA protocol. All patients were adults (>15 years old) in early chronic phase and received first-line treatment with imatinib-based regimes and had a minimal follow up of twelve months. Event was defined as not reaching complete cytogenetic response in the first year of treatment, death from any cause at any time, loss of complete hematologic response, loss of major cytogenetic response, or progression to accelerated or blast phase. Overall survival (OS) was defined as death of any cause at any time. Event free survival (EFS) was defined as time from diagnosis to any event. Results A total of 78 patients were selected from the 330 patients of the data base. The rest had incomplete data. The median age was 48 (range 16 to 79 years old), 47 men and 31 women. Patients with low EUTOS score were 49 (63%) and 29 (37%) were high. The sensitivity of EUTOS was 46% , the specificity was 71% and the negative predictive value was 68%. There was no significative difference in EFS and OS in both EUTOS groups. Conclusions EUTOS score was not predictive of outcome in our patient population. Nevertheless it showed a good negative predictive value meaning that it can only identify low risk patients. This could be used in developing countries to select patients that could use lower cost TKI in first line treatment. Disclosures: No relevant conflicts of interest to declare.

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