Activity and tolerance of bosutinib in patients with AP and BP CML and Ph+ ALL

Gambacorti‐Passerini, Carlo; Kantarjian, Hagop; Baccarani, Michele; Porkka, Kimmo; Туркина, А Г; Zaritskey, Andrey; Agarwal, Shikha; Hewes, Becker; Khoury, H. Jean

doi:10.1200/jco.2008.26.15_suppl.7049

Cited by 14 publications

(10 citation statements)

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“…Study of a restricted cohort of pancreatic cancer, NSCLC, and colorectal cancer patients is ongoing [86]. Phase I/II studies in CML and Ph ϩ ALL patients who failed imatinib showed similar AEs as well as some mild dermatologic symptoms and variable hematologic toxicity [87,88] (Table 1). Although the body of clinical data supporting bosutinib has also been primarily applied to hematological malignancies, there are phase II trials in progress to study its efficacy in solid malignancies as well.…”

Section: Bosutinibmentioning

confidence: 99%

Current Status of Src Inhibitors in Solid Tumor Malignancies

2011

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Summary. Src is believed to play an important role in cancer, and several agents targeting Src are in clinical development.Design. We reviewed Src structure and function and preclinical data supporting its role in the development of cancer via a PubMed search. We conducted an extensive review of Src inhibitors by searching abstracts from major oncology meeting databases in the last 3 years and by comprehensively reviewing ongoing clinical trials on ClinicalTrials.gov.Results. In this manuscript, we briefly review Src structure and function, mechanisms involving Src that lead to the development of cancer, and Src inhibitors and key preclinical data establishing a rationale for clinical application. We then focus on clinical data supporting their use in solid tumor malignancies, a newer arena than their more well-established hematologic applications. Particularly highlighted are clinical trials investigating new biomarkers as well as ongoing studies assessing Src inhibitor activity in biomarker-selected patient populations. We also review newer investigational Src-targeting agents.Conclusions. Src inhibitors have shown little activity in monotherapy trials in unselected solid tumor patient populations. Combination studies and biomarker-driven clinical trials are under way. The Oncologist 2011;16:566 -578

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Section: Bosutinibmentioning

confidence: 99%

Current Status of Src Inhibitors in Solid Tumor Malignancies

2011

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“…Activity in advanced stage CML and Ph ? ALL has also been demonstrated [90]. A phase III comparison of bosutinib and imatinib in newly diagnosed patients with CML is currently in recruitment.…”

Section: Third-line Tyrosine Kinase Inhibitorsmentioning

confidence: 99%

Extending the duration of response in chronic myelogenous leukemia: targeted therapy with sequential tyrosine kinase inhibitors

Martin

DiPersio

2009

Oncol Rev

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Tyrosine kinase inhibitors (TKIs) are the mainstay for treatment of chronic myelogenous leukemia (CML). Imatinib was the first TKI approved for use in CML, but resistance to this therapy has emerged as a significant issue, and second-line options are often necessary. Increased-dose imatinib may elicit responses in some patients, but clinical evidence suggests only a minority experience sustained benefit. The second-generation TKIs, dasatinib and nilotinib, have demonstrated efficacy in patients resistant or intolerant to imatinib. Changes in therapy, with the aim of inducing durable response, should occur promptly after imatinib failure is identified as all agents are more effective in chronic phase disease than in later stages. Selection of second-line agents should be driven by efficacy and safety: dasatinib may be more effective in patients with P-loop or F359C mutations; nilotinib may be more effective in those with F317L mutations.

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“…Bosutinib: Two studies in 1019 relapsed patients, including some patients with Ph+ all, examined the efficacy of bosutinib 72,85 . In both studies, bosutinib was given at an oral dose of 500 mg once daily.…”

Section: 23mentioning

confidence: 99%

“…Twenty-four observational studies (twenty prospective, four retrospective) have examined the efficacy of a tki for the treatment of relapsed patients with Ph+ all. Of those studies, fourteen gave imatinib [13][14][15][16]23,29,32,37,42,49,55,56,61,63,75 , five gave dasatinib 44,50,71,83,88 , two gave nilotinib 50,75 , two gave bosutinib 72,85 , and one gave ponatinib 86 . The tkis were given with or without chemotherapy.…”

Section: Recommendation Grades Amentioning

confidence: 99%

“…As discussed earlier, three of the studies included both de novo and relapsed patients who had been given a tki. In five of the eighteen, a tki was given during induction for only a limited duration 23,31,32,44,71 ; ten studies gave a tki indefinitely until progression or toxicity 11,[14][15][16]45,61,72,85,86,88 ; and one study gave imatinib from 24 weeks onwards (that is, indefinitely) 13 . In addition, one study gave imatinib only as maintenance 55 .…”

Section: 22mentioning

confidence: 99%

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Evidence-Based Guidelines for the Use of Tyrosine Kinase Inhibitors in Adults with Philadelphia Chromosome–Positive or Bcr-Abl–Positive Acute Lymphoblastic Leukemia: A Canadian Consensus

Couban¹,

Savoie²,

Mourad

et al. 2014

Current Oncology

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Adult Philadelphia chromosome–positive (Ph+) or BCR-ABL–positive (BCR-ABL+) acute lymphoblastic leukemia (ALL) is an acute leukemia previously associated with a high relapse rate, short disease-free survival, and poor overall survival. In adults, allogeneic hematopoietic cell transplant in first remission remains the only proven curative strategy for transplant-eligible patients. The introduction of tyrosine kinase inhibitors (TKIS) in the treatment of patients with Ph+ or BCR-ABL+ ALL has significantly improved the depth and duration of complete remission, allowing more patients to proceed to transplantation. Although tkis are now considered a standard of care in this setting, few randomized trials have examined the optimal use of TKIS in patients with Ph+ ALL. Questions of major importance remain, including the best way to administer these medications, the choice of tki to administer, and the schedule and the duration to use. We present the results of a systematic review of the literature with consensus recommendations based on the available evidence.

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Activity and tolerance of bosutinib in patients with AP and BP CML and Ph+ ALL

Cited by 14 publications

References 0 publications

Current Status of Src Inhibitors in Solid Tumor Malignancies

Current Status of Src Inhibitors in Solid Tumor Malignancies

Extending the duration of response in chronic myelogenous leukemia: targeted therapy with sequential tyrosine kinase inhibitors

Evidence-Based Guidelines for the Use of Tyrosine Kinase Inhibitors in Adults with Philadelphia Chromosome–Positive or Bcr-Abl–Positive Acute Lymphoblastic Leukemia: A Canadian Consensus

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