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1.
J Coll Physicians Surg Pak ; 32(11): 1501-1502, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36377026

RESUMO

Imatinib is a CYP3A4 inhibitor, while ado-trastuzumab is a CYP3A4 substrate. Imatinib can interact with ado-trastuzumab emtansine (T-DM1) and can increase T-DM1 concentrations, leading to T-DM1-related toxicity. There is no trial or case report in the literature on the concomitant use of Imatinib and T-DM1. Herein, we report a case in which T-DM1 was used effectively with imatinib in a patient with chronic myeloid leukaemia (CML) and metastatic Her-2-positive breast cancer. A 37-year female using imatinib for CML was diagnosed with breast cancer and a modified radical mastectomy was performed. Skin metastasis occurred within one year after adjuvant therapy was completed. Lung metastasis occurred after Trastuzumab + vinorelbine treatment and T-DM1 and imatinib were given to the patient. No side effects were observed except for grade 1 fatigue. This case report is the first to report the concomitant use of T-DM1 and imatinib in a patient of CML and metastatic breast cancer. Key Words: Imatinib, Ado-trastuzumab emtansine, Breast cancer, Chronic myeloid leukaemia.


Assuntos
Ado-Trastuzumab Emtansina , Neoplasias da Mama , Mesilato de Imatinib , Feminino , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Mesilato de Imatinib/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Mastectomia , Maitansina/efeitos adversos , Receptor ErbB-2 , Trastuzumab/uso terapêutico
3.
Medicina (Kaunas) ; 58(10)2022 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-36295654

RESUMO

Background and Objectives: The aim of this study is to investigate the characteristics of gastrointestinal bleeding events associated with BCR-ABL tyrosine kinase inhibitor (TKI) treatment, using the reporting odds ratio (ROR) of the adverse event reports submitted to the Japanese Adverse Drug Event Report database between 2004 and 2020, and to examine the number of reported TKI-related gastrointestinal bleeding cases according to sex and age, as well as the actual number of TKI prescriptions issued in Japan. Materials and Methods: The RORs and 95% confidence intervals (CIs) of gastrointestinal bleeding events related to TKIs were calculated using the data of the 595,121 included cases. Results: Significant gastrointestinal bleeding events were detected for dasatinib (crude ROR: 4.47, 95% CI: 3.77-5.28) and imatinib (crude ROR: 1.22, 95% CI: 1.01-1.46). In multiple logistic regression analyses, significant gastrointestinal bleeding events were detected for dasatinib (adjusted ROR: 8.02, 95% CI: 5.75-10.2), imatinib (adjusted ROR: 1.81, 95% CI: 1.2-2.72), age (≥60 years, adjusted ROR: 2.22, 95% CI: 2.1-2.36), reporting year (adjusted ROR: 1.04, 95% CI: 1.04-1.05), and male sex (adjusted ROR: 1.47, 95% CI: 1.37-1.57). Interaction analysis revealed that the association of gastrointestinal bleeding with dasatinib was affected by age (≥60 years) and sex (female), with the number and proportion of dasatinib-related gastrointestinal bleeding cases increasing among those aged ≥60 years. Conclusions: Specific TKIs and patient characteristics were associated with gastrointestinal bleeding. Our results aid the prompt identification and treatment of TKI-related gastrointestinal bleeding.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Masculino , Feminino , Humanos , Dasatinibe/efeitos adversos , Mesilato de Imatinib/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/induzido quimicamente , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Pirimidinas/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/epidemiologia
4.
J Med Case Rep ; 16(1): 383, 2022 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-36271412

RESUMO

BACKGROUND: Molecular-targeted agents used as a treatment for cancer can cause some rare and serious adverse events such as, delayed wound healing. Depending on the anticancer drug used, temporary withdrawal may be recommended before and after surgery to avoid complications. Once a surgical incision has healed and closed completely, wounds rarely open because of the initiation of molecular targeted therapy several months to years after surgery. Here, we aimed to describe a rare complication of pharyngocutaneous fistula in two patients that was thought to be caused by molecular targeted therapy. CASE PRESENTATION: Case 1 involved a 64-year-old asian man who developed a delayed pharyngocutaneous fistula 3 months after total laryngectomy for laryngeal cancer. Ramucirumab, a vascular endothelial growth factor receptor inhibitor used for recurrent gastric cancer, was speculated to be involved. Case 2 involved a 71-year-old japanese man who developed a delayed pharyngocutaneous fistula 2 years and 1 month after total pharyngeal laryngectomy for pharyngeal cancer. It was speculated that imatinib, a platelet-derived growth factor receptor alpha inhibitor used for chronic myeloid leukemia, was involved. CONCLUSIONS: Although the incidence of late drug-induced anastomotic leakage is very low, when it occurs, it makes oral intake impossible for an extended period and interferes with the appropriate cancer treatment. In this report, we demonstrate the details of these two patients with such a rare complication, which may help accumulate essential data on this topic.


Assuntos
Fístula Cutânea , Neoplasias Laríngeas , Doenças Faríngeas , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Terapia de Alvo Molecular , Mesilato de Imatinib/efeitos adversos , Fator A de Crescimento do Endotélio Vascular , Fístula Cutânea/induzido quimicamente , Fístula Cutânea/cirurgia , Doenças Faríngeas/induzido quimicamente , Doenças Faríngeas/cirurgia , Laringectomia/efeitos adversos , Neoplasias Laríngeas/tratamento farmacológico , Neoplasias Laríngeas/cirurgia , Receptores do Fator de Crescimento Derivado de Plaquetas , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos
5.
Pharmacol Res Perspect ; 10(5): e01005, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36106342

RESUMO

Tyrosine kinase inhibitors (TKI) have revolutionized the treatment of chronic myeloid leukemia (CML), but patients still experience treatment-limiting toxicities or therapeutic failure. To investigate the real-world use and outcomes of imatinib in patients with CML in Australia, a retrospective cohort study of patients with CML commencing imatinib (2001-2018) was conducted across two sites. Prescribing patterns, tolerability outcomes, and survival and molecular response were evaluated. 86 patients received 89 imatinib treatments. Dose modifications were frequently observed (12-month rate of 58%). At last follow-up, 62 patients (5-year rate of 55%) had permanently discontinued imatinib treatment, of which 44 switched to another TKI (5-year rate of 46%). Within 3 months of starting imatinib, 43% (95% CI, 32%-53%) of patients experienced imatinib-related grade ≥3 adverse drug reactions (ADRs). Higher comorbidity score, lower body weight, higher imatinib starting dose, and Middle Eastern or North African ancestry were associated with a higher risk of grade ≥3 ADR occurrence on multivariable analysis (MVA). Estimated overall survival and event-free survival rates at 3 years were 97% (95% CI, 92%-100%) and 81% (95% CI, 72%-92%), respectively. Cumulative incidence of major molecular response (MMR) at 3 years was 63% (95% CI, 50%-73%). On MVA, imatinib starting dose, ELTS score, BCR-ABL1 transcript type, pre-existing pulmonary disease, and potential drug-drug interactions were predictive of MMR. In conclusion, imatinib induced deep molecular responses that translated to good survival outcomes in a real-world setting, but was associated with a higher incidence of ADRs, dose modifications and treatment discontinuations than in clinical trials.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Austrália/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológico , Humanos , Mesilato de Imatinib/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/induzido quimicamente , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Estudos Retrospectivos
6.
Lancet Haematol ; 9(11): e854-e861, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36174582

RESUMO

Several research and market developments in the past 5 years could influence front-line and subsequent-line strategies in chronic myeloid leukaemia. These developments include the increased availability of effective and safe generic imatinib at affordable prices, studies showing that doses of tyrosine kinase inhibitors (TKIs) lower than the approved dose are effective and less toxic, studies showing that dose-adjusted ponatinib therapy at a reduced dose is effective and substantially safer than approved doses, and the approval of asciminib as third-line therapy in 2021. With the availability of an affordable generic imatinib, all patients with chronic myeloid leukaemia globally should be able to access a lifetime supply. The availability of reduced-dose schedules of generic second-generation TKIs, which are less toxic and produce faster deep molecular response than imatinib, might make them more appealing to use as front-line therapy. In the subsequent-line setting, the role of different TKIs as second, third, and later lines of therapy depends on the evolving front-line use. Dose-adjusted ponatinib schedules have shown better efficacy and safety with long-term follow-up. Ponatinib is the favoured therapy for patients with second-generation-TKI resistance or chronic myeloid leukaemia with 944C→T (Thr315Ile)-mutated BCR-ABL1. Studies of asciminib are needed in larger numbers of patients and with longer follow-up than has been done previously to better assess its comparative efficacy, safety, and survival data (vs ponatinib). The role of third-generation TKIs as second-line therapy following front-line resistance to second-generation TKIs needs to be evaluated. New and mature data with TKI therapy in chronic myeloid leukaemia are producing observations that encourage continuous discussion of the optimal treatment recommendations and frameworks in chronic myeloid leukaemia.


Assuntos
Antineoplásicos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Humanos , Mesilato de Imatinib/efeitos adversos , Proteínas de Fusão bcr-abl/genética , Inibidores de Proteínas Quinases/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Medicamentos Genéricos/uso terapêutico , Marketing , Antineoplásicos/efeitos adversos
7.
Int J Hematol ; 116(6): 863-870, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35932399

RESUMO

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myeloid leukemia (CML). However, TKI-related chronic renal toxicity has been reported, particularly in patients with hypertension. We assessed whether incidental use of specific types of antihypertensive drugs, including renin-aldosterone-angiotensin system inhibitors (RAASis), affects the change in estimated glomerular filtration rate (eGFR) during TKI treatment. We retrospectively analyzed all eGFR measurements during TKI treatment for 142 CML patients at Kyushu University Hospital, estimating the rate of eGFR change using a mixed-effects model. Overall, a significant interaction was found between the type of antihypertensive medication used and the yearly change in eGFR (P < 0.01), with RAASi users exhibiting the most rapid decrease in eGFR (- 5.5%/year). The analysis by TKI used showed that the interaction was significant only in imatinib and bosutinib users (P < 0.01 and P = 0.04, respectively). The yearly rate of eGFR decrease was the most notable in RAASi users, at - 5.7 (- 6.6, - 4.9) and - 10.1 (- 12.3, - 7.9) for imatinib and bosutinib users, respectively. Our findings indicate that eGFR should be carefully monitored in patients taking these TKIs.


Assuntos
Anti-Hipertensivos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Humanos , Mesilato de Imatinib/efeitos adversos , Taxa de Filtração Glomerular , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Aldosterona/farmacologia , Aldosterona/uso terapêutico , Renina/farmacologia , Renina/uso terapêutico , Estudos Retrospectivos , Inibidores de Proteínas Quinases/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Inibidores Enzimáticos/uso terapêutico , Angiotensinas/farmacologia , Angiotensinas/uso terapêutico
8.
J Clin Oncol ; 40(34): 3918-3928, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-35947817

RESUMO

PURPOSE: Sunitinib, a multitargeted tyrosine kinase inhibitor (TKI), is approved for advanced gastrointestinal stromal tumor (GIST) after imatinib failure. Ripretinib is a switch-control TKI approved for advanced GIST after prior treatment with three or more TKIs, including imatinib. We compared efficacy and safety of ripretinib versus sunitinib in patients with advanced GIST who were previously treated with imatinib (INTRIGUE, ClinicalTrials.gov identifier: NCT03673501). PATIENTS AND METHODS: Random assignment was 1:1 to once-daily ripretinib 150 mg or once-daily sunitinib 50 mg (4 weeks on/2 weeks off) and stratified by KIT/platelet-derived growth factor α mutation and imatinib intolerance. The primary end point was progression-free survival (PFS) by independent radiologic review using modified Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points included objective response rate by independent radiologic review, safety, and patient-reported outcome measures. RESULTS: Overall, 453 patients were randomly assigned to ripretinib (intention-to-treat [ITT], n = 226; KIT exon 11 ITT, n = 163) or sunitinib (ITT, n = 227; KIT exon 11 ITT, n = 164). Median PFS for ripretinib and sunitinib (KIT exon 11 ITT) was 8.3 and 7.0 months, respectively (hazard ratio, 0.88; 95% CI, 0.66 to 1.16; P = .36); median PFS (ITT) was 8.0 and 8.3 months, respectively (hazard ratio, 1.05; 95% CI, 0.82 to 1.33; nominal P = .72). Neither was statistically significant. Objective response rate was higher for ripretinib versus sunitinib in the KIT exon 11 ITT population (23.9% v 14.6%, nominal P = .03). Ripretinib was associated with a more favorable safety profile, fewer grade 3/4 treatment-emergent adverse events (41.3% v 65.6%, nominal P < .0001), and better scores on patient-reported outcome measures of tolerability. CONCLUSION: Ripretinib was not superior to sunitinib in terms of PFS. However, meaningful clinical activity, fewer grade 3/4 treatment-emergent adverse events, and improved tolerability were observed with ripretinib.


Assuntos
Antineoplásicos , Tumores do Estroma Gastrointestinal , Humanos , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/patologia , Mesilato de Imatinib/efeitos adversos , Sunitinibe/uso terapêutico , Pirróis/efeitos adversos , Indóis/efeitos adversos , Resistencia a Medicamentos Antineoplásicos , Inibidores de Proteínas Quinases/efeitos adversos , Mutação , Antineoplásicos/efeitos adversos , Proteínas Proto-Oncogênicas c-kit/genética
10.
Contact Dermatitis ; 87(5): 447-450, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35837878

RESUMO

BACKGROUND: Imatinib mesylate is a first-generation tyrosine kinase inhibitor. Piperamido Nitrotoluene, also known as F5, is an intermediate used in the manufacturing of imatinib. We present a case series of allergic contact dermatitis to F5 in pharmaceutical workers. METHODS: Four male pharmaceutical workers were referred between 2007 and 2021 with new dermatitis predominantly affecting the periorbital region. All were involved in the production of imatinib and particularly exposed to F5. Following medical history and examination, they underwent patch testing to standard series and F5 diluted in white soft paraffin (WSP). RESULTS: All patients tested positive confirming a diagnosis of contact allergy to F5. The first case tested positive to F5 diluted to 1% in WSP, the second to F5 diluted to 10% in WSP and the third and fourth to F5 diluted to 1% and 10% in WSP. In all four cases, dermatitis resolved when they were removed from exposure to F5. CONCLUSIONS: To the best of our knowledge, these are the first cases of allergic contact dermatitis to F5 confirmed by patch testing in the literature. In February 2016, a generic formulation of imatinib entered the market. Globalized production of imatinib may result in further cases presenting to dermatology departments worldwide.


Assuntos
Dermatite Alérgica de Contato , Dermatite Ocupacional , Indústria Farmacêutica , Exposição Ocupacional , Alérgenos , Dermatite Alérgica de Contato/diagnóstico , Dermatite Alérgica de Contato/etiologia , Dermatite Ocupacional/diagnóstico , Dermatite Ocupacional/etiologia , Humanos , Mesilato de Imatinib/efeitos adversos , Masculino , Exposição Ocupacional/efeitos adversos , Parafina , Testes do Emplastro , Preparações Farmacêuticas , Inibidores de Proteínas Quinases , Tolueno
11.
Clin Pharmacol Drug Dev ; 11(10): 1233-1240, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35900031

RESUMO

Nilotinib, a second-generation tyrosine kinase inhibitor (TKI), has been approved in the United States and Europe as a treatment for patients with newly diagnosed chronic myeloid leukemia (CML)-chronic phase (CP) and patients with CML-CP or chronic myeloid leukemia-accelerated phase (CML-AP) who are resistant or intolerant to imatinib (a first-generation TKI). This study compared the bioequivalence and safety of the test nilotinib capsule and reference nilotinib capsule (Tasigna, Novartis) in healthy Chinese volunteers under fasting conditions for marketing authorization in China. The results of the study are reported for the first time. This was a single-dose, randomized, open-label, two-period, and cross-over study. Thirty healthy volunteers were randomly assigned to receive a single dose of a 200-mg test or reference capsule under fasting conditions in each period with a 10-day washout. Plasma samples were analyzed with liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were calculated with WinNonlin software. The geometric mean ratio and the corresponding 90% confidence intervals of Cmax , AUC0-t , and AUC0-∞ for nilotinib between the two fixed-dose combination formulations were within the bioequivalence acceptance range of 80%-125%, therefore the generic and branded formulations were bioequivalent in healthy Chinese volunteers.


Assuntos
Medicamentos Genéricos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Área Sob a Curva , China , Estudos Cross-Over , Medicamentos Genéricos/efeitos adversos , Medicamentos Genéricos/farmacocinética , Voluntários Saudáveis , Humanos , Mesilato de Imatinib/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Pirimidinas , Equivalência Terapêutica
12.
Drug Des Devel Ther ; 16: 1595-1604, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35669281

RESUMO

Background: Imatinib is used to treat chronic myelogenous leukemia (CML). Variations in imatinib pharmacokinetics have been linked to genetic variations. That has an impact on imatinib response and adverse effects. Therefore, the aim of the study was to study bone pain as an adverse effect that occurs with imatinib and to investigate the risk factors for bone pain. Methods: The relationship between the peak and trough plasma concentrations of imatinib with bone pain as one of the most frequently occurring adverse effects was examined. Multiple linear regression analysis and binary logistic regression analysis were used to measure the impact of various patients' characteristics on both peak and trough imatinib concentrations and the risk of the occurrence of imatinib-induced bone pain. Results: As a side effect of imatinib, approximately 15% of patients with CML who were taking it experienced bone pain. This side effect was linked to the imatinib peak and trough plasma levels. Imatinib trough concentration was also linked to gender and the gene SLCO1B3-334T > G (TT). There were significant associations between peak concentrations and gender as well as patient weight. Conclusion: Higher peak and trough plasma concentrations of imatinib are linked with the risk of the occurrence of bone pain as a side effect of imatinib. Monitoring plasma concentrations of imatinib is useful to predict the bone pain of imatinib and to support quality of life in patients with CML.


Assuntos
Antineoplásicos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Antineoplásicos/efeitos adversos , Humanos , Mesilato de Imatinib/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Dor/tratamento farmacológico , Qualidade de Vida
13.
Int J Cancer ; 151(10): 1770-1777, 2022 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-35678337

RESUMO

Three years of adjuvant imatinib is the current standard for patients with high-risk gastrointestinal stromal tumors (GIST). We aimed to investigate the safety and efficacy profiles of 3-year imatinib, focusing on the prognostic value of various factors. In this registry-based study, 222 patients with high-risk GIST who underwent surgical resection followed by 3 years of adjuvant imatinib between 2010 and 2018 were included. The imatinib dose was reduced in 39 (17.6%), and 13 (5.9%) discontinued imatinib due to toxicity. With a median follow-up duration of 65.7 months, 5-year recurrence-free survival (RFS) and overall survival (OS) were 73.2% and 93.9%, respectively. Tumor rupture, tumor size of >10 cm, mitotic index of >10/50 high power fields (HPF) were independent factors for short RFS. Patient subgroups stratified by the risk factors showed distinct RFS (P < .001): patients without the above risk factors or those with only a tumor size of >10 cm showed favorable RFS (5-year RFS 83.8% and 92.3%, respectively), whereas those with tumor rupture or those with tumor size of >10 cm and mitotic index of >10/50 HPF showed prominently poor RFS (5-year RFS of 54.8% and 47.9%, respectively). Three years of adjuvant imatinib treatment was generally tolerable and effective, which were consistent with the clinical outcomes of previous reports. The presence of tumor rupture, large tumor and high mitotic count was independently associated with poor RFS. Based on these risk factors, different management strategies, such as different durations of adjuvant imatinib, deserve further investigation.


Assuntos
Antineoplásicos , Tumores do Estroma Gastrointestinal , Adjuvantes Imunológicos/uso terapêutico , Antineoplásicos/efeitos adversos , Benzamidas/uso terapêutico , Quimioterapia Adjuvante , Tumores do Estroma Gastrointestinal/patologia , Humanos , Mesilato de Imatinib/efeitos adversos , Recidiva Local de Neoplasia/tratamento farmacológico , Piperazinas/efeitos adversos , Prognóstico , Pirimidinas/uso terapêutico
14.
Leukemia ; 36(7): 1825-1833, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35643868

RESUMO

This analysis from the multicenter, open-label, phase 3 BFORE trial reports efficacy and safety of bosutinib in patients with newly diagnosed chronic phase (CP) chronic myeloid leukemia (CML) after five years' follow-up. Patients were randomized to 400-mg once-daily bosutinib (n = 268) or imatinib (n = 268; three untreated). At study completion, 59.7% of bosutinib- and 58.1% of imatinib-treated patients remained on study treatment. Median duration of treatment and time on study was 55 months in both groups. Cumulative major molecular response (MMR) rate by 5 years was higher with bosutinib versus imatinib (73.9% vs. 64.6%; odds ratio, 1.57 [95% CI, 1.08-2.28]), as were cumulative MR4 (58.2% vs. 48.1%; 1.50 [1.07-2.12]) and MR4.5 (47.4% vs. 36.6%; 1.57 [1.11-2.22]) rates. Superior MR with bosutinib versus imatinib was consistent across Sokal risk groups, with greatest benefit seen in patients with high risk. Treatment-emergent adverse events (TEAEs) were consistent with 12-month data. After 5 years of follow-up there was an increase in the incidence of cardiac, effusion, renal, and vascular TEAEs in bosutinib- and imatinib-treated patients, but overall, no new safety signals were identified. These final results support 400-mg once-daily bosutinib as standard-of-care in patients with newly diagnosed CP CML.This trial was registered at www.clinicaltrials.gov as #NCT02130557.


Assuntos
Antineoplásicos , Leucemia Mieloide de Fase Crônica , Quinolinas , Compostos de Anilina/efeitos adversos , Antineoplásicos/efeitos adversos , Humanos , Mesilato de Imatinib/efeitos adversos , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Nitrilas , Inibidores de Proteínas Quinases/efeitos adversos , Quinolinas/efeitos adversos , Resultado do Tratamento
15.
Leuk Lymphoma ; 63(9): 2213-2223, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35491715

RESUMO

We report on long-term outcomes of 267 patients (pts) with chronic myeloid leukemia (CML) treated with imatinib administered as initial therapy. The median follow-up time was 11.4 years. 38 (14.2%) pts attempted to discontinue imatinib therapy after achieving sustained deep molecular response (≥MR4), 15 of them achieved treatment-free remission (TFR). 144 pts (53.9%) have been switched to other TKI during the follow-up period. The estimated OS for 267 pts for 10, 15 and 18 years was 98.8%, 75.6% and 52.1%. According to prognostic scores (Sokal, Euro, ELTS), OS and PFS were significantly better in low-risk pts than in high-risk pts. According to ELTS, low-risk pts have a better chance of achieving MR4 than both intermediate (p = 0.03) and high-risk (p = 0.04) groups. It suggests that a specific ELTS-adapted treatment could help to optimize treatment results. In the study population, imatinib has demonstrated sustained efficacy and an acceptable rate of late toxic effects.


Assuntos
Antineoplásicos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Antineoplásicos/efeitos adversos , Progressão da Doença , Humanos , Mesilato de Imatinib/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Resultado do Tratamento
16.
J Cancer Res Ther ; 18(1): 253-256, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35381793

RESUMO

Imatinib is a tyrosine kinase inhibitor that selectively inhibits several protein tyrosine kinases which is central to the pathogenesis of human cancer. It forms the first-line treatment for chronic myeloid leukemia (CML) and gastrointestinal stromal tumors. Usually, the drug is well-tolerated with relatively few side effects. Adverse effects most commonly associated with imatinib include mild-to-moderate edema, nausea and vomiting, diarrhea, muscle cramps, and cutaneous reactions. Other side effects such as the elevation of hepatic transaminase and myelosuppression occur less frequently and resolve with interruption of imatinib therapy. Skin rash is one of the most common adverse effects of imatinib incidence of which range from 7% to 88.9%. Exfoliative dermatitis, i.e., erythroderma has been very rarely reported with this drug. We here report a rare case of erythroderma in a patient with CML on imatinib 400 mg/day therapy within 3 months of starting the treatment.


Assuntos
Antineoplásicos , Dermatite Esfoliativa , Tumores do Estroma Gastrointestinal , Leucemia Mielogênica Crônica BCR-ABL Positiva , Antineoplásicos/efeitos adversos , Dermatite Esfoliativa/induzido quimicamente , Dermatite Esfoliativa/diagnóstico , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Humanos , Mesilato de Imatinib/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico
17.
Front Endocrinol (Lausanne) ; 13: 794512, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35399933

RESUMO

Tyrosine kinase inhibitors (TKIs) are nowadays a valuable treatment of desmoid tumors, a rare mesenchymal neoplasm. Although many side effects of imatinib and pazopanib, commonly or rarely occurring, have been described, reactional lymphadenopathy has not yet been reported. In this publication, we report two cases of patients with desmoid tumors, treated with pazopanib and imatinib, who developed reactional lymphadenopathy. As this side effect is presented as a newly formed mass, it can result in new diagnostic questions and added imaging tests and can even lead to discontinuation of the treatment. This report may help the clinicians facing similar problems adopt a "watch and wait" approach.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Fibromatose Agressiva , Linfadenopatia , Fibromatose Agressiva/tratamento farmacológico , Fibromatose Agressiva/patologia , Humanos , Mesilato de Imatinib/efeitos adversos , Linfadenopatia/induzido quimicamente , Inibidores de Proteínas Quinases/efeitos adversos
18.
Ann Med ; 54(1): 1244-1254, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35486442

RESUMO

INTRODUCTION: Few studies have reported the outcomes of adolescents and young adults (AYAs) with chronic-phase chronic myeloid leukaemia (CML-CP) on tyrosine kinase inhibitors (TKIs). MATERIALS AND METHODS: We retrospectively analysed the clinical features, treatment response, and long-term outcomes of 42 AYA patients, in comparison to older patients. The initial therapies of AYA patients between 2001 and 2016 included imatinib (n = 24), dasatinib (n = 13) and nilotinib (n = 5). RESULTS: In AYA patients, the peripheral blood (PB) white blood cell count and percentage of blasts at the diagnosis were significantly higher, haemoglobin levels were lower and the spleen size was larger. The major molecular response (MMR), event-free survival (EFS) and overall survival (OS) rates were comparable. A sub-analysis comparing imatinib to second-generation TKIs as the initial therapy also showed that their prognosis was comparable. DISCUSSION: In conclusion, the tumour burden at the diagnosis of CML-CP is higher in AYA patients; however, their prognosis was not worse in comparison to older patients treated with TKIs. KEY MESSAGESFew studies have reported the outcomes of adolescents and young adults (AYAs) with chronic-phase chronic myeloid leukaemia (CML-CP) on tyrosine kinase inhibitors (TKIs). This study showed the tumour burden at the diagnosis of CML-CP is higher in AYA pa tients; however, their prognosis was not worse in comparison to older patients treated with TKIs. Understanding the biological and non-biological features of AYA patients with CML-CP on TKI therapy is essential for better management and to improve the outcomes.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Leucemia Mieloide de Fase Crônica , Adolescente , Humanos , Mesilato de Imatinib/efeitos adversos , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mieloide de Fase Crônica/diagnóstico , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Retrospectivos , Adulto Jovem
19.
Leuk Lymphoma ; 63(9): 2224-2232, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35475716

RESUMO

Despite a favorable effect of imatinib on glucose metabolism in animal models, human reports are inconsistent. We retrospectively studied the long-term effect of imatinib on fasting plasma glucose (FPG), glycated hemoglobin (HbA1C), LDL-cholesterol (LDL), and triglycerides (TGs) in a large HMO cohort of patients initiating therapy. In patients with diabetes (n = 118), significant reductions in HbA1c (0.53%, IQR 0.09, 1.19; p < .001) and FPG (10.2 mg/dL, IQR -3.5, 32.2; p < .001), independent of demographics and of glucose-lowering drugs utilization, were observed during the first year of imatinib treatment. Significant reductions in LDL (17.8 mg/dL, IQR -1.3, 34.0; p < .001) and TG (25.0 mg/dL, IQR -2.3, 58.3; p < .001), also independent of demographics and of statin utilization, were evident in the entire cohort (n = 611) during the first imatinib year. All reductions persisted during the second treatment year. To conclude, imatinib is associated with durable metabolic benefits, which may guide TKI choice in patients with cardiovascular co-morbidities.


Assuntos
Diabetes Mellitus Tipo 2 , Inibidores de Hidroximetilglutaril-CoA Redutases , Glicemia , LDL-Colesterol/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobina A Glicada/análise , Hemoglobina A Glicada/metabolismo , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Mesilato de Imatinib/efeitos adversos , Estudos Retrospectivos , Triglicerídeos/uso terapêutico
20.
Pediatr Blood Cancer ; 69(8): e29714, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35441424

RESUMO

Although skin complications are common adverse events from tyrosine kinase inhibitors (TKIs) for the treatment of chronic myeloid leukemia (CML), no reports have focused on skin and soft tissue infections (SSTIs) associated with TKI use. We herein present five episodes of SSTIs in three CML patients under dasatinib treatment. All patients were adolescents and had been receiving dasatinib for more than 4 years. In contrast, none of 41 adult CML patients experienced SSTIs in a retrospective analysis. Our findings suggest that long-term dasatinib treatment in adolescent patients may be associated with the increased risk of SSTIs.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Infecções dos Tecidos Moles , Adolescente , Adulto , Dasatinibe/efeitos adversos , Humanos , Mesilato de Imatinib/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Pirimidinas/efeitos adversos , Estudos Retrospectivos , Infecções dos Tecidos Moles/induzido quimicamente
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