scholarly journals Efficacy and safety of nilotinib as third-line therapy in an elderly patient with CML

2015 ◽  
Vol 6 (2S) ◽  
pp. 15-18
Author(s):  
Giovanni Caocci ◽  
Sandra Atzeni ◽  
Giorgio La Nasa
Keyword(s):  
Pleural Effusion ◽  
Tyrosine Kinase ◽  
Kinase Inhibitors ◽  
Day Treatment ◽  
Skin Toxicity ◽  
Drug Dose ◽  
Molecular Response ◽  
Line Therapy ◽  
Third Line Therapy ◽  
Third Line

This case report describes a 74 year old male patient with low Sokal risk chronic myeloid leukemia (CML). Treatment was started four years ago with imatinib, 400 mg/day. The patient achieved complete hematologic response but, after 3 months of treatment, developed grade 3 skin toxicity. Imatinib was stopped and the patient was started on dasatinib, achieving complete cytogenetic and molecular response. Two months later, physical examination revealed bilateral gynecomastia. After 2 years of treatment the patient presented with pleural effusion and the drug dose was reduced but, following relapse of CML, therapy was switched to nilotinib, 800 mg/day. Treatment with nilotinib is currently ongoing and is well tolerated by the patient who is again in complete molecular response, with no signs of pleural effusion. Considering the growing availability of new and more potent tyrosine kinase inhibitors (TKI) it is important for the clinician to be aware of the possible inhibitory effects of these molecules against other members of the tyrosine kinase family. Safety of TKI in frail and elderly patients with CML is a fundamental goal. The results achieved in our patient show that nilotinib is safe and effective even when used as third line therapy.

scholarly journals Dasatinib tyrosine kinase inhibitor as second and third line therapy in chronic myeloid leukemia: outcome of a Nepalese study

2018 ◽  
Vol 5 (1) ◽  
pp. 47-56
Author(s):  
Nora Ranjitkar Manandhar ◽  
Gyan Krishna Kayashta ◽  
Paras Kumar Acharya
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Molecular Response ◽  
Second Line ◽  
Line Therapy ◽  
Third Line Therapy ◽  
Third Line

Introductions: Dasatinib is indicated as a first line, second line and third line tyrosine kinase inhibitor (TKI) in chronic myeloid leukemia (CML). In our center it is used as a second line or third line therapy in BCR-ABL gene positive CML. Methods: It is a retrospective observational therapy done from June 2015 to May 2018. The purpose of the study is to see the response rates using the second line and third line dasatinib after failing or not tolerating imatinib alone or following a sequential therapy with imatinib and nilotinib. Results: A total of 31 (male 56.3%) patients were included in our study. In eighteen patients it was used as a second line TKI and in 13 a third line TKI. Complete Hematologic Response (CHR) was achieved in 93.55%. Best optimal responses were 46.66% and 61.53% in second and third line dasatinib respectively. Major Molecular Response (MMR) was achieved in 35.71% (26.66% and 46.14% in second line and third line dasatinib respectively). For both the groups, the overall survival was 92% and 94 % at 20 months and the event free survival was 70% at 10 months. Conclusions: Dasatinib is effective in achieving MMR and inducing survival benefit in the patients who failed imatinib alone and imatinib and nilotinib.

Comparasion Between Nilotinib and Dasatinib as Second-Line Therapy for Patients with Chronic Myeloid Leukemia: A Single Center Retrospective Study.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3440-3440
Author(s):  
Clarisse Lobo ◽  
Carla Boquimpani ◽  
Tania Silva Madeira ◽  
Patricia Wendling ◽  
Claudia Maximo ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Second Generation ◽  
Randomized Clinical Trials ◽  
Molecular Response ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Third Line Therapy ◽  
Third Line

Abstract Abstract 3440 Nilotinib and dasatinib are second-generation tyrosine kinase inhibitors (TKI) used in patients with chronic myeloid leukemia (CML) resistant or intolerant to imatinib. There are no randomized clinical trials comparing these drugs in this context. The aim of this study was to compare, retrospectively, the hematological, cytogenetic and molecular response in patients submitted to these second-generation TKI at Hemorio, a public brazilian institution. A total of 114 patients were analyzed, 63 received nilotinib and 51 dasatinib as second-line therapy (55.3% and 44.7%, respectively). The following variables were equally distributed between these two groups (nilotinib vs. dasatinib, respectively): male sex (54% vs. 60.8%, p=0.46), median age at diagnosis (46 vs. 45 years, p=0.76), median time in months using imatinib before the switch (45.2 vs. 44.1, p=0.96), resistance to imatinib (98.4% vs. 98%, p=0.88), presence of the mutation T315I (3.2% vs. 3.9%, p=0.09), patients in chronic phase before the switch (85.7% vs. 86.3%, p=0.93). Use of another second generation TKI, as a third-line therapy, was necessary in 30 out of the 114 patients analyzed (26.1%) because of lack of response. This modification was slightly more frequent in the group initially submitted to nilotinib (31.7% vs. 19.6%, p=0.21). Patients who used a third-line therapy were excluded from response and survival analyzes. Response rates after the second-generation TKI were similar between these two groups (nilotinib vs. dasatinib): complete hematological response until three months (77.8% vs. 87.3%, p=0.24), complete cytogenetic response until six months (21.6% vs. 22.2%, p=0.95) and 12 months (32.4% vs. 33.3%, p=0.94) and major molecular response reached before 12 months (32.7% vs. 21.6%, p=0.25). Two-year overall survival (OS) and progression free-survival (PFS) were similar between these two groups (nilotinib vs. dasatinib, respectively): 92.2% vs. 87.8% (p=0.38) for OS and 87.8% vs. 83.7% (p=0.14) for PFS. Although not statistically significant, two-year OS was inferior in the group of patients who needed a third-line therapy (70.5% vs. 95.6%, p=0.70). Our results suggest that the response and survival rates are similar between nilotinib and dasatinib as second-line therapy for patients with imatinib resistant or intolerant CML. Also, they suggest an inferior prognosis for patients who need a third-line therapy. In this way, the choice between these two TKI for second-line therapy should be guided by the clinical characteristics and the mutation status of the patient. Disclosures: Lobo: NOVARTIS: Research Funding.

Treatment Results With Dasatinib Or Nilotinib In Third Line Therapy Of Chronic Myeloid Leukemia After Failure Of Two Tyrosine Kinase Inhibitors

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5189-5189
Author(s):  
Beatriz F Ribeiro ◽  
Eliana C M Miranda ◽  
Marcia T Delamain ◽  
Gislaine Borba Oliveira ◽  
Maria Helena Almeida ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Cytogenetic Response ◽  
Molecular Responses ◽  
The Third ◽  
Line Therapy ◽  
Third Line Therapy ◽  
Third Line ◽  
Tki Discontinuation

Abstract Chronic myeloid leukemia (CML) patients with imatinib failure are usually treated with second generation tyrosine kinase inhibitors (TKI). In case of dasatinib or nilotinib intolerance or resistance patients with HLA matched donor are submitted to allogeneic hematopoietic stem cell transplantation (HSCT) or switch treatment to a different TKI. Aims to evaluate complete hematological response (CHR), cytogenetic and molecular responses, overall, progression free and event free survival (OS, FPS and EFS) in CML patients in third line therapy that previously used 2 TKI. BCR-ABL mutations was also evaluated in this population Patients and methods between July 2008 and August 2012 26 CML patients were evaluated: 10 patients (pts) treated with dasatinib (38,5%) and 16 with nilotinib (61,5%) in third line therapy. OS, PFS and EFS were calculated with Kaplan-Meier method and Log-Rank was used for comparison, from the date of the third TKI start. The events for PFS were progression to accelerated phase (AP) or blast crisis (BC) and death. For EFS, were considered loss of CHR, loss of complete cytogenetic response (CCR), TKI discontinuation for failure or intolerance, progression or death. Patients were censored in HSCT date or TKI discontinuation for cytogenetic and molecular responses evaluation, but not for OS. Mutational analysis was done with Sanger sequencing. Results 13 male (50%) and 13 female patients with median age 54 years (22-75) and median follow-up of 32 months were analyzed (1-59). Previous response to imatinib: only one patient has achieved CCR. Status before third TKI start: 19 (73%) less than partial cytogenetic response (PCyR); 2 (7,7%) PCyR; 4 (15,5%) CCR;and 1 (3,8%) clonal evolution. 8/18 (42%) patients presented the following mutations: F317L (2), E255V (1), Y253H (1), M351T (1), M244V (1) e F359V (2). The median time of the third TKI treatment was 171 days (15-1140). Responses to third line TKI: CHR 17/19 (89%) in CP; 3/3 AF; 0/4 BC; CCR: 3/19 in CP (2 pts at 3 months and one in the 12º month); 1/3 AP; 0/4 BC; MMR: 4/19 in CP; 1/3 AP; 0/4 in BC. Nine lost CHR (45%) (8 in CP and one in AP). At 3 months, 1/21 pts (4.5%) achieved MMR; 2/13 (15%) at 6 months, while at 12 months 1/11 (9%) had MMR. At 3 months 11/21 had a BCR-ABL/ABL(IS) >10% and at 6 months 10/13 >1%. Three patients progressed to advanced phases (11,5%) ; 6 (23%) died (4 due to LMC, 1 acute myocardial infarction and 1 from graft vs host disease after HSCT; one lost follow-up. Third line treatment was discontinued in 12 (46%) pts: 6 for resistance, 2 death; 2 intolerance and resistance; 1 intolerance and one loss of follow-up. OS, PFS and EFS were 69%, 68% e 30% respectively(figure 1). OS was inferior in AP and BC in comparison with CP (0% vs 50% vs 90% - p< 0,0001)(figure 2). In summary responses may be obtained with dasatinib or nilotinib after 2 TKI failure, but they are not durable in advanced phases. Besides the results, that is an alternative for disease stabilization until the identification of a suitable donor or for patients with no performance status for HSCT. Disclosures: No relevant conflicts of interest to declare.

Sequential TKI treatments for iodine-refractory differentiated thyroid carcinomas.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6092-6092
Author(s):  
Christelle de la Fouchardiere ◽  
Marie-Helene Massicotte ◽  
Isabelle Borget ◽  
Maryse Brassard ◽  
Mederic Claude-Desroches ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Specific Treatment ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
Off Label ◽  
Line Therapy ◽  
Number Of Patients ◽  
Third Line Therapy ◽  
Third Line

6092 Background: Tyrosine kinase inhibitors (TKI) are currently used to treat patients with advanced iodine-refractory differentiated thyroid cancers (DTC) but none has been approved by the FDA or the EMA until now. Sometimes, patients are treated with off-label TKI when a clinical trial is not available or in second- and third-line therapy. Methods: We hereby report the efficacy of “off-label” sorafenib and sunitinib treatments as first-, second- and third-line therapy in metastatic DTC patients from the French TUTHYREF (TUmeurs THYroïdiennes REFractaires) network. Primary endpoints were progression free survival (PFS) and tumor response according to sequential TKI treatment. Secondary endpoint was organ-specific metastatic site analysis. Results: 45 patients with advanced iodine-refractory DTC treated with off-label TKI were included in this study (26 men, mean age: 62 years). 22 had papillary, 10 had follicular and 13 had poorly DTC. 24/45 patients were treated with two and 3/45 with three lines of TKIs. Sorafenib was the most frequently used (57%) followed by sunitinib (21.5%) and vandetanib (21.5%). Partial response (PR) rate was of 29% in the 21 patients who received first-line sorafenib therapy whereas PR was observed in 57% of the 7 first-line sunitinib patients. There was no PR with second- (n=24) and third-line (n=3) treatments. However, median progression free survival (PFS) was similar in second- as compared to first-line sorafenib or sunitinib treatment (6.7 vs. 7.6 months, HR 0.85 (95CI 0.45-1.61) p=0.6). Liver metastases were the most responsive to treatment (n=7; mean of -30%), followed by lung (n=57; mean of -19%) and lymph node (n=43; mean of -13%) metastases. Bone (n=14) and pleural (n=9) lesions were the most refractory to treatment (mean of -1% and -5%, respectively). Conclusions: Due to the small number of patients, we could not recommend a specific treatment sequence (sorafenib then sunitinib) over another (sunitinib then sorafenib). But TKI therapy appears to be beneficial in refractory DTC patients even in second- and third-line therapy, with similar PFS and stable disease as best response. Bone and pleural metastases were the most refractory and liver lesions the most responsive to treatment.

Responses to Dasatinib as a Second- and Third-Line Tyrosine Kinase Inhibitor in Chronic Phase Chronic Myeloid Leukaemia Patients

2019 ◽  
Vol 142 (2) ◽  
pp. 79-86 ◽  
Author(s):  
Jiaqi Tan ◽  
Mengxing Xue ◽  
Jinlan Pan ◽  
Jiannong Cen ◽  
Xiaomei Qi ◽  
...  
Keyword(s):  
Chronic Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Chronic Phase ◽  
Molecular Response ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Third Line Therapy ◽  
Third Line ◽  
Dasatinib Treatment

We retrospectively evaluated the efficacy and safety of dasatinib among 48 Chinese patients with chronic phase chronic myeloid leukaemia. The proportions of patients achieving the optimal molecular responses at 3, 6, and 12 months, a major molecular response (MMR) rate and a complete cytogenetic response (CCyR) rate were 87.0, 87.0, 72.2, 45.8, and 72.7% for patients with dasatinib as second-line therapy, and 34.8, 34.8, 33.3, 20.8, and 46.2% as third-line therapy, respectively. A BCR-ABL1 transcript level on the International Scale (BCR-ABL1IS) of ≤10% at the initiation of ­dasatinib treatment was found to be associated with a higher probability of achieving MMR. Among patients with a ­BCR-ABL1IS higher than 10% at initiation of dasatinib treatment, dasatinib showed better performance as a second-line therapy than as a third-line therapy. The patients who achieved an optimal molecular response at 3 months had a superior cumulative incidence of MMR and CCyR compared with patients who failed to achieve such a response. Dasatinib induced considerable responses as a second-line treatment, especially in patients with a BCR-ABL1IS ≤10% at initiation of treatment, whereas the efficacy was limited in patients receiving third-line therapy with a BCR-ABL1IS >10% at the initiation of treatment.

scholarly journals Efficacy of tyrosine kinase inhibitors (TKIs) as third-line therapy in patients with chronic myeloid leukemia in chronic phase who have failed 2 prior lines of TKI therapy

Blood ◽  
2010 ◽  
Vol 116 (25) ◽  
pp. 5497-5500 ◽  
Author(s):  
Amr R. Ibrahim ◽  
Christos Paliompeis ◽  
Marco Bua ◽  
Dragana Milojkovic ◽  
Richard Szydlo ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Second Line ◽  
Line Therapy ◽  
Third Line Therapy ◽  
Third Line

Abstract We analyzed a cohort of 26 patients with chronic myeloid leukemia who had failed imatinib and a second tyrosine kinase inhibitor but were still in first chronic phase and identified prognostic factors for response and outcomes. The achievement of a prior cytogenetic response on imatinib or on second-line therapy were the only independent predictors for the achievement of complete cytogenetic responses on third-line therapy. Younger age and the achievement of a cytogenetic response on second line were the only independent predictors for overall survival (OS). At 3 months, the 9 patients who had achieved a cytogenetic response had better 30-month probabilities of complete cytogenetic responses and OS than the patients who had failed to do so. Factors measurable before starting treatment with third line therapy and cytogenetic responses at 3 months can accurately predict subsequent outcome and thus guide clinical decisions.

Efficacy of Tyrosine Kinase Inhibitors in Third Line Therapy in Chronic Phase Chronic Myeloid Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4051-4051 ◽  
Author(s):  
Elza Lomaia ◽  
Andrey Zaritskey ◽  
Vasily Shuvaev ◽  
Irina Martynkevich ◽  
Mikhail Fominykh ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Median Time ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Line Therapy ◽  
Third Line

Abstract Introduction. Overall survival (OS) of patients in chronic phase (CP) chronic myeloid leukemia (CML) dramatically increased in the era of tyrosine kinase inhibitors (TKI). Meanwhile nearly half of patients discontinue 1-st line Imatinib due to resistance or intolerance. Half of them subsequently failure treatment with second line TKI. It seems that 20-25% of CP CML patients need 3-d line therapy (TKI-3l). There are a few reports regarding durable outcome of TKI-3l. Materials and Methods. In our retrospective study 53 patients (20 male, 33 female) with CML CP treated either by Nilotinib 400 mg BID (n=18), Dasatinib 100 mg QD (n=33) or Bosutinib 500 mg QD (n=5) as TKI-3l were included. The median age at the time of diagnosis was 46 years (23-88 years). The main reason for previous TKIs discontinuation was resistance: 48/53 (91%) had failure of one and 42/53 (79%) patients had failure of both previous TKIs treatment. Median CML duration before TKI-3l was 55 months (2-314 months). Before TKI-3l mutation analysis was performed in 35 patients: 18 mutations were revealed in 16 (46%) patients including T315I mutation in 3 cases. At the moment of 3-d line TKIs therapy initiation, all patients were in CP and 43/53 (81%) had at least complete hematologic response (CHR), 8/53 (15%) patients had major cytogenetic response (MCyR) including 1 patient with complete cytogenetic response (CCyR). Results. At the time of analysis, the median duration of TKI-3l therapy was 21 months (1-67 months). No additional patients achieved CHR, but during observational time CHR was maintained nearly in all 40/43 (93%) patients with CHR at baseline. New cases of MCyR and CCyR were observed in 15/45(33%) and 11/52(21%) of patients, respectively. Median time to MCyR and CCyR was 3.4 (3-8) and 5.2 (3-13) months, respectively. Median duration of MCyR and CCyR was 9.3 (1-43) months and 4.5 (3-6) months, respectively. Patients with resistant mutations did not obtain any cytogenetic response. TKI-3l treatment was discontinued in 21 patients. Intolerance was the reason of treatment discontinuation in 5/53(10%) cases. Progression to accelerated or blastic phases during therapy or after discontinuation occurred in 8/53 (15%) patients. Median time to progression was 14.7 months (1-46 months). There were 13 deaths in overall group of 53 patients. Two-year OS in TKI-3l was 67%. All patients with MCyR were alive and preserved CP phase. Concluson: Our results showed that 20% of patients might obtain at least CCyR and benefit with TKIs as third line. Therefore, after two TKI lines patients, who are not eligible for allogeneic transplantation and without resistant mutations should be treated with one more line of TKI therapy. Disclosures Lomaia: Novartis: Consultancy. Zaritskey:University of Heidelberg: Research Funding; Novartis: Consultancy.

scholarly journals Cost-effectiveness of preemptive skin treatment to prevent skin-toxicity caused by panitumumab in third-line therapy for KRAS wild type metastatic colorectal cancer in Japan

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Munenobu Kashiwa ◽  
Ryo Matsushita
Keyword(s):  
Colorectal Cancer ◽  
Cost Effectiveness ◽  
Metastatic Colorectal Cancer ◽  
Skin Toxicity ◽  
Wild Type ◽  
Preemptive Treatment ◽  
Line Therapy ◽  
Third Line Therapy ◽  
Third Line ◽  
The Cost

Abstract Background Clinical management of skin-toxicity associated with the use of anti-Epidermal Growth Factor Receptor (EGFR) antibodies to treat colorectal cancer maintains quality of life of patients with colorectal cancer. Results of clinical trials have recommended the efficacy of prophylactic treatment, but the cost-effectiveness is unclear. This study examined the cost-effectiveness of preventive skin care for skin-toxicity caused by panitumumab in third-line therapy for KRAS wild type metastatic colorectal cancer from the perspective of the Japanese healthcare payer. Methods The data source was J-STEPP trial, which compared preemptive skin treatment with reactive treatment in third-line panitumumab therapy for KRAS wild type metastatic colorectal cancer in Japan. The costs and effectiveness of preemptive treatment was compared with reactive treatment in a 3-year time horizon using a 4-state partitioned survival analysis. The health outcome was quality-adjusted life-years (QALYs). The costs were 2020 revisions to the drug prices. The robustness of the model was verified by one-way sensitivity analysis and a probabilistic sensitivity analysis (PSA). A 2% annual discount was applied to the expenses and QALYs. Willingness-to-pay (WTP) threshold of 5 million JPY was used. Results Preemptive treatment had incremental effects of 0.0029 QALYs, incremental costs of 5300 JPY (48.6 USD), and incremental cost-effectiveness ratios (ICER) of 1,843,395 JPY (16,912 USD) per QALY. The variability of preemptive and reactive treatment costs for skin-toxicity and the disutility of skin-toxicity had a large impact on ICER. From PSA, the cost-effectiveness rate of preemptive treatment was 75.0%. Conclusions The cost to effectiveness of preemptive treatment to prevent skin-toxicity caused by panitumumab in third-line therapy for KRAS wild type mCRC is not high.

scholarly journals H2-antagonist in IgE-mediated type I hypersensitivity reactions: what literature says so far?

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Matteo Borro ◽  
Simone Negrini ◽  
Andrew Long ◽  
Sharon Chinthrajah ◽  
Giuseppe Murdaca
Keyword(s):  
Receptor Antagonist ◽  
Inflammatory Responses ◽  
Type I ◽  
Line Therapy ◽  
H2 Antagonist ◽  
Amino Acid Histidine ◽  
Third Line Therapy ◽  
Ige Mediated ◽  
Third Line ◽  
Type I Hypersensitivity

AbstractHistamine is a monoamine synthesized from the amino acid histidine that is well-known for its role in IgE-mediated anaphylaxis but has shown pleiotropic effects on the immune system, especially in order to promote inflammatory responses. H1-receptor antagonist are common drugs used in mild/moderate allergic reactions whereas H2-receptor antagonist are commonly administered in gastric ulcer but showed some properties in allergy too. The EAACI guidelines for diagnosis and treatment of anaphylactic reactions recommend their use as third-line therapy in adjunct to H1-antagonists. The purpose of this article is to produce a complete summary of findings and evidence known so far about the usefulness of H2-receptor antagonist in allergic reactons.

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