buenos dÍas good morning bonjour. tolerance of imatinib dasatinib and nilotinib in the treatment of...
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GREETING
BUENOS DÍASGOOD MORNING
BONJOUR
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Tolerance of Imatinib Dasatinib and Nilotinib in the treatment of Chronic Myeloid Leukemia.
International Conférence on Toxicogenomics and Drug Monitoring and European Pharma Congress
August 25-27, 2015 Valencia, Spain
University Badji Mokhtar Annaba, Algeria
Annaba Medical College
Départment of Pharmacy
Chemistry Laboratory Therapeutic
Presented by
Dr. SOUDANI.W Chemistry Laboratory Therapeutic, Annaba, Algeria
Co-authors: Pr. DJAFER.R2, Dr. DJEDDI.H3, Dr. BOUGHRIRA.S3, Pr. GRIFFI .F3.
2: Service of Toxicology CHU Annaba, Algeria 3: Service of Hematolgy CHU Annaba,Algeria
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Introduction
The objective searched in the use of the anti-cancer treatment is to reach tumoral cells
in order to destroy them in a way as selective as possible, while operating one or more
targets, all this explains the multiplicity of the research undertaken in the field of
cancerology. Progress of molecular biology has allows the emergence of different therapeutic
approaches which deeply do not affect the operation of the healthy cells: immunizing
defenses of the organization, cellular differentiation, the angiogenesis and the apoptosis
constitute the principal explored ways.
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However, these ways are generally unbalanced by surexpression of a
protein having a strong activity tyrosin kinase, this led to the marketing of anti-
cancer non cytotoxic: Imatinib (Imatib®,Glivec®) first inhibitor of
receiver tyrosin kinase, this discovery was followed by the introduction of
other molecules of the same classe Dasatinib, Nilotinib,…
Introduction
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Anticancer treatment
Indicate means used in the treatment of cancers, which interfere with the cellular cycle, either by modifying the structure of the DNA, or by disturbing the proteinic synthesis
They involve the reduction in the tumoral cells by two processes
Antimitotic effect cytotoxic effect
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Hormone therapy Immunotherapy
Chemotherapy
Targeted Therapy
Anticancer Treatment
Anticancer treatment
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Targeted Therapy
The targeted molecular therapies indicate antitumor molecules able to inhibit a oncogenic way directly implied in the carcinogenesis and the progression of the tumoral cells. They aim at cellular events playing a main function in carcinogenesis, like the proliferation initiated by receivers tyrosin kinase of growth factor, and the angiogenesis.
Their targets can be membrane (EGFR, HER-2), cytoplasmic (mTOR), or present in the extracellular medium (VEGF).
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Targeted Therapy
Glycoproteins obtained starting from a cellular clone and recognizing specifically only one type of antigen fixed on a cell or a foreign protein.
Block the activity tyrosin kinase of a receiver or a cytoplasmic protein essential to the transduction of the signal of proliferation.
Monoclonal antibodies
Tyrosin kinase inhibitors
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Tyrosin Kinase Inhibitors
They block the activity tyrosin kinase of the receiver HER2.
They block the activity tyrosin kinase of many receivers. Antiangiogénic, Antiproliférative and proapoptotic action.
Monocibles Tyrosin Kinase Inhibitors
Multicibles Tyrosin kinase Inhibitors
Imatinib, Dasatinib, Nilotinib,,,Gefitinib, Erlotinib,,,
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Imatib®
, Glivec®,
Tasigna®
Sprycel®
Imatinib Nilotinib Dasatinib
Tyrosin Kinase Inhibitors
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Mode of action of Tyrosin kinase inhibitors
Tyrosin Kinase Inhibitors
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Objectives Principal objective : To evaluate the tolerance with the Inhibitors of Receivers Tyrosin Kinase (ITK) among cancer patients.
Secondary objective : To determine the carcinogenic risk factors among these patients.
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DESCRIPTIVE RETROSPECTIVE STUDY
17 men 16 women33 cancer patients
Material & Méthods
Period: From December 2012 to May 2013
Service of Hematology CHU ANNABA, ALGERIA
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Material & Méthods
Harvest of the Data
Data Analysis
• Information were collected on:
Monitoring sheets of the patients.
biological assessments.
• Cards of investigations were seized on Excel 2010.
• The data were expressed as a percentage, and averages.
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RESULTSSexe of cancer patients
male sexfemale sex
52% 48%
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Age of cancer patients
0-15 15-30 30-45 45-60 60-750
2
4
6
8
10
12
14
0%
40%
15%18%
27%
Median age of 45 years and two extremes 17 years and 72 years
RESULTS
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Professional situation
RESULTS
workers full time
workers partial time
reprocessed unemployed0
10
20
30
40
50
60
%21% 21%
3%
55%
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Geographical area
42 %
12 %
18 %
9 %
12 % 6 %
Annaba Guelma TébessaSkikda Souk-ahras Sétif
RESULTS
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Pathological antecedents
RESULTS
hematologic disorders
infections
diabete
gyneacological disorders
asthma
0% 1% 2% 3% 4% 5% 6% 7% 8% 9%
%
3%
3%
3%
9%
9%
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Carcinogenic factors
RESULTS
3%12%
geneticsprofessional exposurenone
85%
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All the treated cases had a Chronic Myeloid
Leukemia (CML) which accounted for 100% of the
patients.
RESULTSCancer
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Therapeutic protocols
RESULTS
Imatib Glivec Sprycel Tasigna0
10
20
30
40
50
60
without chemotherapyafter chemotherapy
12%
55%
9%3%
12%15%
21%
12%
Imatinib Imatinib Dasatinib Nilotinib
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Symptomatic Treatment
RESULTS
antigouty
antibiotics
antihypertensseurs
antiacid
antidiarrheal
antalgics
antiinflammatory
antispasmodic
coagulants
iron
vitamins+Ca
0 5 10 15 20 25 30 35
%
35%
13%
11%
8%
11%
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Tolerance to the Tyrosin Kinase Inhibitors
RESULTS
Imatib Glivec Sprycel Tasigna0
10
20
30
40
50
60
70
80
90
100
specific effectscommons effectscomplications
39% 39%
91%
57%
86%
14%
50%
67%
36%
54%
Imatinib Imatinib NilotinibDasatinib
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RESULTS
myalgia
oedema
osseous pain
hypertention
heamorrhage
tachycardia
hépatomégaly
0 5 10 15 20 25 30
%
30%
22%
22%
9%
Specific effects of Imatinib: Imatib®
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RESULTS
CNS.disorders
gastric disorders
cutaneous disorders
asthenia
anorexia
fall of hair
psychic disorders
0 10 20 30 40 50 60 70 80
%74%
57%
35%
35%
Communs effects of Imatinib: Imatib®
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Complications of Imatinib: Imatib®
RESULTS
ear-stomach pains
thoracic pain
colopathy
major asthenia
0 2 4 6 8 10 12 14
13%
9%
9%
9%
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Specific effects of Imatinib:Glivec®
RESULTS
myalgia
oedema
hepatic cytolysis
anaemia
tachycardia
0 5 10 15 20 25 30
%
29%
14%
14%
14%
14%
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Communs effects of Imatinib :Glivec®RESULTS
asthenia
gastric disorders
cutaneous disorders
CNS disorders
anorexia
psychic disorders
0 10 20 30 40 50 60 70 80
%
71%
29%
29%
14%
14%
14%
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Only one case having received hydroxyurée (Hydrea®)
as a chemotherapy in first intention then Imatinib: Glivec®,
which developed a colopathy with a respiratory allergy
Complications of Imatinib :Glivec®
RESULTS
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Specific effects of Dasatinib:Sprycel®
RESULTS
tachycardia
osseous pain
hemorroides
0% 2% 4% 6% 8% 10% 12% 14% 16% 18%
%
17%
17%
17%
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RESULTSCommuns effects of Dasatinib:Sprycel®
Asthenia
gastric disorders
cutaneous disorders
anorexia
0 5 10 15 20 25 30 35 40 45 50
%50%
33%
33%
17%
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RESULTSSpecific effects of Nilotinib:Tasigna®
anaemia
myalgia
hepatic cytolysis
osseous pain
hematological disorders
ictère
0 2 4 6 8 10 12 14 16 18
%
18%
9%
9%
9%
9%
9%
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RESULTSCommuns effects of Nilotinib: Tasigna®
gastric disorders
cutaneous disorders
asthenia
anorexia
0 5 10 15 20 25 30
%
27%
27%
9%
18%
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DISCUSSION
In our series thirty-three 33 cases, all the treated cancer patients had
Chronic Myeloid Leukemia CML, which accounted for 100% of the cases, the
frequency of each sex was half of the total manpower of our series.
The age bracket of the adult patients (15-60) years was the prevalent slice
85% with a peak for those having an age from 45 to 60 years with 40%, the
majority of these adults are unemployed, which explains the prevalence of
cancer at this population.
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The unemployed represented half of the total manpower with a
frequency of 54%, the stress pulled by the unemployed could be regarded as
a factor predisposing to cancer which is added to the other noted
carcinogenic factors ( the genetic factor at 4 cases and the professional
exposure at one case).
DISCUSSION
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The antigoutty medication were prevalent as symptomatic treatment
with a frequency of 35%, this is explained by the increase in the uric acid ;
principal biological Undesirable effect of Imatinib.
Then the antiacids (13%), then antihypertenseurs and coagulants in third
position (11%), this to prevent or correct the undesirable effects like the
hypertension, heartburn, and haemorrhage. this difference in frequencies is
dependent on nature and the frequency on the noted undesirable effects.
DISCUSSION
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The study of the tolerance showed that Imatinib: Glivec® gave only one
case with complications colopathy and respiratory allergy; with
disappearance of the osseous pains and the arterial hypertension wich was
obtained with Imatinib: Imatib®; what confirms a good tolerance of the
specialty of Glivec® compared to Imatib®.
DISCUSSION
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We did not note any complication for Dasatinib and Nilotinib, with
reduction in the specific effects (Dasatinib gave 17% of the osseous pains,
Nilotinib 9% of osseous pains and 9% of myalgia), reduction in the asthenia
(33% for Dasatinib and 9% for Nilotinib); this testifies to a better tolerance
of the new Tyrosin Kinase Inhibitors Dasatinib and Nilotinib compared to the
molecule of reference Imatinib (Imatib®, Glivec®).
DISCUSSION
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According to the got results, We noted a good
specificity of the undesirable effects of each Tyrosin
kinase Inhibitor such as : osseous pains 30%, arterial
hypertension 22%, an oedema (syndrome hand-foot) 9%
for Imatinib: Imatib®, and anaemia with 18% for Nilotinib
Tasigna®.
We noted the tolerance of the speciality of Glivec®
compared to Imatib® and a better tolerance of the new
Tyrosin Kinase Inhibitors Dasatinib and Nilotinib compared
to the molecule of reference Imatinib (Imatib® or
Glivec®).
CONCLUSION
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Inspide of a limited manpower, the results got concerning nature and the frequency of the undesirable and toxic effects are well correlated with those announced in the reviews of literature.
Through these data we raise the interest of selection of the therapeutic protocols and the importance of a strict monitoring of the undesirable and toxic effects of targeted therapy.
We underline the role of the responsible authorities of health which must encourage the production of expensive medication, in order to improve the dispensation of new targeted therapy, which makes it possible to ensure the best taken in charge of the cancer patients.
CONCLUSION
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THANK’S
GRACIAS
MERCI
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