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Evaluation of the efficacy of levocarnitine in supporting
therapy in multiple myeloma
Ozoda ACHILOVA
1
, Gulchekhra MAKHAMADALIEVA
2
, Eldor ISKHAKOV
3
Republican Specialized Scientific Practical Medical Center of Hematology
Tashkent State Institute of Postgraduate Medical Education
ARTICLE INFO
ABSTRACT
Article history:
Received January 2021
Received in revised form
15 January 2021
Accepted 20 January 2021
Available online
01 February 2021
The accompanying therapy prescribed during the use of toxic
drugs helps patients to complete the treatment to the end, and
the doctor adheres to the treatment of the chosen line
The aim of the study
was to study the effect of levocarnitine
on blood biochemical parameters and on chemotherapy
tolerance.
Materials and methods.
The study was conducted in the stem
cell treatment department at Republican Specialized Scientific
Practical Medical Center of Hematology . Chemotherapy toxicity
was assessed according to WHO and NCIC standards.
Results.
In a comparative study, 30 patients receiving
chemotherapy for myeloma with varying degrees of toxicity
when fortecarnite (100 mg / kg / day) was added to standard
therapy for 2 months or more showed a significant positive
change in cytochemical parameters (Alanin transferase (ALT),
aspartat transferase (AST)), which allowed the authors
recommend metabolic correction to all patients receiving
chemotherapy, especially with 2nd and 3rd degree of toxicity.
2181-
1415/© 202
1 in Science LLC.
This is an open access article under the Attribution 4.0 International
(CC BY 4.0) license (https://creativecommons.org/licenses/by/4.0/deed.ru)
Keywords:
accompanying therapy,
levocarnitine,
toxicity assessment,
fortecarnitis,
metabolic correction.
1
PhD, hematologist of Republican Specialized Scientific Practical Medical Center of Hematology, Tashkent, Uzbekistan
E-mail:
2
PhD, hematologist of Republican Specialized Scientific Practical Medical Center of Hematology, Tashkent, Uzbekistan
E-mail: kuzieva79@mail.ru
3
Associate professor, DSc, Head of Department of «Hematology and Transfusiology», Tashkent State Institute of
Postgraduate Medical Education, Ministry of Health of the Republic of Uzbekistan, Tashkent, Uzbekistan
E-mail: dr.eldor@yahoo.com
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Levokarnitinni mieloma kasalligi bemorlarida yondosh
terapiyada ahamiyatini baholash
ANNOTASIYA
Kalit so
’
zlar:
qo'shma terapiya,
levokarnitin,
toksikani baholash,
fortekarnit,
metabolik tuzatish.
Toksik dorilarni qabul qilish paytida buyurilgan terapiya
bemorlarga davolanishni yakunlashiga yordam beradi va shifokor
davolanishni tanlangan yo'nalishda kuzatib boradi.
Tadqiqotning maqsadi levokarnitinning qonning biokimyoviy
ko'rsatkichlari va kimyoviy terapiyaga bardoshliligi ta'sirini
o'rganish edi.
Materiallar va uslublar.
Respublika ixtisoslashtirilgan ilmiy-
amaliy gematologiya tibbiyot markazi klinikasida urganildi.
Kimyoviy terapiyaning toksikligi JSST va NCIC standartlariga
muvofiq baholandi.
Natijalar. Qiyosiy tadqiqotlar davomida mieloma uchun toksik
darajasi har xil bo'lgan PCT bilan og'rigan 30 nafar bemorda 2 oy va
undan ko'proq vaqt davomida fortekarnit (kuniga 100 mg / kg)
standart terapiyaga qo'shilganda sitokimyoviy parametrlarda (ALT,
AST) sezilarli o'sish kuzatildi. Mualliflar kimyoviy terapiya qabul
qiladigan barcha bemorlar uchun metabolik tuzatishni tavsiya
etadilar, ayniqsa 2 va 3 darajali toksiklik bilan.
Оценка
эффективности
левокарнитина
в
сопроводительной терапии
при множественной миеломе
АННОТАЦИЯ
Ключевые слова:
Сопроводительная
терапия,
левокарнитин,
оценка токсичности,
фортекарнит,
метаболическая
коррекция.
Сопроводительная терапия, назначаемая при применении
токсичных препаратов, во многом помогает пациентам довести
лечение до конца, а врачу придерживаться терапии выбранной
линии
Целью
исследования
явилось
изучить
влияние
левокарнитина на биохимические показатели крови и на
переносимость химиотерапии.
Материалы и методы.
Исследование проводилось в
отделении по лечению стволовыми клетками при центре
Гематологии. Оценка токсичности химиотерапии проводилась
–
по стандартам ВОЗ и NCIC.
Результаты.
В сравнительном исследовании у 30 пациентов,
получающих ПХТ при миеломной болезни с различной
степенью токсичности при добавлении к стандартной терапии
фортекарнита (100 мг/кг/сутки) в течение 2 месяцев и более
отмечено
значимое
положительное
изменение
цитохимических показателей (аланин трансфераза (АЛТ
),
аспартат трансфераза (АСТ
)
), что позволило авторам
рекомендовать метаболическую коррекцию всем пациентам,
получающим ПХТ, особенно при 2
-
й и 3
-
й степени токсичности.
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Concomitant therapy prescribed when using toxic drugs, in many ways helps
patients to complete treatment, and the doctor to adhere to the therapy of the chosen line
[4, 5]. In the treatment of neurological, cardiological, nephrological diseases, the use of
targeted medications is repeated many times until remission is achieved. Hematological
and oncological diseases, all the more, are no exception [7,10].
At present, when conducting PCT courses, great importance is attached to the issues
of metabolic therapy as a significant pathogenetic link in almost all complications caused
by chemotherapy [1,2,7,10]. In this regard, the search for drugs with a general effect on
metabolism is relevant. One of these drugs is discovered by Russian scientists R. Krimberg
and V.S. Gulevich, carnitine is a natural compound, the metabolic functions of which are
associated with the transport of fatty acids into the mitochondria, where they are oxidized
with the release of energy ATP, modulation of the intracellular homeostasis of coenzyme
A in the mitochondrial matrix, detoxification of excess acetic and a number of other organic
acids, as well as participation in the process of glycolysis, exchange of ketone bodies and
choline [2,3,4,9]. In the presence of carnitine, free radical binding reactions occur, which
is manifested by a decrease in intoxication syndrome. Carnitine is found in all organs,
especially in tissues that require high energy supply - muscles, myocardium, brain, liver,
kidneys. The need for carnitine is individual (usually 200-500 mg per day for an adult),
and with mental, physical and emotional stress, diseases and functionally special
conditions (stress, pregnancy, breastfeeding, sports, etc.) 20 times. In patients receiving
chemotherapy, the need for carnitine increases due to an increase in oxidation products in
the div and an increase in the catabolic syndrome associated with the direct tumorlytic
effect of cytostatics [7,8,9]. Endogenous synthesis in an adult provides only about 10% of
the div's need for carnitine, and this requires vitamins C, B3, B6, folic acid, iron, a number
of amino acids and enzymes. With a deficiency of at least one of the components, carnitine
deficiency with its various systemic manifestations may develop. During chemotherapy,
the endogenous synthesis of carnitine decreases, which makes them vulnerable to
insufficient intake of exogenous carnitine from food, especially when there is a deficiency
in the diet of animal protein [1,2,4,7]. Despite the widespread use of carnitine in medicine
in the treatment of various diseases, the presented results of its use in correcting the side
effects of chemotherapy are insufficient. The normal diet covers half of the carnitine
requirement at best, so there is a clear need for additional sources of carnitine to meet
optimal physiological requirements. The natural L-stereoisomer of carnitine is biologically
active, therefore only L-carnitine, which is almost completely absorbed in the human
gastrointestinal tract, should be used as a food additive or drug [4,9]. The domestic
company "Rapid Solution" produces the drug "Fortecarnit" (INN LEVOCARNITINE) for
oral administration, containing a 20% aqueous solution of L-carnitine, which is identical
in chemical structure and biological activity to natural.
The aim of the study was to study the effect of levocarnitine on blood biochemical
parameters and on the tolerance of chemotherapy.
MATERIAL AND METHODS
The study was carried out in the department for stem cell treatment at hematology
center. The study involved 60 patients. The patients are divided into 2 groups of 30 people
each. Age ranged from 33-59 years old (on average 42 years old), men - 27, women -33.
Group 1 - 30 people who were prescribed standard concomitant therapy and levocarnitine
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at a dose of 100 mg / kg / day daily for 60 days. Group 2 - 30 people received standard
concomitant therapy without levocarnitine. The assessment of the toxicity of
chemotherapy was carried out according to the WHO and NCIC standards. Assessment of
hematological toxicity was carried out according to the results of weekly examination of
patients, as well as before each course of chemotherapy. Control of non-hematological
toxicity was carried out immediately before the administration of drugs and in the
intervals between courses of chemotherapy. At the start of chemotherapy, the patients
had an overall ECOG functional status of 0 to 2 and a life expectancy of at least 6 weeks. All
had satisfactory blood counts: neutrophils ≥1500 / mm3, platelets ≥100,000 / mm3,
creatini
ne less than 200μmol / l, hemoglobin more than 80 g / l, there were no concomitant
diseases in the stage of decompensation.
RESULTS AND DISCUSSION
The therapeutic effect was considered in 60 patients who received 135 courses of
chemotherapy. On average, 2 courses of chemotherapy per person. In a comparative
analysis of the toxicity of chemotherapy, nausea and vomiting were most often observed,
more in the group of patients treated without levocarnitine. In 2 (6%) cases, due to
vomiting, the chemotherapy course had to be postponed for 1 week.
Leukopenia was also more often observed in group 2, 9 (18%) patients were
prescribed colony-stimulating factors, in 3 (6%) the dose of cyclophosphamide was
reduced by 20%, the timing of chemotherapy did not change. The frequency and degree of
fever were more pronounced, and in 3 (10%) patients, chemotherapy was delayed by 1
week, and they received appropriate antibiotic therapy for the infectious syndrome. Grade
IV neutropenia occurred in 5 patients (18%), which led to the complete cancellation of the
target drug and its replacement with a second-line drug. Among other types of toxicity,
cystitis was observed in group 2 - in 2 (6.0%) patients who underwent symptomatic
treatment, the timing of chemotherapy did not change, and cardiotoxicity - in 1 (3%)
patient, the dose of borezomib was reduced by 30%. In the compared group, no such
phenomena were registered (Table 1).
The use of levocarnitine at a dose of 100 mg / kg / day reduced dyspeptic complaints
in patients by 30%. In the 2nd group, polychemotherapy courses did not have to be
postponed. The length of hospital stay decreased by 3-4 days. In addition, in patients of
group 1, with the introduction of chemotherapy drugs, an increase in ALT and AST was
never recorded. On the contrary, in patients of the 2nd group, in all cases, there is a
transient increase in ALT (47-52 U / L) and AST (51-61 U / L) in 15 patients (50%), and a
persistent increase in enzymes of more than 60 U / L in 5 (20%).
Table 1.
Comparative assessment of the toxicity of chemotherapy in groups 1 and 2.Tab
Toxicity type
Toxicity level according to WHO criteria
I
II
III
IV
Nausea
12
19
4
5
1
2
-
1
Vomiting
5
12
2
3
1
1
-
-
Leukopenia
1
3
-
1
-
1
-
-
Stomatitis
-
2
-
2
-
-
-
-
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Anemia
-
14
-
4
-
2
-
-
Thrombocytopenia
-
1
-
-
-
-
-
-
Neutropenia
-
-
-
-
-
-
-
Neuropathy
5
15
-
-
-
-
-
-
Cystitis
-
2
-
-
-
-
-
-
Cardiotoxicity
-
1
-
-
-
-
-
-
The patient's physical health and the degree of his quality of life were assessed by a
questionnaire based on the OPCW questionnaire. When questioning, it was found that a
group of patients receiving planned chemotherapy with the use of high doses of
dexamethasone, who received Fortecarnit at 100 mg / kg / day for 60-75 days as part of
concomitant therapy, showed an improvement in physical condition by 1.6 times
compared with the control group ...
Conclusion. In a comparative study, in 30 patients receiving PCT for multiple
myeloma with varying degrees of toxicity, when added to standard therapy fortecarnite
(100 mg / kg / day) for 2 months or more, a significant positive change in cytochemical
parameters (ALT, AST) was noted, which allowed the authors recommend metabolic
correction to all patients receiving chemotherapy, especially with the 2nd and 3rd degree
of toxicity. In addition, the addition of levocarnitine to concomitant therapy can reduce
complications after chemotherapy, improve drug tolerance and dyspeptic complaints.
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