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Роаккутан при нейробластоме |
Konstantin1
Ранг: Гость
Ф.И.О.: 1
Всего сообщений: 2
|  Опубликовано: 04-02-2007 22:00
Уважаемые доктора.
На чем основывается применение роаккутана в терапии нейробластов у детей? Ведь это препарат для лечения угревой сыпи. Препарат дорогой и с массой противопоказаний и побочных эффектов.
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Pankina
Консультант
Ранг: Легенда
Ф.И.О.: 1
Адрес: Россия, Москва
Всего сообщений: 2758
| ! Сообщение официального консультанта форума
Опубликовано: 05-02-2007 18:58
Детская онкогематология здесь.
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terro
Консультант
Ранг: Старожил
Ф.И.О.: 1
Профессия: врач
Специальность: онкогематология
Адрес: Украина
Всего сообщений: 218
| Опубликовано: 08-02-2007 02:05
Это скоре вопрос по детской онкологии речь идет о терапии нейробластом на этапе поддерживающей терапии и терапии после ауто трансплантации в современных протоколах действительно рекомендован прием роакутана. Собственно там же есть обоснование его применения и ожидаемой эффективности однако очень трудно обьяснить это в популярной форме доступной для людей без специального образования
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Konstantin1
Ранг: Гость
Ф.И.О.: 1
Всего сообщений: 2
| Опубликовано: 16-02-2007 22:55
Уважаемый terro, в аннотации к препарату применение в онкологии не упоминается. Если не затруднит, расшифруйте действие роаккутана для данной категории больных. Спрашивает врач-педиатр.
[ Это сообщение было отредактировано 2007-02-16 22:59 пользователем/модератором Konstantin1 ]
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terro
Консультант
Ранг: Старожил
Ф.И.О.: 1
Профессия: врач
Специальность: онкогематология
Адрес: Украина
Всего сообщений: 218
| Опубликовано: 20-02-2007 00:14
Привожу выдержку из обоснования применения и изучения действия цисретиноевой к-ты у детей с нейробластомами, а что онколог который назначил роакутан ничего не обьяснил?
Retinoids are a class of compounds consisting of both natural and synthetic
substances structurally related to vitamin A (retinol). They can inhibit cell
proliferation and induce differentiation and apoptosis in many cell types during normal
development as well as in cancer cells propagated in tissue culture (1-3). Two of the
most clinically useful retinol derivatives are 13-cis-retinoic acid (13-cis-RA) and all-
trans retinoic acid (ATRA). Despite the fact that these two retinoids are isomers, they
exhibit contrasting efficacy, toxicity and pharmacokinetics in clinical studies (4-6).
A phase I study in 51 children with high risk neuroblastoma indicated that an
intermittent schedule of high dose 13-cis-RA after bone marrow transplantation had
minimal toxicity, with the maximal tolerated dose (MTD) being determined as 160
2
mg/m
in two equally divided doses daily (6). This dose of 13-cis-RA resulted in the
achievement of serum levels known to be effective against neuroblastoma cell lines in
vitro and the clearing of tumour cells in bone marrow, as determined by morphological
assessment, was observed in 3 out of 10 patients. The dose-limiting toxicities of 13- cis-RA consisted of hypercalcemia and combinations of skin, gastrointestinal and
haematopoietic toxicities which resolved after 13-cis-RA was discontinued.
Pharmacokinetic studies performed in 31 patients entered into the Phase I trial
of 13-cis-RA in children showed significant interpatient and intrapatient variability in
peak serum levels (mean peak serum 13-cis-RA concentration : 7.2 5.3µM; trough
concentration : 4.1 2.7µM). These studies also suggested a correlation between peak
serum concentrations above 10µM and a higher incidence of grade 3 and 4 toxicities in
patients (5,6).
Results from this Phase I study led to a larger prospective, randomized study
with 13-cis-RA, based on the MTD obtained from the phase I study, being carried out
by the Children’s Cancer Group (CCG) in children with high risk neuroblastoma in the
USA. This study was designed to i) compare a combination of myeloablative
chemotherapy, total body irradiation and transplantation of autologous bone marrow
purged of cancer cells versus intensive nonmyeloablative chemotherapy, and ii)
determine whether treatment with 13-cis-RA following transplantation or
chemotherapy further improved event-free survival (7).
The CCG study included a total of 379 patients in the first randomization,
comparing myeloablative therapy and bone marrow transplantation with continuation
chemotherapy, and 258 patients in the second randomization, comparing 13-cis-RA
treatment with no further therapy. Eighty-five percent of these patients had stage 4
neuroblastoma and were older than one year of age at diagnosis. The mean event-free
survival rate three years after the first randomization was significantly better among
the 189 patients who were assigned to undergo transplantation than among the 190
patients assigned to receive continuation therapy (34 4% vs. 22 4%, P=0.034). For
the second randomization, treatment of patients with 13-cis-RA was shown to result in
a significantly better event-free survival rate three years after randomization than no
further patient treatment (46 6% vs. 29 5%, P=0.027). Treatment with 13-cis-RA
appeared to benefit patients who received either a bone marrow transplant or
continuation chemotherapy and there was no evidence of an interaction between the
two randomization treatments. The estimated event-free survival three years after the
second randomization for the patients assigned to receive myeloablative therapy/transplantation followed by 13-cis-RA was 55 10%, as compared with 18
6% for those assigned to chemotherapy alone.
Since the publication of these results, 13-cis-RA has become an integral part of
the treatment of high-risk neuroblastoma. However, despite these initial successes, the
majority of children with high-risk neuroblastoma still succumb to the disease.
Optimisation of the clinical use of 13-cis-RA could lead to a substantial improvement
in outcome for this disease, as emphasised by the fact that a European Neuroblastoma
Study Group trial (ENSG 4), showed no survival advantage of low dose oral 13-cis-RA
2
(0-75mg/kg/day; 22.5mg/m /day), given as continuous treatment for 4 years after
myeloablative therapy ( . 13-cis-RA is administered orally and reliable administration
depends on the practicalities of administration and on compliance. When absorbed, the
drug may be subject to first-pass metabolism and subsequent plasma (and tumour)
concentrations will depend on the rate of metabolism to the inactive 4-oxo metabolite.
A number of cytochrome P450 (CYP) enzymes have been identified as playing
a role in the metabolism of 13-cis-RA (9, 10). CYP2C8 is most important in terms of
activity and level of expression in the liver. 13-cis-RA impairs the metabolism of the
CYP2C8 substrate paclitaxel both in vitro and in patients (11). Genetic
polymorphisms in the CYP2C8 gene have been described (12) which result in a lower
rate of paclitaxel metabolism and are commonly seen in a Caucasian population (12,
13). Thus, genetic variation in CYP2C8 activity could underlie individual differences
in 13-cis-RA metabolism and bioavailability. The foetal isoform CYP3A7, which is
expressed post-natally in a significant number of individuals, also metabolizes 13-cis-
RA (10). The expression of CYP3A7, and thus the contribution of this isoform to 13-
cis-RA metabolism, may be predicted by genotyping (14, 15) in a paediatric
population. A further aspect of 13-cisRA metabolism is glucuronidation, both of the
parent drug and of 4-hydroxy-metabolites. This conjugation may be mediated by
UGT1A1 or UGT2B7 (16), both enzymes that are subject to genetic polymorphisms
(17).
A study being run in the UK (UKCCSG Study PK 2000 0, designed to
investigate variation in 13-cis-RA pharmacokinetics within and between courses of
treatment, has currently recruited 20 patients. Preliminary data from this study have
indicated that plasma concentrations of 4-oxo-13-cis-RA can accumulate to exceed
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 Уважаемые пациенты! Мы можем ответить на Ваши вопросы, мы можем подсказать Вам, что лучше сделать в конкретной ситуации, но помните, что ни одна виртуальная консультация не заменяет очный визит к врачу. |
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