Adverse anaphilactoid reaction of oxaloplatin

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NOTAS CLÍNICAS
Adverse anaphilactoid reaction
of oxaloplatin
a
a
a
b
Uriel Bohn , José Aguiar , David Aguiar and Rodolfo Castillo
a
Servicios de Oncología Médica y
b
Alergia. Hospital General de Gran Canaria Dr. Negrín. Las Palmas de Gran Canaria.
Reacción anafilactoide con oxaloplatino.
Caso clínico
2002;4(3): 150-60.
El oxaloplatino (L-OHP) es un análogo de
tercera generación del platino utilizado en
pacientes con carcinoma colorrectal. Describimos el caso de un paciente varón de
50 años sin antecedentes de interés en
estadio IV (pulmón e hígado) que recibió
en 1999 6 ciclos de 5FU-LV, 6 ciclos de
5FU-oxaloplatino y 6 ciclos de 5FU-CPT11
sin respuesta. En febrero de 2001 por
progresión pulmonar recibió quimioterapia
con oxaloplatino y ratiltrexed. Tres semanas más tarde durante la administración del oxaloplatino presentó un cuadro
de reacción anafilactoide que se resolvió
con actocortina. A las 24 horas, previa
protección con corticoides, al paso de
escasas gotas de oxaloplatino inició un
c
u
a
d
r
o
similar al descrito, por lo que se suspendió su administración. Los niveles de IgA
(482 mg/dl) y de IgE total (647 UI/ml) se
encontraban elevados, lo que indicó que se
trataba de una reacción anafilactoide de
hipersensibilidad tipo I mediada por IgE.
Sin un tratamiento inmediato, el cuadro
de anafilaxia avanza produciendo una gran
morbilidad con shock, fallo multiórgano y
muerte.
El
uso
de
esteroides
antes de la administración de oxaloplatino
previene este tipo de reacciones adversas.
Palabras clave: oxaloplatino, reacción, anafilaxis.
Bohn U, Aguiar J, Aguiar D, Castillo R. Adverse anaphilactoid reaction of oxaloplatin. A case report. Rev Oncol
Correspondence: Dr. Uriel Bohn S.
Servicio de Oncología Médica.
Hospital General de G. C. Dr. Negrín.
Barranco de La Ballena, s/n.
35020 Las Palmas de Gran Canaria.
E-mail: uriel@idecnet.com
Received 28 August 2001; revised 13 November 2001; accepted
16 November 2001.
CASE DESCRIPTION
Oxaloplatin (L-OHP) a third-generation cisplatin analo1,2
gue
has been used in more then 1,700 patients as a
single agent and in combinations with fluoropiridines
(5FU) and folinic acid (FA) in colorectal carcinoma, in the
3
contest of clinical trials or compassionate use programs .
The
adverse
grade
3-4 events most cited were haematological, gastro-intestinal and neurotoxicity, all of them in a low percent de4-6
gree . Amifostine (Ethyol) is an analogue of cysteamine
that selectively protects normal tissues of various organs
from
the
effects of radiation and multiple cytotoxic chemotherapeutic drugs. Raltitrexed a thymidylate synthase inhibitor,
have well known toxicity profile with grade 2 diarrhoea
and mild neutropenia is used as a single agent or in combination with 5FU, CPT11 or oxaloplatin.
We describe a case of a 50 years old man without history
of illness or allergies. In July 1999 he had a bowel obstruction and a right hemicolectomy was performed and
diagnosed of colonic adenocarcinoma grade 2 Stage IV
(pT3 pN1 M1). The chest Rx, liver ecography and total
body CT showed multiple small bilateral lung and one hepatic metastases. From September 1999 to August
2000, he received three lines of polychemotherapy without response: 6 cycles of 5FU-LV (Mayo Clinic), 6 cycles
of 5FU-oxaloplatin (Gramont) and 6 cycles of 5FU-CPT11.
Six months later a Chest Rx did show an increased number
of lesion and the liver ecography did not show any change. In February 13-01 with an ECOG 0, the patient received dexametasone 20 mg/iv, ondansetron 16 mg/iv, ami2
fostine 1.480 mg (740 mg/m ) in 20´ followed by
2
oxaloplatin 260 mg (130 mg/m ) in 2 hours and ratiltre2
xed
6
mg
(3
mg/m )
45´ later in 20´. Hipotension during the administration of
amifostine with spontaneous recovery was observed as
usual. Three weeks later hipotension with amifostine was
seen again and during the oxaloplatin infusion the patient
had an adverse reaction with cough, disphonia, white secretions, stridor, edema of the face and upper chest rash.
Actocortin 100 mg/iv and polaramine 6 mg/iv were administered with a progressive recovery. Twenty-four hours
later, with a corticoids protection a few drops of oxaloplatin were enough to begin the cough again. The infusion
was stopped and one hour later the ratiltrexed was given
without
any
adverse
Rev Oncol 2002;4(3):159-60
159
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BOHN U, AGUIAR J, AGUIAR D, ET AL. ADVERSE ANAPHILACTOID REACTION OF OXALOPLATIN. A CASE REPORT
effect.
3
The blood test showed: leukocytes: 9.1 × 1 0 /ul. Neu3
trophi-les 69.9%. Lymphocites: 1.6 × 1 0 /uL. Eosinophiles:
0.4
×
3
3
1 0 /ul. Hb: 12.5 Gr. Platelets: 372 × 1 0 /ul. GGT: 69 U/l.
LDH: 878 U/l. Fe: 25 mg/dl. IgG: 1,430 mg/dl. IgA: 482
mg/dl. IgM: 224 mg/dl. Total IgE: 647 UI/ml (14-120
UI/ml).
The value of IgA was elevated and the total IgE was very
high.
7
There have been reported one anaphylactic case and one
8
idiosyncratic reaction with the use of oxaloplatin . In our
case the chronology of issues seems to be related with an
anafilactoid reaction type I immune hypersensitivity reaction
mediated by IgE, which induces mast-cell activation. The
reaction is produced by an escalating release of mediators
from mast cells and basophils. Mast cell and basophil activation is most usually initiated when specific antigen
binds to and cross-links preattached surface IgE molecules. The sequence of events in immediate hypersensitivity
stars with production of ice by B-cells in response to the
first exposure to an antigen; binding of the IgE to specific
Fc receptors on the surfaces of masts cells and basophils,
and interaction of re-introduced antigen with the bound
IgE, leading to activation of the mast cells and basophils.
160
IgE and eosinophil-mediated immune reactions are dependent on the activation of CD-4 helper and T-cells of the
T H 2 subset. The cytokines produced by TH 2 cells are responsible for inmediated type hypersensitivity.
Without an immediate treatment, anaphylaxis goes along
with great morbidity (shock, multiple organ failure) and
9
mortality . However, the steroid protocol must be administered before oxaloplatin is given in order to prevent adverse effects.
Key words: oxaloplatin, reaction, anaphilaxis.
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