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( the Editor:)Tj
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0.0977 Tw
[(A 20-year)19.7(-old woman was diagnosed in April)]TJ
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0.0002 Tc
0.1248 Tw
(2000 with a low-grade intraabdominal leiomyosar-)Tj
T*
0 Tc
0.1014 Tw
[(coma. The tumour was sur)17.8(gically resected. In June)]TJ
T*
0.0318 Tc
0.0931 Tw
(2002, she presented with progressive disease in)Tj
T*
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(lung, liver and unresectable multiple implants in pe-)Tj
T*
0.0112 Tc
0.1137 Tw
[(ritoneum. c-Kit \(CD1)36.8(17\) was immunohistochemi-)]TJ
T*
0 Tc
0.0261 Tw
[(cally assessed in the initial sur)17.8(gical sample, with re-)]TJ
T*
0.063 Tw
(sults negative. She received six cycles of doxorubi-)Tj
T*
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(cin iv \(50 mg/m)Tj
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0 Tw
(2)Tj
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-0.0001 Tc
0.0668 Tw
[(day 1, every 21 days\) plus ifosfa-)]TJ
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0 Tc
0.097 Tw
(mide iv \(2 g/m)Tj
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0 Tw
(2)Tj
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0.097 Tw
[(over 1 hour infusion, on days 1-3,)]TJ
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0.0073 Tc
0.1177 Tw
(every 21 days\), with a stabilization of the tumour)Tj
T*
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T*
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T*
0.0283 Tc
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(ascites. High doses ifosfamide was initiated \(12)Tj
T*
0 Tc
0 Tw
(g/m)Tj
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(2)Tj
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[(iv)64.9(, over 24 hours infusion, on days 1-5, every)]TJ
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0.0467 Tw
[(21 days\). Antiemetic prophylaxis consisted of 8 mg)]TJ
T*
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[(iv of ondansetron prior to chemotherapy)64.8(. She did)]TJ
T*
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0 Tw
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0.0509 Tw
(About 24 hours after the beginning of the second)Tj
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T*
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0.1033 Tw
(somnolence, with incoherence and disorientation)Tj
T*
0.0057 Tc
0.1193 Tw
[(\(neurocortical toxicity grade 3 of National Cancer)]TJ
T*
0.0341 Tc
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[(Institute-Common T)69.8(oxicity Criteria\). Peripheral)]TJ
T*
0 Tc
0.0751 Tw
[(blood counts and smear)39.8(, electrolytes, globulin, bili-)]TJ
T*
0.007 Tw
[(rubin \(total and direct\), alkaline phosphatase, SGPT)74(,)]TJ
T*
0.0229 Tc
0.102 Tw
(SGOT and prothrombin were normal. Creatinine)Tj
T*
0.0197 Tc
0.1053 Tw
[(clearance was 60 ml/min and serum albumin 2.8)]TJ
T*
0.0206 Tc
0.1044 Tw
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T*
0.0059 Tc
0.119 Tw
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T*
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[(fuse slowness consistent with metabolic encephalo-)]TJ
T*
0 Tw
[(pathy)64.9(.)]TJ
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0.0541 Tw
(50 mg iv methylene blue \(MB\) was administered)Tj
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0.0042 Tc
0.1208 Tw
(immediately to the patient, and repeated every six)Tj
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0 Tc
0.0169 Tw
(hours. One day later the signs of encephalopathy di-)Tj
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0.0009 Tc
0.1241 Tw
(sappeared. Our patient received prophylactic intra-)Tj
T*
0 Tc
0.0069 Tw
(venous with MB in a dose of 50 mg four times daily)Tj
T*
0.0245 Tw
[(for the next cycles, and no further episode of neuro-)]TJ
T*
0 Tw
(logical toxicity was noted. )Tj
0.9767 -1.1818 TD
0.0858 Tw
(Ifosfamide is an alkylating agent used in the tre-)Tj
-0.9767 -1.1818 TD
0.0024 Tc
0.1225 Tw
(atment of many solid tumors, including soft-tissue)Tj
T*
0.0343 Tc
0.0906 Tw
(sarcomas. It toxicity profile is characterized by)Tj
T*
0 Tc
0.0788 Tw
[(myelosuppression and urotoxicity)64.9(. Ifosfamide is re-)]TJ
T*
0.0789 Tw
(latively well tolerated, but has been responsible for)Tj
T*
0.0091 Tc
0.1158 Tw
(life-threatening toxicities such ifosfamide-induced)Tj
T*
0.007 Tc
0.1179 Tw
(encephalopathy \(IIE\))Tj
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0 Tc
0 Tw
(1)Tj
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0.007 Tc
0.118 Tw
(. This syndrome develops in)Tj
-9.0301 -1.1818 TD
0.043 Tc
0.082 Tw
[(10 to 15% of patients exposed to the drug and)]TJ
T*
0.001 Tc
0.1239 Tw
[(usually disappears after stopping therapy)64.8(, although)]TJ
T*
0 Tc
0 Tw
(some patients die without recovery)Tj
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(2)Tj
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(. )Tj
-13.3182 -1.1818 TD
0.0649 Tw
[(It occurs more frequently when the drug is given)]TJ
-0.9767 -1.1818 TD
0.0545 Tw
[(at intravenous high doses with short infusions time,)]TJ
T*
0.0083 Tc
0.1166 Tw
(and in patients with poor performance status, low)Tj
T*
0 Tc
0.047 Tw
(serum albumin and creatinine clearance)Tj
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0 Tw
(3)Tj
11 0 0 11 488.7197 283.6536 Tm
0.047 Tw
(. No cumu-)Tj
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0.0102 Tc
0.1148 Tw
[(lative-dose neurotoxic ef)17.8(fects have been reported,)]TJ
T*
0.0298 Tc
0.0952 Tw
(but re-treatment may again precipitate the same)Tj
T*
0.0132 Tc
0.1118 Tw
(acute toxicity manifestations. The clinical picture)Tj
T*
0.0023 Tc
0.1227 Tw
(can range from mild somnolence or agitation over)Tj
T*
0 Tc
0.0986 Tw
(confusion or hallucinations to deep coma and even)Tj
T*
0 Tw
(the death)Tj
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(1)Tj
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(. )Tj
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0.0218 Tc
0.1031 Tw
[(The exact mechanisms of IIE are unknow)64.8(, but)]TJ
-0.9767 -1.1818 TD
0.011 Tc
0.1139 Tw
(one or more metabolites of ifosfamide that are in)Tj
T*
0 Tc
0.019 Tw
[(high quantities may be the cause of the toxicity)64.9(. Ch-)]TJ
T*
0.0272 Tw
(loroethylamine may be the principal neurotoxic me-)Tj
T*
0.0385 Tc
0.0865 Tw
(tabolite involved. Chloroethylamine conjugates)Tj
T*
0 Tc
0.0669 Tw
(with cystein forming thialysine which can be meta-)Tj
T*
0.039 Tw
(bolized to thialysine ketimine. The latter can inhibit)Tj
T*
0.1046 Tw
(the electron-binding flavoproteins in the mitochon-)Tj
T*
0.0013 Tc
0.1236 Tw
[(drial respiratory chain with loss of ener)17.8(gy produc-)]TJ
T*
0.0194 Tc
0 Tw
(tion)Tj
6.6 0 0 6.6 326.636 79.2836 Tm
0 Tc
(4)Tj
11 0 0 11 330.0642 75.6536 Tm
0.0194 Tc
0.1056 Tw
(. The inhibition of mitochondrial respiration)Tj
ET
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51.99 707.96 487.56 -33.61 re
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BT
12 0 0 12 51.9863 699.7546 Tm
0 0 0 1 k
0 Tc
0 Tw
(Letter to the Editor)Tj
ET
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/GS1 gs
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0 Tw
(Tr)Tj
1.019 0 TD
-0.0001 Tc
[(eatment and pr)17.7(ophylaxis of ifosfamide-induced encephalopathy with)]TJ
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(intravenous methylene blue)Tj
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(may also lead to a disturbance of the intracellular)Tj
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0.0431 Tc
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T*
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T*
0.0236 Tc
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T*
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T*
0 Tc
0.0511 Tw
(extrahepatic tissues and in plasma by which chlora-)Tj
T*
0 Tw
(cetaldehyde can be formed)Tj
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(5)Tj
11 0 0 11 178.4114 608.6536 Tm
(. )Tj
-10.067 -1.1818 TD
0.006 Tc
0.119 Tw
(The experience in the management of this toxi-)Tj
-0.9767 -1.1818 TD
0 Tc
0.031 Tw
[(city is limited. Previous reports confirm that methy-)]TJ
T*
0.0891 Tw
(lene blue \(MB\) may be useful in the treatment and)Tj
T*
-0.0001 Tc
0.1078 Tw
(prophylaxis of IIE)Tj
6.6 0 0 6.6 139.9369 560.2836 Tm
0 Tc
(2-4, 6)Tj
11 0 0 11 156.045 556.6536 Tm
(. Several sites of action have)Tj
-9.0103 -1.1818 TD
-0.0001 Tc
0.0274 Tw
[(been proposed for MB: substitute for electron trans-)]TJ
T*
0.03 Tc
0.095 Tw
(port flavoprotein enzyme, restoration of hepatic)Tj
T*
0.0012 Tc
0.1238 Tw
(NADH oxidative function, and inhibition of extra-)Tj
T*
0.0105 Tc
0.1145 Tw
[(hepatic mono-amine oxidation of chlorethylamine)]TJ
T*
0 Tc
0 Tw
(to chloracetaldehyde)Tj
6.6 0 0 6.6 148.2425 495.2836 Tm
(7)Tj
11 0 0 11 151.5425 491.6536 Tm
(. )Tj
-7.6244 -1.1818 TD
-0.0798 Tc
(We)Tj
1.3078 0 TD
( )Tj
0.3082 0 TD
0 Tc
0.0582 Tw
(describe our experience of this potential neu-)Tj
-2.5927 -1.1818 TD
0.0985 Tw
(rological toxicity due to the possible fatal outcome)Tj
T*
0.0088 Tc
0.1162 Tw
(in some cases. In our patient, medications history)Tj
T*
0 Tc
0.055 Tw
[(was taken, and she was not taking others drugs that)]TJ
T*
0.0591 Tw
[(had possible interactions with IFOS. Brain involve-)]TJ
T*
0.024 Tw
(ment due to disease was ruled out. CNS toxicity oc-)Tj
T*
0.1072 Tw
(curred while the patient was receiving active treat-)Tj
T*
0.0863 Tw
[(ment with IFOS, and the symptoms exhibited were)]TJ
T*
0.0043 Tc
0.1206 Tw
(consistent with IIE. She benefited from using MB)Tj
T*
0 Tc
0.0875 Tw
(for acute treatment. When the patient was pre-trea-)Tj
T*
-0.0001 Tc
0.0865 Tw
(ted with MB before receiving further IFOS, the to-)Tj
T*
0 Tc
0.0034 Tw
(xicity was absent compared with the previous episo-)Tj
T*
-0.0001 Tc
0 Tw
(des. )Tj
0.9767 -1.1818 TD
0.0029 Tc
0.122 Tw
(As a conclusion, several recommendations must)Tj
-0.9767 -1.1818 TD
0 Tc
0.1244 Tw
(be done to prophylaxis and acute treatment of this)Tj
T*
-0.0001 Tc
0.1169 Tw
(syndrome. First, physicians prescribing ifosfamide,)Tj
T*
0.0076 Tc
0.1173 Tw
(especially in high doses, should monitor carefully)Tj
T*
0.0053 Tc
0.1196 Tw
(patients for early signs of toxicity in order to dis-)Tj
T*
0.0002 Tc
0.1248 Tw
(continue ifosfamide administration soon enough to)Tj
T*
0 Tc
0.0838 Tw
[(avoid development of mayor toxicity)64.9(. Second, high)]TJ
T*
0.1034 Tw
(risk patients should be considered to be those with)Tj
T*
0.0657 Tw
(creatinine levels of greater than 1.5 mg/dl or serum)Tj
T*
0.1243 Tw
(albumin levels of less than 3 g/dl or both, and the)Tj
T*
0.0342 Tc
0.0907 Tw
(risks and benefits of administration of the drug)Tj
T*
0 Tc
0.0561 Tw
[(should be judged accordingly)64.9(. Third, MB prophyla-)]TJ
T*
0.0502 Tw
(xis at dose of 50 mg iv diluted in 100 ml of normal)Tj
T*
0.0055 Tw
(saline in 10 minute infusion every six hours, may be)Tj
T*
0.0297 Tw
[(enable in previously af)17.8(fects patients to continue this)]TJ
T*
0.0104 Tc
0.1145 Tw
(treatment. Fourth, MB is the choice treatment for)Tj
T*
0 Tc
0.0668 Tw
[(IIE until resolution or a significant improvement of)]TJ
T*
0.0039 Tc
0.1211 Tw
[(symptoms is achived. MB administration does not)]TJ
T*
0.0101 Tc
0.1148 Tw
[(af)17.8(fect IFO pharmacocinetics. Thiamin \(100 mg at)]TJ
23.3349 56.7273 TD
0.0048 Tc
0.1201 Tw
(same schedule that MB\) may be reserved as a se-)Tj
0 -1.1818 TD
0 Tc
0.0271 Tw
[(cond therapeutic option in case a patient)54.9(s condition)]TJ
T*
0 Tw
(would not improve under MB)Tj
6.6 0 0 6.6 444.9808 677.2836 Tm
(8)Tj
11 0 0 11 448.2808 673.6536 Tm
(. )Tj
ET
Q
q
1 i
0 793 595 -793 re
0 793 m
W n
0.03 793.02 595.02 -793.02 re
W n
BT
/F2 1 Tf
11 0 0 11 341.4119 647.6536 Tm
0 0 0 1 k
/GS1 gs
-0.0001 Tc
0.0001 Tw
[(A. Snchez-Muoz, A. M. Gar)17.7(ca T)91.7(apiador)91.7(, )]TJ
1.7905 -1.1818 TD
[(E. Martnez Ortega, R. Dueas Gar)17.7(ca, )]TJ
-1.4004 -1.1818 TD
[(A. L. Ortega Granados, P)91.7(.)0( Snchez Rovira)]TJ
ET
Q
q
1 i
0 793 595 -793 re
0 793 m
W n
0.03 793.02 595.02 -793.02 re
W n
BT
/F1 1 Tf
11 0 0 11 410.4063 608.6536 Tm
0 0 0 1 k
/GS1 gs
0 Tc
0 Tw
(Servicio de Oncologa Mdica)Tj
-5.4814 -1.1818 TD
-0.0001 Tc
0.0001 Tw
[(Hospital Mdico Quirr)17.7(gico Ciudad de Jan)]TJ
12.0913 -1.1818 TD
0 Tw
(Jan \(Espaa\))Tj
ET
Q
q
1 i
0 793 595 -793 re
0 793 m
W n
0.03 793.02 595.02 -793.02 re
W n
BT
/F2 1 Tf
14 0 0 14 313.6146 530.6536 Tm
0 0 0 1 k
/GS1 gs
-0.0001 Tc
0 Tw
[(Refer)17.7(ences)]TJ
ET
Q
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1 i
0 793 595 -793 re
0 793 m
W n
0.03 793.02 595.02 -793.02 re
W n
BT
/F1 1 Tf
9 0 0 9 313.6146 506.9003 Tm
0 0 0 1 k
/GS1 gs
0 Tc
0.0804 Tw
[(1.)-683.8(Nicolao P and Giometto B. Neurological toxicity of ifosfa-)]TJ
1.4338 -1.1948 TD
0 Tw
(mide. Oncology 2003;65 \(suppl 2\):11-16.)Tj
-1.4338 -1.4338 TD
-0.0001 Tc
0.0989 Tw
[(2.)-683.9(Pelgrims J, De Vos F, Van den Brande J, et al. Methylene)]TJ
1.4338 -1.1948 TD
0 Tc
0.0922 Tw
(blue in the treatment and prevention of ifosfamide-induced)Tj
T*
0.0564 Tw
(encephalopathy: report of 12 cases and a review of the lite-)Tj
T*
-0.0001 Tc
0.0001 Tw
(rature. Br J Cancer 2000;82\(2\):291-294.)Tj
-1.4338 -1.4338 TD
0.0036 Tc
0.1213 Tw
[(3.)-680.2(Turner AR, Duong CD, Good DJ. Methylene blue for the)]TJ
1.4338 -1.1948 TD
0 Tc
0.0071 Tw
(treatment and prophylaxis of ifosfamide-induced encephalo-)Tj
T*
0 Tw
(pathy. Clinical Oncol 2003;15:435-439.)Tj
-1.4338 -1.4338 TD
0.0352 Tw
[(4.)-683.8(Kpfer A, Aeschlimann C, Wermuth B, Cerny T. Prophyla-)]TJ
1.4338 -1.1948 TD
0.0175 Tc
0.1075 Tw
(xis and reversal of encephalopathy with methylene-blue.)Tj
T*
0 Tc
0 Tw
(Lancet 1994; 343:763-764.)Tj
-1.4338 -1.4338 TD
0.0838 Tw
[(5.)-683.8(Aeschlimann C, Cerny T and Kpfer A. Inhibition of \(mo-)]TJ
1.4338 -1.1948 TD
0.0355 Tw
(no\) amine oxidase activity and prevention of ifosfamide en-)Tj
T*
0.075 Tc
0.0506 Tw
(cephalopathy by methylene blue. Drug Metab Disp)Tj
T*
0 Tc
0 Tw
(1996;24: 1336-1339.)Tj
-1.4338 -1.4338 TD
0.1054 Tw
[(6.)-683.8(Zulian GB, Tullen E, Maton B. Methylene blue for ifosfa-)]TJ
1.4338 -1.1948 TD
0.075 Tc
0.3381 Tw
(mide associated encephalopathy. N Engl J Med)Tj
T*
0 Tc
0 Tw
(1995;332:1239-1240.)Tj
-1.4338 -1.4338 TD
0.06 Tw
[(7.)-683.8(Donegan D. Novel treatment for the management of ifosfa-)]TJ
1.4338 -1.1948 TD
0.0192 Tw
(mide neurotoxicity: a rational for the use of methylene blue.)Tj
T*
0 Tw
(J Oncol Phar Pract 2001;6:153-165. )Tj
-1.4338 -1.4338 TD
0.0006 Tw
[(8.)-683.8(Buesa JM, Garca-Tejido P, Losa R, et al. Treatment of ifos-)]TJ
1.4338 -1.1948 TD
0.0423 Tw
(famide encephalopathy with intravenous thiamin. Clin Can-)Tj
T*
0 Tw
(cer Res 2003;9:4636-4637.)Tj
4.3014 -5.7351 TD
-0.0001 Tc
(Correspondence:)Tj
0 -1.1948 TD
(Dr. A. Snchez Muoz. )Tj
T*
0 Tc
(C/ Poeta Francisco Coronado y Delicado, 4 - 3 C)Tj
T*
-0.0001 Tc
(E-29011 Mlaga \(Spain\) )Tj
T*
0 Tc
(asmoncomed@yahoo.es)Tj
ET
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56.93 736.31 m
544.49 736.31 l
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0 793 m
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W n
BT
/F2 1 Tf
10 0 0 10 409.5196 750.1821 Tm
0 0 0 1 k
/GS1 gs
0 Tc
0 Tw
(Oncologa, 2006; 29 \(3\):140-141)Tj
ET
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520.48 55.99 24.01 -17.01 re
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