Protective effect of dexrazoxane on cardiotoxicity in breast cancer patients who received anthracycline-containing chemotherapy / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the cardioprotective effects of dexrazoxane (DEX) on breast cancer patients who received anthracycline-containing chemotherapy.</p><p><b>METHODS</b>A total of 122 breast cancer patients after operation were randomly divided into two groups: The experimental group of 61 cases treated with EPI plus DEX (DEX:EPI = 10:1) as adjuvant chemotherapy regimen, and the control group of 61 cases treated with EPI but without DEX. All patients received four cycles of adjuvant chemotherapy and their changes of specific cardiac functional status and hematology status before and after chemotherapy, as well as non-cardiac toxicity were observed and analyzed.</p><p><b>RESULTS</b>Brain natriuretic peptide (BNP) before chemotherapy and after four cycles of chemotherapy in the control group was (106.78 ± 4.52)×10(-6) µg/ml and (187.19 ± 8.71)×10(-6) µg/ml, respectively, with a significant difference between them (P < 0.05). It in the experimental group was (102.34 ± 8.76)×10(-6) µg/ml and (105.29 ± 7.21)×10(-6) µg/ml, respectively, without a significant difference (P > 0.05). Cardiac troponin T (cTnT) before chemotherapy and after four cycles of chemotherapy in the control group was (12.55 ± 2.73)×10(-3) µg/ml and ( 31.05 ± 7.10 )×10(-3) µg/ml, respectively, with a significant difference between them (P < 0.05). It in the experimental group was (12.70 ± 2.15)×10(-3) µg/ml and (13.65 ± 7.82)×10(-3) µg/ml, respectively, without a significant difference (P > 0.05). The hart rate (HR) before chemotherapy and after four cycles of chemotherapy in the control group, was 75.32 ± 7.14 bpm and 89.60 ± 9.21 bpm, respectively, with a significant difference (P < 0.05). It in the experimental group was 78.60 ± 6.29 bpm and 83.10 ± 7.56 bpm, respectively, without a significant difference (P > 0.05). The left ventricular ejection fraction (LVEF) before chemotherapy and after four cycles of chemotherapy in the control group was (65.23 ± 7.82)% and (55.21 ± 7.23)%, respectively, with a significant difference between them (P < 0.05). It in the experimental group was (64.12 ± 6.25)% and (59.6 ± 4.72)%, respectively, without a significant difference (P > 0.05). The absolute neutrophil count before chemotherapy and after four cycles of chemotherapy in the control group was (3.95 ± 1.36)×10(9)/L and (3.50 ± 1.52)×10(9)/L, respectively, without a significant difference (P > 0.05). It in the experimental group, was (4.96 ± 1.41)×10(9)/L and (3.10 ± 1.26)×10(9)/L, respectively, with a significant difference (P < 0.05). The incidence of grade I-IV bone marrow suppression in the experimental group was 21.3%, 16.4%, 24.6%, and 4.9%, respectively. It in the control group was 16.4%, 11.5%, 9.8%, and 5.5%, respectively, with a significant difference (P < 0.05).</p><p><b>CONCLUSIONS</b>Cardiac toxicity after anthracycline treatment in breast cancer patients may be significantly reduced by DEX, without increase of non-cardiac and and non-hematologic toxicity. DEX combined with anthracycline increases the risk of bone marrow suppression, therefore, peripheral blood picture should be monitored or routine bone marrow support may be needed.</p>

Dexrazoxane for Preventing Anthracycline Cardiotoxicity in Children with Solid Tumors

This study attempted to assess the incidence and outcome of anthracycline cardiotoxicity and the role of dexrazoxane as a cardioprotectant in childhood solid tumors. The dexrazoxane group included 47 patients and the control group of historical cohort included 42. Dexrazoxane was given in the 10:1 ratio to doxorubicin. Fractional shortening and systolic and diastolic left ventricular diameters were used to assess the cardiac function. The median follow-ups were 54 months in the dexrazoxane group and 86 months in the control group. The mean cumulative doses of doxorubicin were 280.8+/-83.4 mg/m2 in the dexrazoxane group and 266.1+/-75.0 mg/m2 in the control group. The dexrazoxane group experienced significantly fewer cardiac events (27.7% vs. 52.4%) and less severe congestive heart failure (6.4% vs. 14.3%) than the control group. Thirteen cardiotoxicities including one cardiac death and 2 congestive heart failures occurred in the dexrazoxane group, and 22 cardiotoxicities including 2 cardiac deaths and 4 congestive heart failures, in the control group. Five year cardiac event free survival rates were 69.2% in the dexrazoxane group and 45.8% in the control group (P=0.04). Dexrazoxane reduces the incidence and severity of early and late anthracycline cardiotoxicity in childhood solid tumors.

Função sistólica do ventrículo esquerdo pela ecocardiografia em crianças e adolescentes com osteossarcoma tratados com doxorrubicina com e sem dexrazoxane / Left ventricular systolic function assessed by echocardiography in children and adolescents with osteosarcoma treated with doxorubicin alone or in combination with dexrazoxane

OBJETIVO: Avaliar o comportamento da função sistólica do ventrículo esquerdo (VE) pela ecocardiografia em pacientes com osteossarcoma tratados com doxorrubicina com e sem dexrazoxane. MÉTODOS: Foram estudados 55 pacientes com osteossarcoma com ou sem metástase submetidos à quimioterapia (QT) com seis ciclos de doxorrubicina, divididos em dois grupos, conforme o uso de dexrazoxane. Grupo I: 37 pacientes, os quais receberam dexrazoxane (28 do sexo masculino, com média de idade de 15,4 anos). Grupo II: 18 pacientes, que não receberam dexrazoxane (15 do sexo masculino, com média de idade de 15,1 anos). Foram realizadas quatro avaliações ecocardiográficas: 1) antes do início da QT (avaliação inicial); 2) até duas semanas após o terceiro ciclo; 3) até duas semanas após o quinto ciclo e 4) até quatro semanas após o sexto ciclo da QT (avaliação final). A função sistólica do VE foi avaliada pela porcentagem de encurtamento (PE) com o ecocardiograma. Alteração da função contrátil ou toxicidade miocárdica foi definida com valores de PE iguais ou inferiores a 29 por cento e/ou diminuição da PE, em valor absoluto, igual ou superior a 10 unidades do valor inicial de cada paciente. RESULTADOS: Não houve diferença significativa entre os grupos quanto à idade, sexo e raça. A dose cumulativa de doxorrubicina foi significantemente maior no grupo II em todas as fases do tratamento: 174 x 203 mg/m²; 292 x 338 mg/m² e 345 x 405 mg/² (p < 0,0001). A ocorrência de disfunção sistólica do VE, de acordo com os critérios previamente definidos, foi de sete indivíduos no grupo I (18,92 por cento) e de dois no grupo II (11,1 por cento), diferença não significativa (p=0,248). A análise de variância com medidas repetidas não mostrou diferença significativa nas médias da PE ao longo do período de estudo (p=0,967). Entretanto foi encontrada diferença significativa (p=0,029) entre as médias da PE dos grupos I e II nas avaliações 2 (35,67 x 37,21 por cento), 3 (34,95 x 38,47 por cento) e 4...

OBJECTIVE: To evaluate left ventricular (LV) systolic function by means of echocardiography in patients with osteosarcoma treated with doxorubicin alone or in combination with dexrazoxane. METHODS: The study analyzed 55 patients with osteosarcoma, with or without metastasis, undergoing a six-cycle chemotherapy regimen of doxorubicin, who were divided into two groups according to dexrazoxane use. Group I: Thirty-seven patients who did not receive dexrazoxane (28 males, average age 15.4 years). Group II: Eighteen patients who did receive dexrazoxane (15 males, average age 15.1 years). Four echocardiographic evaluations were performed: 1) before the beginning of the chemotherapy (initial evaluation); 2) up to two weeks after the third cycle; 3) up to two weeks after the fifth cycle; and 4) up to four weeks after the sixth cycle of chemotherapy (final evaluation). The left ventricular systolic function was assessed by the fractional percentage of systolic shortening (FS percent) on echocardiography. Alterations in the contractile function or cardiac toxicity were defined as FS percent values equal to or lower than 29 percent, and/or by a drop in FS percent by an absolute value equal to or greater than 10 units of the baseline value of each patient. RESULTS: No significant difference as to age, gender, and race was observed between the groups. The cumulative dose of doxorubicin was significantly higher in group II throughout all phases of the treatment: 174 x 203 mg/m²; 292 x 338 mg/m² and 345 x 405 mg/² (p < 0.0001). According to previously established criteria, the incidence of LV systolic dysfunction was not significantly different (p=0.248) between patients in group I (18.92 percent) and patients in group II (11.1 percent). The variance analysis with repeated measurements did not show significant differences in the means of fractional percentage of systolic percentage (FS percent) throughout the study (p=0.967). However, a significant difference (p=0.029) was...

Terapêutica citoprotetora em pacientes tratados com químio e/ou radioterapia anti neoplásica / Cytoprotective therapy in patients treated with chemotherapy and/or antineoplasic radiotherapy

Nos últimos anos, vários agentes citoprotetores têm sido desenvolvidos para proteger células normais dos efeitos tóxicos da quimioterapia e radioterapia. O agente citoprotetor ideal seria aquele capaz de permitir a intensificaçäo da dose dos quimioterápicos; proteger um amplo espectro de órgäos e tecidos quando do tratamento com diversos fármacos quimioterápicos; conferir proteçäo específica aos tecidos normais; preservar o efeito anti-tumoral e ter pequena e/ou controlável toxicidade e efeitos colaterais. Um citoprotetor deve ser administrado antes da quimioterapia citotóxica, ao contrário dos fatores estimuladores de colônia e do Leucovorin, que säo administrados após quimioterapia como resgate à medula óssea e estimular a sua recuperaçäo. Do ponto de vista prático existem três agentes citoprotetores: dois citoprotetores quimio-específicos (Dexrazoxane e Mesna) e um citoprotetor de amplo espectro (Amifostina). Os autores discutem as principais propriedades e utilidades destas drogas utilizadas em Onco Hematologia.

Current role of chemotherapy protectors in cancer treatment

The administration of full doses of chemotherapy according to an established schedule improves the response rate and duration of response in cancer patients. However, frequently there are delays in therapy due to dose-limiting side effects and chemotherapy could affect permanently normal tissues. This has led to the development of chemotherapy protectors and of rescue agents in the past years. We will discuss some of these new agents and their use in cancer treatment. Some of these agents include amifostine (Ethyol), dexrazoxane (Zinecard), mesna (Mesnex), leucovorin, G-CSF, GM CSF, recombinant erythropoietin and thrombopoietin. Oncologists must learn the adequate use of different strategies in reducing chemotherapy toxicity in order to improve both the quality and quantity of life of cancer patients

Razoxane y teleroentgen radiación en psoriasis resistentes al PUVA y al metotrexato / Razoxane and teleroentgentherapy in psoriasis resistent to PUVA and methotrexate

Se describe la experiencia clínica con el uso de Razoxone ICRF 159, una nueva droga antitumoral, en el tratamiento de 57 pacientes con formas severas de psoriasis. Esta medicación demostró ser efectiva sobre todo en las formas generalizadas eritrodérmicas y con compromisos articulares. Es bien tolerada y parece estar libre de hepatotoxicidad; sin embargo puede producir depresión medular, efecto que está directamente relacionado con la dosis. Se investigó su asociación con teleroentgenterapia por su propiedad radiopotenciadora