Contribution to the treatment of nausea and emesis induced by chemotherapy in children and adolescents with osteosarcoma.

CONTEXT AND OBJECTIVE: Chemotherapy-induced emesis is a limiting factor in treating children with malignancies. Intensive chemotherapy regimens along with emetogenic drug administration have increased the frequency and severity of emesis and nausea. Our study was designed to consider the importance of this problem and the need for improvement in emesis treatment for patients receiving chemotherapy. Our objective was to compare the efficacy and safety of the antiemetic drug granisetron and a regimen of metoclopramide plus dimenhydrinate. DESIGN AND SETTING: Open, prospective and randomized study at Instituto de Oncologia Pediátrica, Department of Pediatrics, Universidade Federal de São Paulo. METHODS: From February to August 1994, 26 patients (mean age: 14 years) with osteosarcoma received 80 chemotherapy cycles of iphosphamide (2,500 mg/m2) plus epirubicin (75 mg/m2) or carboplatin (600 mg/m2), or epirubicin (75 mg/m2) plus carboplatin (600 mg/m2). Eighty chemotherapy treatments were analyzed regarding nausea and vomiting control. Patients were randomized to receive either a single dose of granisetron (50 microg/kg) or metoclopramide (2 mg/kg) plus dimenhydrinate (5 mg/kg infused over eight hours). Emesis and nausea were monitored for 24 hours by means of the modified Morrow Assessment of Nausea and Emesis. Statistical analysis utilized the chi-squared, Student t and Mann-Whitney tests, plus data exploration techniques. RESULTS: 62.5% of the patients undergoing chemotherapy responded completely to granisetron, whereas 10% responded to metoclopramide plus dimenhydrinate (p < 0.0001). No severe adverse reactions were found in either of the treatments given. CONCLUSION: In children and adolescents with osteosarcoma, granisetron was safe and more efficient than metoclopramide plus dimenhydrinate for controlling chemotherapy-induced emesis and nausea.

Contribution to the treatment of nausea and emesis induced by chemotherapy in children and adolescents with osteosarcoma

CONTEXTO E OBJETIVO: A êmese induzida por quimioterapia é fator limitante no tratamento de crianças com câncer. O uso de quimioterapia com drogas emetogênicas tem aumentado a freqüência desse efeito colateral. O objetivo é comparar a eficácia e a toxicidade do granisetron às da combinação de altas doses de metoclopramida e dimenidrato em crianças com osteossarcoma utilizando a mesma quimioterapia. TIPO DE ESTUDO E LOCAL: Aberto, prospectivo, randomizado, realizado no Instituto de Oncologia Pediátrica, Departamento de Pediatria, Universidade Federal de São Paulo, Brasil. MÉTODOS: Entre fevereiro e agosto de 1994, 26 crianças com idade de 7 a 18 anos (média de 14 anos), recebendo quimioterapia para osteossarcoma, entraram no estudo. A quimioterapia consistiu de ciclos repetidos de: A) ifosfamida 2.500 mg/m² + epirrubicina 75 mg/m²; B) ifosfamida 2.500 mg/m² + carboplatina 600 mg/m²; C) carboplatina 600 mg/m² + epirrubicina 75 mg/m². 80 tratamentos quimioterápicos foram avaliados para o controle de náuse e vômito. Os pacientes foram randomizados para receber dose única de granisetron (50 µ/kg) ou metoclopramida (2 mg/kg) mais dimenidrato (5 mg/kg) infundidos por oito horas. Êmese e náusea foram monitoradas por 24 horas por meio de escore de MANE (Morrow Assessment of Nausea and Emesis). Foram utilizados testes de Qui-quadrado, t e Mann Whitney, além da técnica de análise exploratória de dados. RESULTADOS: O granisetron induziu resposta completa em 62,5% dos pacientes submetidos aos tratamentos quimioterápicos comparado a apenas 10% obtidos com a combinação de metoclopramida associado ao dimenidrato (p < 0,0001). CONCLUSÕES: Concluímos que o granisetron é droga segura e eficiente em crianças com osteossarcoma superior à associação de metoclopramida e dimenidrato no controle de náuseas e vômitos induzidos por quimioterapia para osteossarcoma em crianças.

Cardioprotective effect of dexrazoxane during treatment with doxorubicin: a study using low-dose dobutamine stress echocardiography.

AIM: To assess the late cardioprotective effect of dexrazoxane associated with doxorubicin during treatment of osteosarcoma by means of low-dose dobutamine stress echocardiography (LDDSE) in non-relapsed asymptomatic children and teenagers. PATIENTS AND METHODS: The study population included 58 patients with osteosarcoma divided in three groups, with equivalent age range, gender proportion and body surface area. Group I (21 patients, 14 males, 15 +/- 4 years) was analyzed before chemotherapy and considered the control group; Group II (19 patients, 11 males, 19.7 +/- 4 years) was treated with 348.4 +/- 18 mg/m2 of doxorubicin only and Group III (18 patients, 14 male, 16.8 +/- 5 years) treated with 396.5 +/- 55 mg/m2 of doxorubicin with dexrazoxane in the ratio 10:1. The patients were submitted to LDDSE (maximal dose 5 microg/kg/min). No major side effects were observed. Heart rate, blood pressure, left ventricular diameters, end systolic wall stress (ESWS), and other diastolic and systolic function indexes were assessed at rest conditions and during LDDSE and compared between the three groups. RESULTS: Group III received a doxorubicin dose significantly greater than Group II (P = 0.001). During LDDSE there were no significant changes in the diastolic function indexes in any of the groups, but there was a significant increase of systolic indexes and a decrease of ESWS in Group III compared to group II. There was no significant difference of any systolic functional parameters between Group I and III. Considering the ejection fraction (EF) at rest or at LDDSE, 13 patients (69.4%) in Group II and 5 patients (27.7%) in Group III were considered to have systolic dysfunction. (P = 0.02). CONCLUSION: Myocardial response to LDDSE in patients treated with doxorubicin and dexrazoxane was similar to patients without chemotherapy and better than those treated with doxorubicin only, suggesting less cardiotoxicity.

Use of amifostine in the therapy of osteosarcoma in children and adolescents.

Amifostine protects normal tissue from the cytotoxic damage induced by radiation and chemotherapy. In this study, 39 consecutive newly diagnosed children with osteosarcoma were assessed; 20 received amifostine and 19 did not. The chemotherapy regimen included an induction phase of three cycles of cisplatin (100 mg/m2), carboplatin (500 mg/m2), and doxorubicin (60 mg/m2), followed by surgery. Alternating cycles of cisplatin/ifosfamide (9 mg/m2), ifosfamide/doxorubicin, carboplatin/doxorubicin, and ifosfamide/carboplatin were administered every 3 weeks to complete 26 weeks of treatment. Amifostine was administered 15 minutes before the infusions of cisplatin and carboplatin in a total of 193 infusions. Side effects during infusions and renal, hearing, and bone marrow toxicities were evaluated and compared between the two groups. Hypotension was observed in 28 (14.5%) infusions. No patient required discontinuation of therapy. Fewer than two episodes of vomiting occurred in 130 (71%) infusions and two to five episodes occurred in 51 (28%) infusions, and no patient had grade 4 toxicity. There was no difference between the two groups regarding renal toxicity (creatinine clearance). Neutropenia and leukopenia were significantly less frequent in the amifostine group. No difference was observed in platelet and hearing toxicities. Amifostine was well tolerated in doses of 740 mg/m2 in children and adolescents, and myelotoxicity was less severe in the amifostine group. This was a pilot study for further evaluation in a larger randomized trial.