Palonosetron versus granisetron in combination with aprepitant for the prevention of chemotherapy-induced nausea and vomiting in patients with gynecologic cancer / 부인종양

OBJECTIVE: There is no research regarding the appropriate antiemetic agents for female patients, especially those receiving moderately emetogenic chemotherapy (MEC). We evaluated the antiemetic efficacy of a combination of 5-HT3 receptor with/without aprepitant in patients with gynecological cancer treated with the TC (paclitaxel and carboplatin) regimen of MEC. METHODS: We enrolled 38 patients diagnosed with gynecologic cancer and scheduled to receive the TC regimen. The patients were randomly assigned to receive a 5-HT3 receptor antagonist, either palonosetron in the first cycle followed by granisetron in the second cycle or vice versa. In the third cycle, all patients received a combination of the 5-HT3 receptor and dexamethasone with/without aprepitant. RESULTS: When three drugs were administered, palonosetron consistently produced an equivalent complete response (CR) rate to granisetron in the acute phase (89.5% vs. 86.8%, p=0.87) and delayed phase (60.5% vs. 65.8%, p=0.79). With regard to the change in dietary intake, palonosetron exhibited similar efficacy to granisetron in the acute phase (92.1% vs. 89.4%, p=0.19) and delayed phase (65.7% vs. 68.4%, p=0.14). However, in the delayed phase, the addition of aprepitant therapy with a 5-HT3 receptor antagonist and dexamethasone produced a higher CR rate than a 5-HT3 receptor antagonist with dexamethasone (93.3% vs. 47.8%, p<0.001) and allowed the patients to maintain a higher level of dietary intake (93.3% vs. 56.5%, p<0.001). CONCLUSION: The addition of aprepitant therapy was more effective than the control therapy of a 5-HT3 receptor antagonist, and dexamethasone in gynecological cancer patients treated with the TC regimen.

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.

The efficacy of granisetron for cancer patients undergoing platinum-based chemotherapy: comparison of 1 miligram versus 3 miligram doses in preventing nausea and vomiting.

AIM: To compare the efficacy of anti-emetic and prophylactic effects of 1 milligram (mg) versus 3 mg granisetron in cancer patients. METHODS: In this double blind, randomized, parallel study, 2-dose regimens of intra venous (IV) granisetron were evaluated in 39 cancer patients who were treated with platinum-based chemotherapy. Patients who met the inclusion criteria were randomized to receive granisetron 1 mg IV plus dexamethasone 20 mg (group A) or granisetron 3 mg iv plus dexamethasone 20 mg (group B). A questionnaire was used to evaluate the anti-emetic effects of granisetron. RESULTS: Subjects consisted of 31 men and 8 women. In group A (19 patients) 57.9% showed complete response from vomiting, 10.5% of major response, and 31.6% of failure to anti-emetic therapy. There were 47.4% of patients free from nausea and 52.6% complained of nausea (mild, moderate, and severe nausea). Among group B (20 patients), 90% showed complete response from vomiting, 5% of major response, and 5% of failure to anti-emetic therapy. Eighty percent of patients were free from nausea, while 15% complained of mild nausea and 5% of moderate nausea. The differences were statistically significant for vomiting (p = 0.02) as well as for nausea (p = 0.03). CONCLUSION: Intravenous granisetron 3 mg has better efficacy than granisetron 1 mg in preventing cisplatin- induced acute emesis.

Comparative study of low-dose oral granisetron plus dexamethasone and high-dose metoclopramide plus dexamethasone in prevention of nausea and vomiting induced by CHOP-therapy in young patients with non-Hodgkin's lymphoma.

Standard-dose (2 mg/day) oral granisetron seems to have more antiemetic efficacy than that of high-dose (0.5-1 mg/kg/dose) metoclopramide in moderately emetogenic chemotherapy. However, the cost of oral granisetron is much higher than that of metoclopramide so the authors tried to overcome this disadvantage by dose reduction and adding dexamethasone to enhance the antiemetic effect of oral granisetron. Twenty four young patients (aged < 50 years), with non-Hodgkin's lymphoma receiving CHOP-therapy were enrolled and evaluated in a randomized, double-blind, crossover study comparing the antiemetic efficacy, toxicity and patients' preference of a combination of low-dose oral granisetron plus intravenous dexamethasone (gran/dex) with a combination of high-dose metoclopramide plus intravenous dexamethasone (met/dex) on days 1-5 after chemotherapy. The acute, delayed (day 2-5) and 5-day total control of nausea and vomiting in the gran/dex group were significantly higher than those of the met/dex group (75.0% vs 25.0%; p-value = 0.004, 79.2% vs 33.3%; p-value = 0.007 and 75.0% vs 25.0%; p-value = 0.004, respectively). Except for extrapyramidal reactions in the met/dex group, the side effects in both groups were comparable. The mean total score of antiemetic preference in the gran/dex group was also significantly higher than that of the met/dex group (9.0 vs 7.5; p-value = 0.004). In conclusion, low-dose oral granisetron combined with intravenous dexamethasone had significantly higher protective effects against both acute and delayed nausea and vomiting induced by CHOP-therapy. Thus, this regimen may be considered as an alternative outpatient antiemetic treatment for young patients with non-Hodgkin's lymphoma.

Novos avanços no controle da náusea pós-quimioterapia antineoplásica / New advances in controlling nausea and vomiting related to anticancer chemotherapy

A náusea é um dos efeitos colaterais mais temidos pelos pacientes que se submetem à quimioterapia (QT) antineoplásica. O controle inadequado desta complicaçäo confere significativa morbidade aos pacientes tratados com QT. Com o advento dos antagonistas dos receptores 5-HT, a incidência de náusea e vômito relacionados à quimioterapia (NVQT) diminuiu significativamente. Isso permitiu a administraçäo de regimes altamente emetizantes em nível ambulatorial para a maioria dos pacientes com câncer, melhorando sua qualidade de vida. O uso dessas drogas, entretanto, aumentou sobremaneira os custos do tratamento. Nesta revisäo, abordaremos sumariamente os mecanismos fisiopatológicos da emese, para entäo podermos compreender como atuam as drogas antieméticas atualmente utilizadas na prática oncológica. Discutiremos também os novos rumos da pesquisa clínica nesta área, incluindo estratégias para minimizar o custo desse tratamento