RESUMEN
BACKGROUND: The localization of substance P in brain-stem regions associated with vomiting, and the results of studies in ferrets, led us to postulate that a neurokinin-1-receptor antagonist would be an antiemetic in patients receiving anticancer chemotherapy. METHODS: In a multicenter, double-blind, placebo-controlled trial involving 159 patients who had not previously received cisplatin, we evaluated the prevention of acute emesis (occurring within 24 hours) and delayed emesis (on days 2 to 5) after a single dose of cisplatin therapy (70 mg or more per square meter of body-surface area). Before receiving cisplatin, all the patients received granisetron (10 microg per kilogram of body weight intravenously) and dexamethasone (20 mg orally). The patients were randomly assigned to one of three treatments in addition to granisetron and dexamethasone: 400 mg of an oral trisubstituted morpholine acetal (also known as L-754,030) before cisplatin and 300 mg on days 2 to 5 (group 1), 400 mg of L-754,030 before cisplatin and placebo on days 2 to 5 (group 2), or placebo before cisplatin and placebo on days 2 to 5 (group 3). Additional medication was available at any time to treat occurrences of vomiting or nausea. RESULTS: In the acute-emesis phase, 93 percent of the patients in groups 1 and 2 combined and 67 percent of those in group 3 had no vomiting (P<0.001). In the delayed-emesis phase, 82 percent of the patients in group 1, 78 percent of those in group 2, and 33 percent of those in group 3 had no vomiting (P<0.001 for the comparison between group 1 or 2 and group 3). The median nausea score in the delayed-emesis phase was significantly lower in group 1 than in group 3 (P=0.003). No serious adverse events were attributed to L-754,030. CONCLUSIONS: The neurokinin-1-receptor antagonist L-754,030 prevents delayed emesis after treatment with cisplatin. Moreover, combining L-754,030 with granisetron plus dexamethasone improves the prevention of acute emesis.
Asunto(s)
Acetales/uso terapéutico , Antieméticos/uso terapéutico , Cisplatino/efectos adversos , Morfolinas/uso terapéutico , Antagonistas del Receptor de Neuroquinina-1 , Vómitos/prevención & control , Acetales/efectos adversos , Anciano , Antieméticos/efectos adversos , Aprepitant , Dexametasona/uso terapéutico , Método Doble Ciego , Quimioterapia Combinada , Femenino , Granisetrón/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Morfolinas/efectos adversos , Satisfacción del Paciente , Antagonistas de la Serotonina/uso terapéutico , Vómitos/inducido químicamenteRESUMEN
Dolasetron mesilate is a selective 5-HT3 receptor antagonist that prevents chemotherapy-induced and postoperative nausea and vomiting. For the majority of patients in intravenous dolasetron trials for chemotherapy-induced nausea and vomiting, dosing has been based on body weight (mg/kg). The approved weight-based dose is 1.8 mg/kg based on results of controlled clinical trials. However, trials of dolasetron evaluating oral doses for prevention of chemotherapy-induced emesis, and intravenous doses for prevention and treatment of postoperative emesis have used a fixed milligram dose. To identify an appropriate intravenous fixed milligram dose for the prevention of chemotherapy-induced nausea and vomiting, this analysis was performed to derive efficacy results for fixed milligram doses from pooled results obtained with dosing based on body weight. Intravenous dolasetron doses for 1,598 patients treated on a mg/kg basis (0.3, 0.6, 1.2, 1.8, 2.4, 3.0 and 5.0 mg/kg) in 14 clinical trials were converted to fixed milligram doses based on weight. Fixed-dose groups were established at doses of 50, 75, 100, 125, 150, and 200 mg. Doses less than or equal to the midpoint between two dose groups were included in the lower dose group. Pooled results showed that the 100 mg intravenous dolasetron dose group (who received actual doses of 88-112 mg) produced the highest rate (53%) of complete response (0 emetic episodes and no rescue medication in the 24-h period following initiation of chemotherapy).
Asunto(s)
Antieméticos/administración & dosificación , Antineoplásicos/efectos adversos , Cisplatino/efectos adversos , Indoles/administración & dosificación , Náusea/prevención & control , Quinolizinas/administración & dosificación , Vómitos/prevención & control , Adolescente , Adulto , Anciano , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Humanos , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Náusea/inducido químicamente , Neoplasias/tratamiento farmacológico , Vómitos/inducido químicamenteRESUMEN
PURPOSE: Dolasetron is a 5-HT3 antagonist antiemetic with active oral and intravenous formulations. The effects of this class are enhanced when combined with dexamethasone. This study tested the ability of the combination of oral dolasetron 200 mg and oral dexamethasone 20 mg to prevent acute emesis in cancer patients receiving initial cisplatin at doses > or = 70 mg/m2. Additionally, patients were randomly assigned to receive a second dosage of the regimen 16 hours later to improve control of acute symptoms. PATIENTS AND METHODS: A total of 75 patients were entered, with 38 randomized to the two-dose regimen. Thirty-five percent were women and 77% had lung cancer. RESULTS: Overall, the regimen prevented acute vomiting in 76% (95% confidence interval, 65% to 85%), including 74% of 35 patients who received cisplatin at doses > or = 100 mg/m2. There was no observed difference in emesis prevention between the one-dose (76%) and two-dose (76%) regimens (95% confidence interval for the difference, -20% to 19%). The median time to the onset of emesis was 19 hours for the one-dose regimen and 17 hours for the two-dose regimen in those patients with emesis. Headache occurred in 11% who received one dose and 16% who received two doses. CONCLUSION: The combination of oral dolasetron 200 mg and dexamethasone 20 mg given only once prevented acute emesis in 76% of patients who received cisplatin > or = 70 mg/m2. Administration of a second dose of the regimen did not improve the observed prevention rate or delay the time to emesis. This one-dose oral regimen has comparable or better effectiveness than reported results of intravenous combination regimens in preventing cisplatin-induced vomiting and merits further study and use.
Asunto(s)
Antieméticos/uso terapéutico , Antineoplásicos/efectos adversos , Cisplatino/efectos adversos , Dexametasona/uso terapéutico , Indoles/uso terapéutico , Quinolizinas/uso terapéutico , Vómitos/prevención & control , Enfermedad Aguda , Administración Oral , Antieméticos/administración & dosificación , Antineoplásicos/administración & dosificación , Cisplatino/administración & dosificación , Dexametasona/administración & dosificación , Quimioterapia Combinada , Femenino , Humanos , Indoles/administración & dosificación , Masculino , Persona de Mediana Edad , Náusea/inducido químicamente , Náusea/prevención & control , Neoplasias/tratamiento farmacológico , Quinolizinas/administración & dosificación , Vómitos/inducido químicamenteRESUMEN
BACKGROUND: This double blind parallel group study assessed the acute antiemetic efficacy of four oral doses of dolasetron mesylate in cancer patients receiving their first course of intravenous chemotherapy with doxorubicin and/or cyclophosphamide. METHODS: Patients were randomized to receive 25, 50, 100, or 200 mg of dolasetron mesylate 30 minutes prior to chemotherapy and were monitored for nausea and emetic episodes for the next 24 hours. RESULTS: Three hundred and nineteen cancer patients at 32 sites completed the study. Most patients were female (81%); of this group, 69% had breast carcinoma. A highly statistically significant linear trend demonstrating improved response with higher doses was detected for complete response (no emetic episodes and no rescue medication) (P < 0.001), for complete plus major response (0-2 emetic episodes and no rescue medication) (P < 0.001), and for patient visual analog scale assessments of nausea (P = 0.001) and general satisfaction with antiemetic therapy (P = 0.001). No serious adverse events were noted. The most frequent adverse event was mild, self-limiting headache, which has been reported with other drugs in this class. CONCLUSIONS: Single oral doses of dolasetron mesylate were found to be effective in preventing acute emesis in cancer patients receiving moderately emetogenic chemotherapy.
Asunto(s)
Antieméticos/administración & dosificación , Antineoplásicos/efectos adversos , Indoles/administración & dosificación , Náusea/prevención & control , Quinolizinas/administración & dosificación , Administración Oral , Antieméticos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ciclofosfamida/efectos adversos , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Doxorrubicina/efectos adversos , Femenino , Humanos , Indoles/efectos adversos , Masculino , Persona de Mediana Edad , Náusea/inducido químicamente , Quinolizinas/efectos adversosRESUMEN
PURPOSE: This double-blind, dose-response study was conducted to assess the safety and efficacy of four oral doses of dolasetron mesylate for preventing acute emesis in cancer patients receiving their first course of moderately emetogenic platinum-containing chemotherapy. PATIENTS AND METHODS: Patients were randomized to receive a single oral dose of 25, 50, 100, or 200 mg dolasetron 30 minutes before receiving IV carboplatin (275-400 mg/m2)- or cisplatin (20-50 mg/m2)-containing chemotherapy, then monitored for nausea and vomiting for 24 hours. RESULTS: Three hundred seven cancer patients from 32 sites completed the study. There was a statistically significant dose response across the four doses for complete response (no emetic episodes or rescue medication): 44.7%, 71.3%, 73.2%, and 82.5% for the 25, 50, 100, or 200 mg doses of dolasetron, respectively. Patients' nausea severity and patient satisfaction visual analogue scale scores also showed a statistically significant trend with dose. All doses of dolasetron were well tolerated. The most common adverse events were headache (17.6%) and dizziness (2.0%). DISCUSSION: This study demonstrates the safety and antiemetic efficacy of oral dolasetron mesylate in patients receiving moderately emetogenic platinum-containing chemotherapy with the highest antiemetic activity observed at 200 mg.
Asunto(s)
Antieméticos/uso terapéutico , Indoles/uso terapéutico , Quinolizinas/uso terapéutico , Vómitos/prevención & control , Administración Oral , Anciano , Antineoplásicos/administración & dosificación , Carboplatino/administración & dosificación , Cisplatino/administración & dosificación , Demografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Vómitos/inducido químicamenteRESUMEN
Thirty-two patients with metastatic carcinoma of the prostate refractory to endocrine therapy were entered on trial. No patient entered in the study had prior chemotherapy. Patients were treated with 5-fluorouracil given at a dosage of 4 gm/m2 over a 24-hour period every 2 weeks. Of the 27 patients evaluable for response, there were no complete or partial remissions, but 9 (33%) had a stable disease. The 95% confidence interval for complete and partial response in this series (0 of 27 patients) is 0.0-12%. Myelosuppression and gastrointestinal toxicity was moderate. Two patients, however, experienced major but completely reversible neurotoxicity, including 1 with cerebellar ataxia and 1 with memory loss and stroke-like symptoms. These data indicate that high-dose fluorouracil used in this dosage and schedule is ineffective in the therapy of advanced carcinoma of the prostate.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Fluorouracilo/administración & dosificación , Neoplasias de la Próstata/tratamiento farmacológico , Adenocarcinoma/secundario , Adulto , Anciano , Anciano de 80 o más Años , Evaluación de Medicamentos , Fluorouracilo/efectos adversos , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/patología , Análisis de SupervivenciaRESUMEN
Twenty patients with primary non-Hodgkin's lymphoma of the central nervous system (CNS) were seen at Vanderbilt and its affiliated hospitals between 1974 and 1986. Histologically, the most common subtypes were large, noncleaved cell lymphoma and immunoblastic lymphoma of B cells. However, multiple histologies were identified. Lesions most commonly involved the frontal lobes and/or deep nuclei. Positive cerebrospinal fluid cytology was rare at initial presentation. Seventeen patients were treated with surgical biopsy or resection followed by whole brain radiotherapy at a median dose of 5,000 cGy (range: 3,000-5,600 cGy). Seven patients have been followed for less than 12 months since diagnosis. Of the remaining patients, 7 (54%) survived at least 1 year. The extent of surgery performed, dose of radiotherapy administered, subclass of lymphoma diagnosed, or location(s) of involvement within the CNS did not influence survival. Treatment rarely caused a dramatic improvement in performance status despite objective signs of response. New treatment strategies are needed to improve the management of these tumors.
Asunto(s)
Neoplasias Encefálicas , Linfoma no Hodgkin , Adulto , Anciano , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/terapia , Femenino , Humanos , Linfoma no Hodgkin/diagnóstico por imagen , Linfoma no Hodgkin/patología , Linfoma no Hodgkin/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Tomografía Computarizada por Rayos XRESUMEN
Eleven cases of atypical carcinoid (AC) of the lung were identified during an eight-year period. Their clinical features and treatment responses were contrasted with our experience at Vanderbilt with small cell lung cancer (SCLC) and a literature review of typical bronchial carcinoids (TC). Clinically, there were no features to distinguish AC from TC except for age at diagnosis (59 vs 49 years). Atypical carcinoid was similar to SCLC with respect to many clinical features, although female sex, absence of smoking history and localized disease at presentation were more common in AC. Pathologically, these tumors were distinguished by cellular atypia, necrosis, architectural disorder, or increased mitotic rate in the presence of a recognizable carcinoid pattern. Immunoperoxidase staining revealed no difference between AC and TC or SCLC. Atypical carcinoid of the lung represents a distinct clinicopathologic disease.
Asunto(s)
Tumor Carcinoide/patología , Neoplasias Pulmonares/patología , Adulto , Anciano , Tumor Carcinoide/terapia , Carcinoma Adenoide Quístico/patología , Carcinoma Adenoide Quístico/terapia , Terapia Combinada , Humanos , Neoplasias Pulmonares/terapia , Persona de Mediana EdadRESUMEN
This report describes a 49-year-old man with hypercalcemia and seminoma. His serum calcitriol (1,25-dihydroxy-vitamin D) level was markedly elevated. Additional endocrine evaluation revealed a normal serum phosphate level, hypercalciuria, and normal serum levels of immunoreactive parathyroid hormone. Serum calcium and calcitriol levels returned to normal following partial resection and successful combination chemotherapy. The association of hypercalcemia and elevated serum calcitriol levels has been previously described in a few patients with malignant lymphoma, but, to our knowledge, not in patients with solid tumors. The mechanism of hypercalcemia in this patient is not proved, but available evidence suggests calcitriol as the mediator.