RESUMEN
To evaluate the efficacy and safety of Navoban (tropisetron) three different Nordic multicentre trials were conducted during the period 1988-92. In all, 1050 patients were recruited from 15 centres. In the first study, Navoban monotherapy was compared with a high-dose metoclopramide cocktail. In the second, Navoban +/- dexamethasone was evaluated for those patients not fully protected by Navoban alone. In the third trial, Navoban was evaluated for various chemotherapy regimens, for long-term efficacy, and for various risk groups of patients. Spontaneous intercycle variations were also evaluated. Navoban was found to be as effective as the antiemetic cocktail but with a more favourable spectrum of side effects and a simpler schedule of administration. Navoban was more effective during the acute than the delayed phase. Addition of dexamethasone significantly improved prevention of both acute and delayed emesis. Long term efficacy seemed to be stable up to 10 cycles of chemotherapy. Patients treated with noncisplatin regimens showed significantly higher protection rates than patients treated with cisplatin. Various cancer diagnoses and cytostatic agents were also evaluated. Gender and age were important risk factors. Navoban was found to be an efficacious antiemetic agent, especially regarding acute nausea and vomiting. Addition of a corticosteroid significantly improved the effect during highly emetogenic chemotherapy. The role of Navoban for delayed emesis must be evaluated in future trials. The two most common side effects were headache and constipation. Overall, Navoban was well tolerated and patient compliance with the drug was high.
Asunto(s)
Antieméticos/uso terapéutico , Antineoplásicos/efectos adversos , Dexametasona/uso terapéutico , Indoles/uso terapéutico , Náusea/prevención & control , Vómitos/prevención & control , Antineoplásicos/uso terapéutico , Método Doble Ciego , Quimioterapia Combinada , Femenino , Humanos , Masculino , Náusea/inducido químicamente , Neoplasias/tratamiento farmacológico , Factores de Riesgo , Suecia , Tropisetrón , Vómitos/inducido químicamenteRESUMEN
In a double-blind, randomised, multicentre study, the efficacy and tolerability of tropisetron and a combination of tropisetron and dexamethasone were compared for the control of nausea and vomiting induced by cisplatin in patients previously not entirely protected by tropisetron monotherapy. In all, 160 women with gynaecological cancers were studied during two consecutive courses of cisplatin-containing chemotherapy. During the first course (the screening course), all patients received tropisetron monotherapy [5 mg intravenous (i.v.) on day 1 and 5 mg orally on days 2-6] as antiemetic treatment. During the second course (the test course), tropisetron was compared with a combination of tropisetron and dexamethasone (20 mg i.v. on day 1 and 4.5 mg twice daily on days 2-6). This part of the study was double-blind, randomised and placebo-controlled. Candidates for randomisation were patients with partial control of nausea (< 12 h of nausea) or partial control of vomiting (1-4 episodes of vomiting) during the screening course. Patients with complete control of nausea and vomiting in the screening course continued with tropisetron monotherapy; patients with treatment failure received open rescue treatment in course 2. Total control of acute nausea was achieved in 37% of the tropisetron + placebo group and in 75% of the tropisetron + dexamethasone group (P = 0.001). Significantly more patients on tropisetron-dexamethasone than on tropisetron-placebo were also free of delayed nausea. Acute vomiting was prevented in 40% of the patients in the placebo group and in 75% in the dexamethasone group (P = 0.001). Delayed vomiting was also significantly less frequent in dexamethasone-treated patients than in placebo-treated patients. Tropisetron was well tolerated both as monotherapy and in combination with dexamethasone. The most frequent adverse events were headache (34%), constipation (12.5%) and fatigue (12.5%). Adding high doses of a corticosteroid did not induce further adverse events or disregulate concurrent diseases.
Asunto(s)
Antieméticos/uso terapéutico , Cisplatino/efectos adversos , Dexametasona/uso terapéutico , Indoles/uso terapéutico , Náusea/prevención & control , Vómitos/prevención & control , Adulto , Anciano , Anciano de 80 o más Años , Antieméticos/efectos adversos , Método Doble Ciego , Quimioterapia Combinada , Femenino , Neoplasias de los Genitales Femeninos/tratamiento farmacológico , Humanos , Persona de Mediana Edad , Náusea/inducido químicamente , Tropisetrón , Vómitos/inducido químicamenteRESUMEN
BACKGROUND: Chemotherapy-induced emesis is one of the most disturbing side effects in cancer therapy. Thus, antiemetic treatment is a mandatory adjunct in emetogenic chemotherapy. METHODS: Tropisetron (Navoban, Sandoz Pharma Ltd., Basel, Switzerland), a new 5-HT3 receptor antagonist, was compared in a randomized multicenter trial with a high-dose metoclopramide-dexamethasone cocktail for the prevention of nausea and emesis during cisplatin-containing chemotherapy. Two hundred fifty-nine chemotherapy-naive patients were included and followed during two consecutive courses. The main cancer types were gynecologic tumors, followed by lung cancer, head and neck cancer, and bladder cancer. The cisplatin dose usually was in the range of 50-89 mg/m2. The efficacy and quality of life assessments and the safety recordings were done during the first 6 days of both courses of chemotherapy. RESULTS: Acute vomiting was prevented in 63-64% of patients by both antiemetic regimens. The total rate of control of vomiting increased from 63% on day 1 to 93% on day 6 in the group receiving tropisetron. Acute nausea was prevented in 40% of the patients with tropisetron monotherapy and in 61% of patients receiving the antiemetic cocktail. With regard to delayed nausea, there were no significant differences between the two antiemetic regimens. Mild headache and constipation were more frequently associated with tropisetron, and extra-pyramidal side effects and sedation were associated with the antiemetic cocktail. CONCLUSIONS: Tropisetron was easier to administer and better tolerated than the cocktail, and it seems to be a highly efficacious and safe new antiemetic drug.
Asunto(s)
Antieméticos/uso terapéutico , Cisplatino/efectos adversos , Indoles/uso terapéutico , Metoclopramida/uso terapéutico , Náusea/tratamiento farmacológico , Vómitos/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Antieméticos/efectos adversos , Femenino , Humanos , Indoles/efectos adversos , Masculino , Metoclopramida/efectos adversos , Persona de Mediana Edad , Náusea/inducido químicamente , Neoplasias/tratamiento farmacológico , Calidad de Vida , Tropisetrón , Vómitos/inducido químicamenteRESUMEN
In a non-randomized clinical trial, combined intraperitoneal therapy with recombinant interferon alpha-2b (20-50 MU) and mitoxantrone (20-50 mg) was studied for recurrent ovarian cancer with ascites. Altogether 19 patients were treated. After primary operation, all patients had received intravenous chemotherapy, 16 of which included cisplatin. One patient had complete response, seven patients partial response, four no change and seven progressive disease. The mean duration of the responses was 5+ months (range 1-12), and mean survival time 4.5+ months (range 1-14+). Eight patients had side effects (flu-like symptoms, dyspnea, abdominal pain, vomiting, diarrhea, fever and bowel obstruction). It was concluded that the formation of ascites in refractory ovarian cancer can be reduced with intraperitoneal administration of interferon alpha-2b and mitoxantrone, with tolerable side effects.
Asunto(s)
Interferón-alfa/administración & dosificación , Mitoxantrona/administración & dosificación , Recurrencia Local de Neoplasia/terapia , Neoplasias Ováricas/terapia , Adulto , Anciano , Ascitis/mortalidad , Ascitis/patología , Ascitis/terapia , Terapia Combinada , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Inyecciones Intraperitoneales , Interferón alfa-2 , Interferón-alfa/efectos adversos , Persona de Mediana Edad , Mitoxantrona/efectos adversos , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/patología , Proteínas Recombinantes , Tasa de SupervivenciaRESUMEN
A multicentre study was performed at four oncology centres in Sweden, in 160 chemotherapy-naive women, primarily with ovarian or endometrial carcinomas. Abdominal surgery preceded chemotherapy in 146 (91%) women, and another 39 (24%) women had a history of radiotherapy. The chemotherapy regimens contained cisplatin (50-100 mg/m2), in combination with a variety of other agents. In Course 1, all patients received tropisetron (5 mg i.v. Day 1; 5 mg p.o. Days 2-6) and 84% of patients achieved total or partial control of vomiting; 95% of patients achieved total or partial control of nausea during the first 24 hours. Vomiting was least successfully controlled on Day 2 (73% total or partial control) and Days 2-4 for the control of nausea (81, 83, 88% total or partial control, respectively). Patients with partial response in Course 1 (39% of patients) were randomized to addition of dexamethasone or placebo in Course 2. In Course 2, tropisetron plus dexamethasone (Group B2) prevented acute vomiting in 75% of patients, compared with 40% of patients receiving tropisetron plus placebo (Group B1). Over the entire 6 days, there was no vomiting at all in 54% and 20% of B2 and B1 patients, respectively. In Course 2, acute nausea was prevented in 75% of patients (receiving B1) and in 37% of patients (receiving B2). For nausea, over the complete 6 days, the figures were 64% and 3% (p < 0.001). This indicated that patients with incomplete control of emesis in Course 1 benefited from the addition of dexamethasone, provided that it was added for each of the 6 days studied.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Antieméticos/uso terapéutico , Dexametasona/uso terapéutico , Indoles/uso terapéutico , Náusea/prevención & control , Antagonistas de la Serotonina/uso terapéutico , Vómitos/prevención & control , Adulto , Anciano , Anciano de 80 o más Años , Antieméticos/administración & dosificación , Cisplatino/efectos adversos , Dexametasona/administración & dosificación , Quimioterapia Combinada , Femenino , Humanos , Indoles/administración & dosificación , Persona de Mediana Edad , Náusea/inducido químicamente , Antagonistas de la Serotonina/administración & dosificación , Tropisetrón , Vómitos/inducido químicamenteRESUMEN
The response of plasma immunoreactive beta-endorphin (ir-beta E) and corticotropin to isometric exercise was studied in 10 women with pregnancy-induced hypertension (PIH) and in nine healthy women subjected to a handgrip test in the third trimester of gestation. The mean basal concentration of corticotropin was higher in the PIH than in the control group, 3.8 +/- 0.3 (SE) pmol/l and 2.2 +/- 0.2 pmol/l, respectively (p = 0.002). No significant difference was found in the basal ir-beta E level, 6.9 +/- 0.9 pmol/l and 6.1 +/- 1.0 pmol/l, respectively. In response to the handgrip test, the corticotropin and ir-beta E concentrations rose significantly in all subjects (p = 0.001 and p = 0.02, respectively) without any significant differences between the groups. These findings indicate that an isometric exercise is sufficient to increase the secretion of ir-beta E and corticotropin during pregnancy. Increased basal concentration of corticotropin in women with PIH may be explained by significantly increased circulating corticotropin-releasing hormone, 1451 +/- 323 pmol/l, as compared to 528 +/- 190 pmol/l in the control group.
Asunto(s)
Hormona Adrenocorticotrópica/sangre , Ejercicio Físico , Hipertensión/sangre , Complicaciones Cardiovasculares del Embarazo , Embarazo , betaendorfina/sangre , Femenino , Humanos , Tercer Trimestre del EmbarazoRESUMEN
Corticotropin-releasing hormone was discovered in the placenta, and its concentration in the maternal plasma was found to increase greatly during the latter half of pregnancy. We studied the concentration of immunoreactive corticotropin-releasing hormone in amniotic fluid in 59 uncomplicated and in 73 complicated pregnancies. The mean (+/- SE) value of corticotropin-releasing hormone in amniotic fluid in uncomplicated pregnancies was significantly higher in the third (24.1 +/- 3.3 pmol/L) than in the second (9.1 +/- 0.7 pmol/L) trimester, but no change was found during labor. In groups matched by gestational age, larger mean values of corticotropin-releasing hormone and cortisol were observed in the group in which the lecithin/sphingomyelin ratio was greater than 2 or the phosphatidylglycerol test was positive than in the group with a lecithin/sphingomyelin ratio less than 2 or a negative phosphatidylglycerol test result. In samples taken at an interval of 1 to 3 weeks, concomitant increases in corticotropin-releasing hormone and cortisol levels were found with the appearance of phosphatidylglycerol. Concentrations of corticotropin-releasing hormone in amniotic fluid were elevated in patients with diabetes and in women with preeclampsia and intrauterine growth retardation. We conclude that the intrauterine release of corticotropin-releasing hormone increases during the last trimester. This may stimulate the fetal pituitary-adrenal axis and promote fetal maturation.
Asunto(s)
Líquido Amniótico/metabolismo , Hormona Liberadora de Corticotropina/metabolismo , Trabajo de Parto/metabolismo , Pulmón/embriología , Embarazo/metabolismo , Femenino , Retardo del Crecimiento Fetal/metabolismo , Madurez de los Órganos Fetales , Humanos , Hidrocortisona/metabolismo , Fosfatidilcolinas/metabolismo , Fosfatidilgliceroles/metabolismo , Esfingomielinas/metabolismoRESUMEN
Using a specific radioimmunoassay the concentrations of beta-endorphin, beta-lipotropin and corticotropin in maternal plasma were studied during pregnancy and in the early puerperium. Compared with the values in nonpregnant women, levels of beta-endorphin and beta-lipotropin were slightly lower in the first and second trimesters; corticotropin showed no difference in the first trimester. The concentrations of all these peptides increased towards term, most markedly in the case of corticotropin. The diurnal variation was studied near term and again in the early puerperium. beta-Endorphin and corticotropin showed a parallel diurnal variation. The values in the morning and during the day were slightly higher during pregnancy than in the puerperium, whereas the values at midnight were similar. After vaginal delivery, a rapid and parallel decrease in the plasma levels of beta-endorphin, beta-lipotropin and corticotropin was found. In elective cesarean section, the values were highest 30 min after delivery, reflecting surgical stress, and then the decrease was similar to that after vaginal delivery. Thus parallel changes in the plasma levels of beta-endorphin, beta-lipotropin and corticotropin during pregnancy and in the early puerperium were found, which can be explained by their origin from a common precursor peptide, pro-opiomelanocortin. The rise in the plasma levels of corticotropin and endorphins near term and the exaggerated diurnal variation is probably a reflection of a maternal adaptation to stress.
Asunto(s)
Hormona Adrenocorticotrópica/sangre , Ritmo Circadiano , Lipoproteínas LDL/sangre , Periodo Posparto/sangre , Embarazo/sangre , betaendorfina/sangre , Adulto , Femenino , HumanosRESUMEN
Concentrations of immunoreactive corticotropin releasing factor (CRF) and corticotropin (ACTH) in the plasma were studied in healthy pregnant women. Concentration of CRF was near the detection limit of the assay (2.5 pmol/l) until the 16th week of pregnancy, increasing thereafter significantly towards term: the mean values (+/- S.E.) at weeks 8-11, 12-15, 16-19, 20-23, 24-27, 28-31, 32-35, and 36-40 were 2.9 +/- 0.42, 2.9 +/- 0.72, 5.2 +/- 1.1, 10.2 +/- 5.8, 14.6 +/- 2.0, 32.8 +/- 4.8, 63.6 +/- 9.2, and 187 +/- 39 pmol/l, respectively. The mean concentration of CRF did not increase during labor, and it decreased rapidly after delivery. On the contrary, the mean plasma level of ACTH increased only slightly during late pregnancy, but during labor the increase was significant. These findings suggest that CRF in maternal circulation is not primarily involved in the regulation of maternal ACTH secretion, and the stress of labor does not increase the release of CRF, which probably originates mainly from the placenta.
Asunto(s)
Hormona Adrenocorticotrópica/sangre , Hormona Liberadora de Corticotropina/sangre , Trabajo de Parto/sangre , Periodo Posparto/sangre , Embarazo/sangre , Adulto , Femenino , Humanos , Primer Trimestre del Embarazo , Segundo Trimestre del Embarazo , Tercer Trimestre del Embarazo , RadioinmunoensayoRESUMEN
The purpose of this study was to clarify the endocrine regulation of the adolescent menstrual cycle, especially the relationships between ovarian follicular development, luteal phase progesterone secretion, and function of the hypothalamic-pituitary unit. One menstrual cycle of each of 17 women who were 15 and 16 years of age and 12 women who were 25 to 35 years of age was characterized by ultrasonography and hormone measurements. In both groups there was a close correlation between follicle size and serum estradiol concentrations. In the adolescents, follicle development was slower, and an eventual ovulation took place from a smaller follicle than in the older group. The immediate preovulatory follicle size correlated with the maximal serum progesterone concentration during the luteal phase. Late follicular development in adolescents may be related to the slow increase of serum follicle-stimulating hormone concentrations early in the cycle.
Asunto(s)
Estradiol/sangre , Hormona Folículo Estimulante/sangre , Hormona Luteinizante/sangre , Ciclo Menstrual , Folículo Ovárico/fisiología , Progesterona/sangre , Adolescente , Adulto , Femenino , Humanos , UltrasonografíaRESUMEN
Concentration of beta-endorphin in relation to the mode of delivery and anesthesia was studied in maternal and umbilical cord plasma in 30 healthy women at term pregnancy. At elective cesarean section under epidural anesthesia, the mean maternal beta-endorphin level rose from 9.8 +/- 2.7 pmol/L (SE) before induction to 15.5 +/- 3.7 pmol/L at the time of delivery (P less than .02). Under general anesthesia the mean beta-endorphin level increased more, from 14.6 +/- 7.2 to 34.4 +/- 7.8 pmol/L (P less than .02), reaching the mean beta-endorphin value of the second stage of normal labor, 39.4 +/- 7.0 pmol/L. In the cord arterial and venous plasma, the mean beta-endorphin value was significantly higher after spontaneous labor (40.9 +/- 11 and 40.1 +/- 9.2 pmol/L, respectively) than at elective cesarean section under epidural (14.3 +/- 1.9 and 12.4 +/- 3.6 pmol/L, respectively) or general anesthesia (11.9 +/- 2.2 and 13.4 +/- 2.2 pmol/L, respectively). Thus cesarean section under general anesthesia proved to be more stressful for the mother than that under epidural anesthesia, when beta-endorphin release is used as the measure of stress. The mode of anesthesia did not seem to influence the plasma beta-endorphin level in the newborn infant. Normal delivery by vaginal route increased the release of beta-endorphin both to the maternal and the fetoplacental circulation.
Asunto(s)
Cesárea , Endorfinas/sangre , Sangre Fetal/análisis , Trabajo de Parto , Anestesia Epidural , Anestesia General , Anestesia Obstétrica , Femenino , Humanos , Recién Nacido , Embarazo , betaendorfinaRESUMEN
beta-Endorphin (beta-E) takes part in the regulation of luteinizing hormone (LH) and prolactin secretion, but little is known about its role in the menstrual cycle. Using a specific assay, plasma concentration of beta-E was followed in healthy women in the periovulatory period and before and during menstruation. The mean concentration of beta-E in the eight women studied showed an increase at the midcycle, being 3.2 +/- 0.5 (standard error) pmol/l on day LH -1 and rising to 4.6 +/- 0.7 pmol/l on day LH 0 and further to 7.5 +/- 1.2 pmol/l on day LH +1. Thereafter, the mean beta-E level remained at 5.3 +/- 0.8 pmol/l and 5.2 +/- 0.4 pmol/l on days LH +2 and LH +3, respectively. Ten additional women were studied before and during menstruation. The highest mean plasma concentration of beta-E, 5.1 +/- 0.9 pmol/l, was found at the onset of menstruation, declining to 3.3 +/- 0.6 pmol/l and 2.9 +/- 0.6 pmol/l on the second and fifth days of menstruation, respectively. These findings suggest that beta-E secretion increases at the time of ovulation. At the onset of menstruation, pain may increase endorphin secretion.
Asunto(s)
Endorfinas/sangre , Ciclo Menstrual , Adulto , Femenino , Humanos , betaendorfinaRESUMEN
Wertheim radical hysterectomy combined with pelvic lymphadenectomy was performed at the Helsinki University Central Hospital on 132 women of whom 120 had cervical carcinoma from Stage IA to early IIB and 12 had endometrial carcinoma Stage II. None of the patients died or had severe complications during their hospitalisation. The left ureter was accidently transected in two patients and both were corrected immediately. Wound complications occurred in 16 patients (12%). The high incidence of wound complications is probably partly related to the low-dose heparin prophylaxis. The initial clinical staging was found to be correct in 85% of the cases. Five cases were under-staged. All ten patients cases of early Stage IIB were over-staged, none of whom had parametrial invasion. The predictive value of lymphangiography was low, 14% in histologically positive cases and 89% in negative cases of lymph node metastases. Lymphangiography proved to be only of value in facilitating complete lymph node dissection. Intra-operative lymphangiographic control revealed radio-positive nodes and lead to further dissection in 30 patients (24%).
Asunto(s)
Histerectomía/métodos , Escisión del Ganglio Linfático , Neoplasias del Cuello Uterino/cirugía , Neoplasias Uterinas/cirugía , Adulto , Anciano , Femenino , Humanos , Complicaciones Intraoperatorias , Metástasis Linfática , Linfografía , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias del Cuello Uterino/patología , Neoplasias Uterinas/patologíaRESUMEN
Plasma concentration of beta-endorphin was observed during labor in 16 women and correlated with pain assessed subjectively using pain scores. Ten women did not receive any medication during the follow-up. A concomitant increase in pain score and plasma beta-endorphin level was found with advancing labor. In the remaining six women, epidural anesthesia was used to relieve pain. During epidural anesthesia, plasma beta-endorphin levels and pain scores decreased concomitantly. The same effect was found after a repeated dose of the anesthetic. These findings showed a correlation between pain and the secretion of beta-endorphin during labor, but the mode of action of beta-endorphin remains unsolved.