RESUMEN
PURPOSE: In preclinical experiments, interferon alfa modulates the anticancer activity of fluorouracil (5-FU) and cisplatin (CDDP). To test this effect clinically in patients with recurrent or metastatic head and neck cancer (RMHNC), a multicenter randomized controlled trial with CDDP and 5-FU with or without interferon alfa-2b (IFNalpha) was performed. PATIENTS AND METHODS: Eligible patients had histologically confirmed RMHNC; a good performance status; measurable disease; adequate bone marrow, hepatic, and renal function; no prior chemotherapy for recurrent or metastatic disease; only one chemotherapy regimen administered with previous local therapy; and a treatment-free interval of at least 3 months following previous local therapy. Patients were randomized and stratified according to treatment center, and prior radiotherapy and chemotherapy. The treatment regimen consisted of CDDP 100 mg/m2 on day 1 and 5-FU 1,000 mg/m2/d by continuous infusion for 96 hours (days 1 to 4), without (arm A) or with (arm B) IFNg alpha 3 x 10(6) U/d subcutaneously on days 1 to 5. Cycles were repeated every 21 days. RESULTS: One hundred twenty-two patients were entered on each arm. The response rate (RR) was similar in both arms (arm A: complete response [CR] 10.7%, partial response [PR] 36.4%; arm B: CR 6.8%, PR 31.6%) (.70 < P < .50). There was no difference in median survival between the two arms (arm A 6.3 months v arm B 6.0 months; P = .49). Anorexia, fever, leukopenia, and thrombocytopenia grade III to IV were significantly more frequent in the IFNalpha arm. CONCLUSION: Modulation of CDDP and 5-FU with IFNalpha as used in this study does not improve the RR or the median survival in patients with RMHNC. Patients on both study arms had a poor prognosis, which indicates the need for novel therapies.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Interferón-alfa/administración & dosificación , Recurrencia Local de Neoplasia/tratamiento farmacológico , Adulto , Anciano , Cisplatino/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Interferón alfa-2 , Masculino , Persona de Mediana Edad , Proteínas Recombinantes , Inducción de Remisión , Análisis de SupervivenciaRESUMEN
Inhibitors of aromatase are useful for treatment of estrogen-dependent breast cancer and as probes for study of normal physiology. Inhibitors of this enzyme with more favorable properties are necessary since the most extensively utilized inhibitor, aminoglutethimide, lacks specificity and causes frequent side effects. The present study compared the potency and specificity of a new aromatase inhibitor, CGS-16949A, with that of aminoglutethimide in a variety of in vitro enzyme preparations. CGS-16949A blocked aromatase by 50% in human breast cancer homogenates, live breast cancer cells, human placental microsomes and porcine ovarian microsomes at concentrations of 0.008 to 0.02 microM. In contrast, concentrations of 10-25 microM of aminoglutethimide were required to inhibit aromatase similarly in these tissues. For human placental microsomes, the Ki for CGS 16949A was 0.17 nM and for aminoglutethimide, 0.54 microM. Preincubation studies indicated that CGS-16949A acts by a competitive inhibitory mechanism and not by "suicide inhibitory" properties. With respect to specificity, CGS-16949A had no effect on cholesterol side-chain cleavage activity in rat testicular mitochondria. A 54% reduction in enzyme activity was observed in adrenal mitochondria but only at concentrations five orders of magnitude higher (i.e. 100 microM) than required to inhibit aromatase. In contrast, 10 microM concentrations of aminoglutethimide blocked cholesterol side-chain cleavage activity in rat testicular and adrenal mitochondria by 67 and 91%, respectively. These data suggest that CGS-16949A has favorable properties as a specific and potent aromatase inhibitor.
Asunto(s)
Aromatasa/metabolismo , Neoplasias de la Mama/enzimología , Inhibidores Enzimáticos/farmacología , Imidazoles/farmacología , Nitrilos/farmacología , Ovario/enzimología , Placenta/enzimología , Animales , Fadrozol , Femenino , Humanos , Ovario/efectos de los fármacos , Placenta/efectos de los fármacos , PorcinosRESUMEN
The aim of the study was to assess the value of routine bone scintigrams, independent of the primary tumor stage or the presence of symptoms, in the postsurgical follow-up of breast cancer patients for the early detection of bone metastases. For this purpose 1,000 patients with postsurgical breast cancer without previous documentation of metastatic disease, who were admitted to the special oncology hospital, Onkologische Klinik Bad Trissl, entered a prospective study in 1987-1988. The parameters followed were the TNM stage of the primary tumor, the presence of pain, bone pain as revealed by a thorough physical examination, and the patient's history for the assessment of risk factors. In addition, a whole-body skeletal scintigram, supplementary X-rays, and additional diagnostic measures were performed, if necessary, to detect bone metastases. It was shown that in 856 of 894 patients (groups 1-6) without clinical symptoms, the clinical examination and radiological and scintigraphic diagnostic measurements, demonstrating the absence of bone metastases, gave matching results, but in 12 of the 894 patients the results of all examinations remained questionable. In another 12 of the 894 patients (groups 1-3) radiological and/or scintigraphical evidence for the presence of bone metastases was found. In 14 of 79 cases (groups 7-10) with clinically suspicious symptoms these were proven to be signs of metastases by subsequent scintigrams, supplementary X-rays, and additional diagnostic measures. In 65 of the 79 patients with clinically suspicious symptoms, bone metastases could not be confirmed by obtaining bone scintigrams or X-rays while in the other 14 patients (groups 9 and 10) evidence for the presence of bone metastases was found in the scintigrams and/or X-rays. However, 10 of these 14 patients were high-risk patients for developing bone metastases as they had axillary lymph node infiltration. The other 4 patients were of the low-risk group as they had positive receptor status or no axillary lymph node infiltration at the time of primary diagnosis. In 13 of 27 patients (groups 11-14) with clinical symptoms indicating the presence of bone metastases this diagnosis was confirmed by scintigrams and/or X-rays (groups 11 and 12), while it was possible to exclude the presence of bone metastases in spite of the symptoms in 11 of the 27 patients. In the other 3 patients the results of the additional examinations remained questionable.(ABSTRACT TRUNCATED AT 400 WORDS)
Asunto(s)
Neoplasias Óseas/diagnóstico , Neoplasias de la Mama , Neoplasias Óseas/secundario , Huesos/diagnóstico por imagen , Femenino , Estudios de Seguimiento , Humanos , Estadificación de Neoplasias , Estudios Prospectivos , Radiografía , Cintigrafía , Factores de RiesgoAsunto(s)
Traumatismos en Atletas/cirugía , Heparina/efectos adversos , Traumatismos de la Rodilla/cirugía , Complicaciones Posoperatorias/etiología , Trombocitopenia/inducido químicamente , Tromboflebitis/inducido químicamente , Adulto , Coagulación Intravascular Diseminada/inducido químicamente , Relación Dosis-Respuesta a Droga , Heparina/administración & dosificación , Humanos , Embolia y Trombosis Intracraneal/inducido químicamente , Masculino , Complicaciones Posoperatorias/tratamiento farmacológico , Tromboflebitis/tratamiento farmacológicoRESUMEN
In a 59 year-old woman, polychemotherapy with cyclophosphamide and mitoxantrone was started because of liver and bone marrow metastases following operative treatment of breast cancer with subsequent X-ray treatment in 1982. Three weeks after the fourth cycle of polychemotherapy multiple small, firm, reddish papules and pustules developed on the lymphedematous right arm. Histology revealed a dense, well-circumscribed granulocytic infiltrate around the acrosyringial part of the sweat gland duct. Skin lesions cleared completely after the chemotherapy had been changed to cyclophosphamide, methotrexate, and 5-FU. The purpose of our report is to present this largely unknown distinct clinicopathologic entity caused by anthracyclines.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Glándulas Ecrinas/efectos de los fármacos , Mitoxantrona/efectos adversos , Enfermedades de las Glándulas Sudoríparas/inducido químicamente , Glándulas Sudoríparas/efectos de los fármacos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Combinada , Femenino , Humanos , Inflamación , Persona de Mediana Edad , Mitoxantrona/administración & dosificación , Neutrófilos/efectos de los fármacosRESUMEN
Since curative treatment of advanced breast cancer is still beyond our reach, the importance of reducing overall toxicity of systemic treatment must be stressed. This seems to be possible by adapting the form and intensity of therapy to the prognosis and stage of disease and by using drugs exhibiting high antitumoral efficacy combined with low systemic toxicity. In 475 patients with metastatic breast cancer, we initiated a prognosis-oriented therapeutic strategy. We developed a prognostic score so as to classify patients into 'high' and 'low' risk groups. In this way we were able to separate patients into two groups with statistically different survival times. In addition, we found that the impact of the first polychemotherapy on survival is different when comparing patient with favourable and unfavourable prognostic scores. Patients with favourable prognostic factors had exactly the same survival time independent of tumour progression, stable disease or even partial remission. Only patients achieving a complete remission survived longer. In contrast, patients with unfavourable prognostic factors apparently benefited from chemotherapy. Patients achieving stable disease or objective tumour remission had a significantly longer survival time than those patients with immediate tumour progression. Additionally, for most of the patients in this group, chemotherapy induced a transient stabilization or improvement of tumour induced symptoms. Therefore, we conclude that chemotherapy of advanced breast cancer is necessary. However, to reduce overall toxicity, it must be planned and administered according to the prognostic picture of the individual patient.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Humanos , PronósticoAsunto(s)
Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Medroxiprogesterona/análogos & derivados , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Medroxiprogesterona/uso terapéutico , Acetato de Medroxiprogesterona , Metástasis de la Neoplasia , PronósticoRESUMEN
The protective effect of high-titer anti-lipid A hyperimmune globulin with respect to the course of the disease and the mortality rate was studied in patients with septicemia verified by positive blood cultures. Six patients were treated with anti-lipid A in an open study. Dramatic improvement in fever curves and clinical condition in some of the patients encouraged us to start a randomized double blind study. So far, 17 patients have entered the study, 16 of whom were evaluable. Immediately after a positive blood culture was found, patients received either high doses of anti-lipid A or placebo (saline solution) on two subsequent days. Before and after each infusion blood samples were taken in order to assess serum bactericidal activity and anti-lipid A titers. Because of the still small numbers of patients the results of both studies were summarized. In all patients treated with anti-lipid A clear-cut increases in anti-lipid A titers were shown. Patients with repeated gram-negative infections showed higher median anti-lipid A titers than patients without such a history. The patients treated with anti-lipid A immune globulin ran a significantly milder course than the placebo group. The severe signs of septic shock were reversed in seven of 15 patients on anti-lipid A compared to two of seven patients treated with placebo. In the anti-lipid A-treated group, three of 15 patients died, and in the placebo group two of seven. This difference is not statistically significant.
Asunto(s)
Infecciones Bacterianas/terapia , Inmunización Pasiva , Lípido A/inmunología , Lipopolisacáridos/inmunología , Choque Séptico/terapia , Anciano , Anciano de 80 o más Años , Anticuerpos Antibacterianos/análisis , Infecciones Bacterianas/inmunología , Ensayos Clínicos como Asunto , Método Doble Ciego , Bacterias Gramnegativas/inmunología , Humanos , Distribución Aleatoria , Choque Séptico/inmunologíaRESUMEN
The protective effect of high-titer anti-lipid A hyperimmune globulin with respect to the course of the disease and the mortality rate was studied in patients with septicemia verified by positive blood cultures. Six patients were treated with anti-lipid A in an open study. Dramatic improvement in fever curves and clinical condition in some of the patients encouraged us to start a randomized double blind study. So far, 17 patients have entered the study, 16 of whom were evaluable. Immediately after a positive blood culture was found, patients received either high doses of anti-lipid A or placebo (saline solution) on two subsequent days. Before and after each infusion blood samples were taken in order to assess serum bactericidal activity and anti-lipid A titers. Because of the still small numbers of patients the results of both studies were summarized. In all patients treated with anti-lipid A clear-cut increases in anti-lipid A titers were shown. Patients with repeated gram-negative infections showed higher median anti-lipid A titers than patients without such a history. The patients treated with anti-lipid A immune globulin ran a significantly milder course than the placebo group. The severe signs of septic shock were reversed in seven of 15 patients on anti-lipid A compared to two of seven patients treated with placebo. In the anti-lipid A-treated group, three of 15 patients died, and in the placebo group two of seven. This difference is not statistically significant.