RESUMEN
BACKGROUND: Mogamulizumab was compared with vorinostat in the phase 3 MAVORIC trial (NCT01728805) in 372 patients with relapsed/refractory mycosis fungoides (MF) or Sézary syndrome (SS) who had failed ≥1 prior systemic therapy. Mogamulizumab significantly prolonged progression-free survival (PFS), with a superior objective response rate (ORR) vs. vorinostat. OBJECTIVES: This post hoc analysis was performed to evaluate the effect of baseline blood tumour burden on patient response to mogamulizumab. METHODS: PFS, ORR, time to next treatment (TTNT), skin response (modified Severity-Weighted Assessment Tool [mSWAT]) and safety were assessed in patients stratified by blood classification (B0 [n = 126], B1 [n = 62], or B2 [n = 184], indicating increasing blood involvement). RESULTS: Investigator-assessed PFS was longer for mogamulizumab versus vorinostat across all blood classes, significantly so for B1 and B2 patients. ORR was higher with mogamulizumab than with vorinostat in all blood classification groups and more markedly so with escalating B class (B0: 15.6% vs. 6.5%, P = 0.0549; B1: 25.8% vs. 6.5%, P = 0.2758; B2: 37.4% vs. 3.2%, P < 0.0001). TTNT was significantly longer for patients treated with mogamulizumab versus vorinostat with B1 (12.63 vs. 3.07 months; HR 0.32 [95% CI 0.16-0.67]; P = 0.0018) and B2 (13.07 vs. 3.53 months; HR 0.30 [95% CI 0.21-0.43]; P < 0.0001) blood involvement. In the mogamulizumab arm, 81 patients (43.5%) had ≥50% change in the mSWAT vs. 41 patients (22.0%) with vorinostat; mSWAT improvements with mogamulizumab occurred most often in B1 and B2 patients. Rapid, sustained reductions were seen in CD4+ CD26- cell counts and CD4:CD8 ratios in mogamulizumab patients for all B classes. Treatment-emergent adverse events were less frequent overall with mogamulizumab and similar in frequency regardless of B class. CONCLUSIONS: This post hoc analysis indicates greater clinical benefit with mogamulizumab vs. vorinostat in patients with MF and SS classified as having B1 and B2 blood involvement.
Asunto(s)
Micosis Fungoide , Neoplasias Cutáneas , Anticuerpos Monoclonales Humanizados , Humanos , Recurrencia Local de Neoplasia , Carga TumoralRESUMEN
OBJECTIVE: To investigate potential differences in zibotentan pharmacokinetics between Japanese and Caucasian patients with hormone-resistant prostate cancer (HRPC) following single and multiple dosing. METHODS: In the Japanese study, 18 patients received a single dose of zibotentan 5, 10 or 15 mg followed by 72 h washout before 26 days' once-daily dosing. In the Caucasian study, 21 patients received a single dose of zibotentan 5, 10 or 15 mg followed by 72 h washout before 12 days' once-daily dosing. RESULTS: Pharmacokinetic parameters were similar between populations. Absorption of zibotentan was rapid with maximum plasma concentrations typically achieved within 3 h of dosing. Mean clearance, 17.9 and 18.7 ml/min in Japanese and Caucasian patients, respectively (range 7.0 - 36.3 ml/min in Japanese patients and 7.8 - 29.5 ml/min in Caucasian patients) and volume of distribution, 14.0 and 15.6 l for Japanese and Caucasian patients, respectively (range 7.9 - 29.1 l in Japanese patients and 9.6 - 23.8 l in Caucasian patients) were relatively low, and t1/2 was approximately 12 h (range 5.7 - 18.8 h in Japanese patients and 5.0 - 22.9 h in Caucasian patients) following single dosing. Little accumulation was observed following daily dosing and multiple-dose pharmacokinetics were predictable. Exposure levels achieved in some Japanese patients receiving zibotentan 15 mg were higher than those observed in Caucasian patients, however, this may be due to differences in body weight, as exposure levels were similar when data were normalized for body weight. Zibotentan was well tolerated in both populations. CONCLUSIONS: There are no clinically relevant differences in the disposition and pharmacokinetics of zibotentan between Japanese and Caucasian patients with HRPC.
Asunto(s)
Antineoplásicos/farmacocinética , Neoplasias de la Próstata/tratamiento farmacológico , Pirrolidinas/farmacocinética , Anciano , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Pueblo Asiatico , Peso Corporal , Relación Dosis-Respuesta a Droga , Antagonistas de los Receptores de la Endotelina A , Semivida , Humanos , Japón , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/patología , Pirrolidinas/administración & dosificación , Pirrolidinas/efectos adversos , Distribución Tisular , Población BlancaRESUMEN
BACKGROUND: Supradiaphragmatic radiotherapy (SRT) to treat Hodgkin's lymphoma (HL) at a young age increases the risk of breast cancer (BC). A national notification risk assessment and screening programme (NRASP) for women who were treated with SRT before the age of 36 years was instituted in the United Kingdom in 2003. In this study, we report the implementation and screening results from the largest English Cancer Network. METHODS: A total of 417 eligible women were identified through cancer registry/hospital databases and from follow-up (FU) clinics. Screening results were collated retrospectively, and registry searches were used to capture BC cases. RESULTS: Of the 417 women invited for clinical review, 243 (58%) attended. Of these 417 women, 23 (5.5%) have been diagnosed with BC, a standardised incidence ratio of 2.9 compared with the age-matched general population. Of five invasive BCs diagnosed within the NRASP, none involved axillary lymph nodes compared with 7 of 13 (54%) diagnosed outside the programme (P<0.10). The mean latency for BC cases was 19.5+/-8.35 years and the mean FU duration for those unaffected by BC was 14.6+/-9.11 years (P<0.01), suggesting that those unaffected by BC remain at high risk. Recall and negative biopsy rates were acceptable (10.5 and 0.8%, respectively). CONCLUSIONS: The NRASP appears to detect BC at an early stage with acceptable biopsy rates, although numbers are small. Determination of NRASP results on a national basis is required for the accurate evaluation of screening efficacy in women previously treated with SRT.
Asunto(s)
Neoplasias de la Mama/diagnóstico , Enfermedad de Hodgkin/radioterapia , Tamizaje Masivo/métodos , Neoplasias Inducidas por Radiación/diagnóstico , Neoplasias Primarias Secundarias/diagnóstico , Adulto , Neoplasias de la Mama/etiología , Femenino , Humanos , Mamografía , Persona de Mediana Edad , Radioterapia/efectos adversos , Sistema de Registros , Estudios Retrospectivos , Factores de Riesgo , Sobrevivientes , Reino UnidoRESUMEN
AIMS: To review the outcome of 41 patients with invasive carcinoma of the penis treated with external-beam radiotherapy using a consistent technique and dose. MATERIALS AND METHODS: Forty-one patients with carcinoma of the penis treated at Christie Hospital, Manchester, UK, between 1995 and 2000 were reviewed retrospectively. Radiotherapy was delivered using 4 MV linear accelerators with a dose of 50 Gy or 52.5 Gy in 16 fractions over 22 days. RESULTS: The distribution of patients according to stage was T1=37, T2=4, N0=40, N3=1. Median follow-up was 4.5 years. The local control rate was 62%, nodal relapse-free rate of 88%, relapse-free rate of 51% and overall survival of 88% at 5 years. All recurrences were salvaged by surgery. Penile ulceration occurred in 8% and urethral stenosis requiring dilatation in 29%. There were no penectomies for penile necrosis. CONCLUSION: EBXRT may be offered for T1-2 cancer of the penis with close surveillance to detect local recurrences early for salvage surgery without jeopardising overall survival. It remains an alternative option to penis-preserving surgery and should be discussed in a multidisciplinary setting and with the patient.
Asunto(s)
Carcinoma de Células Escamosas/radioterapia , Recurrencia Local de Neoplasia/radioterapia , Neoplasias del Pene/radioterapia , Pene/efectos de la radiación , Carcinoma de Células Escamosas/cirugía , Humanos , Masculino , Recurrencia Local de Neoplasia/cirugía , Neoplasias del Pene/cirugía , Dosificación Radioterapéutica , Estudios Retrospectivos , Sobrevida , Resultado del TratamientoRESUMEN
The chest radiographs (CXRs) of 110 patients with mediastinal Hodgkin's disease (HD) were reviewed to determine the incidence, degree, and significance of mediastinal abnormalities following treatment. Residual mediastinal abnormalities were defined as either minimal or measurable, and occurred in 64% of all patients at the completion of treatment, but were more common in those with bulky mediastinal disease at presentation (40 of 48, 83%). Fifty-one patients with a mediastinal abnormality at the end of treatment had follow-up films available. Partial or complete regression of the abnormality occurred by 1 year in 30 of these patients (59%). Over a median follow-up of 80.5 months, there were more relapses (13 of 70, 19%) in patients with residual abnormalities following treatment than in those where the mediastinum was considered normal (four of 40, 10%). Measurable abnormality was associated with a higher relapse rate (six of 25, 24%) than minimal abnormality (seven of 45, 16%), but none of these differences were statistically significant. the subsequent relapse rate for patients with persisting abnormality at 1 year was 14%, compared with 17% for patients in whom regression had occurred and 14% in whom the mediastinum had always been considered normal. Considering the whole group, the presence of a mediastinal abnormality following treatment did not predict for relapse, but for the 34 patients treated by chemotherapy (CTR) alone, a residual abnormality was associated with a significantly higher relapse rate (P = .029). We conclude that following mediastinal radiotherapy (XRT) administered either alone or combined with CTR, residual mediastinal abnormalities do not indicate the need for further treatment. However, following CTR alone, such abnormalities may signify persisting disease and we recommend that XRT be considered for these patients.
Asunto(s)
Enfermedad de Hodgkin/diagnóstico por imagen , Neoplasias del Mediastino/diagnóstico por imagen , Mediastino/diagnóstico por imagen , Adolescente , Adulto , Terapia Combinada , Femenino , Enfermedad de Hodgkin/mortalidad , Enfermedad de Hodgkin/terapia , Humanos , Masculino , Neoplasias del Mediastino/mortalidad , Neoplasias del Mediastino/terapia , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Pronóstico , Radiografía TorácicaRESUMEN
PURPOSE: To test the hypothesis that a chemotherapy regimen of relatively low toxicity and 11 weeks' duration (doxorubicin, cyclophosphamide, etoposide, vincristine, bleomycin, and prednisolone [VAPEC-B]) is at least as effective in terms of disease control as 6 months' treatment with chlorambucil, vinblastine, procarbazine, and prednisone/etoposide, vincristine, and doxorubicin (ChlVPP/EVA hybrid), which is associated with a high risk of permanent sterility. PATIENTS AND METHODS: Two hundred eighty-two patients with previously untreated Hodgkin's disease, clinical stages I/II (plus mediastinal bulk and/or B symptoms) and clinical stages III/IV were randomized at three United Kingdom and one Italian center to receive either six monthly cycles of ChlVPP/EVA hybrid or 11 weekly cycles of VAPEC-B. After chemotherapy and a restaging evaluation, radiotherapy was administered to sites of previous bulk or residual radiographic abnormality before patients were observed off treatment. RESULTS: Further accrual to the trial was halted at the planned third interim analysis in September 1996. After a median follow-up of 4.9 years, freedom from progression (FFP), event-free survival (EFS), and overall survival (OS) are all significantly better in the population treated with ChlVPP/EVA than VAPEC-B, where the comparative 5-year results are 82% and 62% (FFP), 78% and 58% (EFS), and 89% and 79% (OS), respectively. The superiority of ChlVPP/EVA was seen in both low-risk and intermediate/high-risk patients, although subset analysis suggested that ChlVPP/EVA and VAPEC-B produce equivalent results in the best-prognosis patients (Hasenclever score Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico
, Enfermedad de Hodgkin/tratamiento farmacológico
, Adolescente
, Adulto
, Anciano
, Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación
, Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos
, Bleomicina/administración & dosificación
, Clorambucilo/administración & dosificación
, Ciclofosfamida/administración & dosificación
, Doxorrubicina/administración & dosificación
, Etopósido/administración & dosificación
, Femenino
, Enfermedad de Hodgkin/patología
, Humanos
, Incidencia
, Italia
, Masculino
, Persona de Mediana Edad
, Estadificación de Neoplasias
, Neoplasias Primarias Secundarias/inducido químicamente
, Prednisolona/administración & dosificación
, Procarbazina/administración & dosificación
, Pronóstico
, Resultado del Tratamiento
, Reino Unido
, Vinblastina/administración & dosificación
, Vincristina/administración & dosificación
RESUMEN
OBJECTIVE: To survey UK urologists and radiation oncologists in the evaluation and treatment of localised prostate cancer in the adjuvant and salvage setting. METHODS: Postal questionnaires were mailed to 292 urologists and 98 radiation oncologists in the UK. RESULTS: In all, 188 (48%) questionnaires were returned. In total, 72/128 (56%) of the urologist respondents and 58/60 (97%) of the oncologist respondents perform routine radical prostate treatment. Among 43 (60%) of the urologist, 40 (69%) recommended adjuvant treatment, which could be radiotherapy, hormonal treatment or combined hormonal and radiation treatment. There is no significant difference between the modality of treatment recommended. The poor prognostic factors that would influence the decision to offer adjuvant treatment include a detectable postoperative PSA, seminal vesicle involvement, positive margins, Gleason score>8 and pathological T3. With regard to the choice of hormonal treatment, most urologists preferred antiandrogens, whereas most oncologists prefer lutienising hormone releasing hormone (LHRH) analogue (P=0.03). Regarding salvage treatment, there is a wide variation in the PSA threshold and number of PSA rises before initiation of investigations and treatment. Significantly more urologists recommended salvage radiotherapy (P=0.02), whereas oncologists recommended combined hormonal radiation therapy (P=0.03). There is a wide variation of practice regarding the duration of hormonal treatment, the type of investigations initiated, range of radiotherapy doses and treatment volumes. CONCLUSION: There is a wide variation in practice among UK clinicians.
Asunto(s)
Quimioterapia Adyuvante/métodos , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/terapia , Hormona Liberadora de Gonadotropina/análogos & derivados , Humanos , Masculino , Pronóstico , Próstata/patología , Antígeno Prostático Específico/metabolismo , Radioterapia/métodos , Terapia Recuperativa , Sensibilidad y Especificidad , Encuestas y Cuestionarios , Factores de Tiempo , Reino UnidoRESUMEN
The mechanisms of hypercalcemia were assessed in 15 patients with humoral hypercalcemia of malignancy (HHM) who had tumors at various stages of progression. In patients with early tumors, bone biopsies were generally normal and the hypercalcemia was due to an elevation in renal tubular resorption of calcium. Conversely, osteoclastic resorption was markedly increased in patients with advanced tumors, particularly those in whom the biopsies were obtained postmortem. Osteoclast surface (Oc.S) correlated positively with the stage of tumor progression (r = 0.80, p less than 0.002), degree of immobility (r = 0.87, p less than 0.002), and level of urinary cyclic AMP excretion (r = 0.60, p less than 0.02). When compared with a group of ambulant patients with primary hyperparathyroidism (HPT), osteoblast surface (Ob.S%) in HHM was depressed (median and range): 1.2% (0-11.6%) versus 5.3% (1.1-32.0%) (p less than 0.001). However, a relatively low Ob.S (4%) and raised Oc.S (43.5%) were also seen in an immobilized patient with severe HPT. These data suggest that the PTH-related peptides currently invoked in the pathogenesis of HHM may initially cause hypercalcemia by enhancing renal tubular calcium resorption. The increase in osteoclastic activity and depression of osteoblastic activity that subsequently occurs is probably due to the combined effects of immobilization and higher circulating levels of PTHrP on the skeleton. However, the release of other bone-resorbing factors by the tumor, which have a depressant effect on osteoblastic activity, remains possible.
Asunto(s)
Hipercalcemia/etiología , Neoplasias/complicaciones , Adulto , Anciano , Resorción Ósea , Femenino , Humanos , Hipercalcemia/metabolismo , Inmovilización , Túbulos Renales/metabolismo , Masculino , Persona de Mediana Edad , Neoplasias/metabolismo , OsteoblastosRESUMEN
A double-blind randomized study of 29 patients with symptomatic Paget's disease was conducted comparing the clinical, biochemical, and histomorphometric responses to 3-month treatment with placebo (10 patients), low-dose disodium etidronate (EHDP) (5-7 mg/kg/day) (10 patients), and low-dose EHDP plus 1 alpha-hydroxyvitamin D3 (1 alpha D3) 0.5 mcg daily (9 patients). In placebo-treated patients no significant changes were observed in symptoms, biochemistry, or bone histomorphometry. Histologically apparent mineralization defects developed after 3 months of therapy in 90% of patients in the EHDP group, compared with 45% of patients in the EHDP/1 alpha D3 group. In 19% of the patients treated with active medication, the mineralization defects in pagetic bone were accompanied by histological evidence of continued osteoclastic resorption. The development of mineralization defects was not related to serum levels of vitamin D metabolites, alkaline phosphatase, or intestinal calcium absorption but did correlate with the occurrence of hyperphosphatemia during treatment, which was most marked in patients treated with EHDP alone. Although mineralization defects were less frequent in the EHDP/1 alpha D3 group, these patients also responded less well symptomatically, thus limiting the potential usefulness of this drug combination in Paget's disease.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Calcitriol/farmacología , Ácido Etidrónico/uso terapéutico , Minerales/metabolismo , Osteítis Deformante/tratamiento farmacológico , Fosfatasa Alcalina/sangre , Creatinina/orina , Método Doble Ciego , Humanos , Hidroxiprolina/orina , Osteítis Deformante/metabolismo , Distribución AleatoriaRESUMEN
The relationship of ischaemic heart disease (IHD) to seasonal and latitude variation has prompted speculation that exposure to the ultraviolet component of solar radiation may reduce IHD risk. This hypothesis was partially tested by exposing 14 post-myocardial infarction patients to a 6 week course of artificial whole-body ultraviolet radiation (UVR). Serum lipoprotein and plasma coagulation factor concentrations were measured before and after the course of UVR. Results were compared with similar measurements from a placebo-controlled group of 13 post-myocardial patients. Despite a more than two-fold rise in mean serum 25-OHD, serum lipoprotein and plasma fibrinogen, antithrombin III and plasminogen concentrations did not change significantly in the UVR group. Significant but minor change in prothrombin time and thrombin time in the placebo group appear unlikely to be of biological significance. Seasonal and latitude variation in these IHD risk factors appear unrelated to corresponding variation in solar UVR exposure.
Asunto(s)
Antitrombina III/metabolismo , Fibrinógeno/metabolismo , Lipoproteínas/sangre , Infarto del Miocardio/sangre , Infarto del Miocardio/radioterapia , Plasminógeno/metabolismo , Rayos Ultravioleta , Terapia Ultravioleta , Antitrombina III/efectos de la radiación , Femenino , Fibrinógeno/efectos de la radiación , Humanos , Lipoproteínas/efectos de la radiación , Masculino , Persona de Mediana Edad , Plasminógeno/efectos de la radiación , Tiempo de Protrombina , Tiempo de Trombina , Irradiación Corporal TotalRESUMEN
PURPOSE: The pivotal step in radiation planning is delineation of the target volume and production of a treatment plan to encompass this. This study assesses the variation of physicians in creation of these volumes. METHODS AND MATERIALS: Three radiologists and eight radiation oncologists outlined the gross tumour volume (GTV) on the planning CT scans of four cases with T3 bladder cancer. In addition, the radiation oncologists (RO) created a planning target volume according to a set protocol for all cases. Volumes were produced and comparison of these volumes and the position of the isocenters were analysed. In addition, the margins allowed were measured and compared. RESULTS: There was a maximum variation ratio (largest to smallest volume outlined) of the GTV in the four cases of 1.74 among radiologists and 3.74 among oncologists. There was a significant difference (p = 0.01) in mean GTV between RO and the radiologists. The mean GTV of the RO exceeded the radiologists by a factor of 1.29 with a mean difference of 13.4 cm3. The variation ratio in PTV among oncologists ranged from 1.25 to 3.33. There was no significant difference in mean PTV values between the two groups of ROs divided by specialization in uro-oncology. The mean variation in location of the isocenter from the centroid of the radiologists' volume in the four cases was from 2.6 to 5.7 mm. There was, however, a wide range of values from 1.4 mm to 24.1 mm. Median margin per case ranged from 14.7 to 18.7 mm. Minimum margins allowed in each case varied from minus 7 mm to 9 mm. CONCLUSION: This study demonstrates significant interphysician variability in producing target volumes and radiation plans for conformal radiotherapy. The scale of this difference is clearly of significance, with up to 3-fold variation in volumes delineated by clinicians. The factors leading to these differences will be further addressed. The existence of such variability, however, clearly needs to be accepted as a factor in the overall uncertainty analysis in conformal radiotherapy planning.
Asunto(s)
Radiología/normas , Planificación de la Radioterapia Asistida por Computador/normas , Neoplasias de la Vejiga Urinaria/radioterapia , Humanos , Estudios Prospectivos , Oncología por Radiación/normas , Tomografía Computarizada por Rayos X , Neoplasias de la Vejiga Urinaria/diagnóstico por imagen , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
PURPOSE: To describe and quantify bladder movement during radical radiation therapy (RT). To attempt to identify factors that predict for excessive alterations in bladder position. To use the above information to assist in defining the "adequate" planning target volume margin. METHODS AND MATERIALS: Thirty patients with bladder cancer suitable for radical courses of RT were followed prospectively. Patients had an initial planning computerized tomography (CT) scan of the pelvis and three subsequent scans performed weekly during the treatment period. The following measurements were made on each scan in the midbladder slice: maximum anteroposterior (AP) and lateral bladder dimensions, AP rectal diameter, and the distance (margin) between the bladder walls (anterior, posterior, right, and left lateral) and the 95% isodose line. Various patient and tumor data, including bladder and bowel symptoms, were recorded to attempt correlation with bladder movement. RESULTS: Bladder size: the median bladder size (area) over all scans in all patients was 36.9 cm2 (range: 16.2 to 80.9 cm2). The change in bladder area across each sequence varied from 3.3 to 29.1 cm2 (7-55% change in area between scans). Patients with bladders of larger than the median size on the planning scan (despite emptying) were more likely to have alteration in size than those with small bladders, and this change was in the direction of contraction (p = 0.01). Bladder displacement: bladder wall movement of > 1.5 cm was defined as "significant." Eighteen of 30 patients (60%) demonstrated "significant" movement of at least one bladder wall relative to the original isodose plot. Movement resulting in margin reduction occurred in 10 patients (33%). Two patients required treatment replanning due to consistently altered bladder position. There was no pattern to displacement through RT, and all walls were at approximately equal risk of movement. Factors influencing bladder movement: posterior bladder wall movement appeared to relate to "marked" (>2 cm) rectal diameter change. There was a trend for patients with larger amounts of residual bladder tumor (greater than the median) to exhibit more bladder movement; 11 of 14 "moved" compared with 7 of 16 patients with less residual tumor. Other clinical factors including age, sex, body size, acute RT reaction, and tumor stage did not appear to relate to bladder movement. CONCLUSION: Bladder movement during RT is clinically relevant and is random with respect to both time and direction. We recommend, at least with respect to tumor-bearing regions of the bladder, that no less than a 2.0 cm margin should be allowed.
Asunto(s)
Movimiento , Planificación de la Radioterapia Asistida por Computador/métodos , Vejiga Urinaria/diagnóstico por imagen , Anciano , Femenino , Humanos , Masculino , Estudios Prospectivos , Recto/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Vejiga Urinaria/patologíaRESUMEN
It has been shown that radioactive material can be localized to lymphocyte traffic areas using radiolabeled autologous lymphocytes and that 114mIn deposited in such a way in rats produces a lymphopoenia by establishing a selective internal irradiation of circulating lymphocytes. The study reported here was undertaken to investigate the feasibility of using this technique in patients with lymphoid cell malignancy. Up to 22.7 MBq was administered to seven patients with active non-Hodgkin's lymphoma involving the spleen and the behavior of the radioactive material was followed over subsequent months. Estimates of the activity in peripheral blood, bone marrow, excreta samples, and of the variation in the whole-body distribution were obtained. The administered radioactive material cleared rapidly from the blood, 85% being removed within the first 30 min. There was an almost immediate uptake of most of this by the spleen and liver with less than 5% of administered activity accumulating in the bone marrow. After 48 hr, the whole-body distribution changed only slowly and there was a regular decrease of the activity in the spleen. Excretion of radioactive material occurred via both the urine and feces and amounted to less than 1% of administered activity per day. This pharmacokinetic data was used to calculate radiation absorbed doses to various organs for a standard man. It is concluded that this represents a feasible technique for the targeting of radioactive material for the treatment of lymphoid malignancy.
Asunto(s)
Radioisótopos de Indio/uso terapéutico , Linfocitos , Linfoma no Hodgkin/radioterapia , Adulto , Anciano , Recuento de Células Sanguíneas , Médula Ósea/efectos de la radiación , Femenino , Humanos , Linfocitos/efectos de la radiación , Linfoma no Hodgkin/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Cintigrafía , Dosificación Radioterapéutica , Bazo/efectos de la radiación , Recuento Corporal TotalRESUMEN
The synthetic steroid methyltrienolone (R1881, 17beta-hydroxy-17alpha-methyl-estra-4,9,11-trien-3-one) binds with high affinity to protein in cytosols prepared from human hyperplastic prostate. R1881 also binds to the androgen receptor of rat prostate and the progesterone receptor of rabbit uterus. Other steroids compete with R1881 for unoccupied binding sites in the human prostatic cytosols in a manner similar to that observed with the rabbit uterine progesterone receptor, rather than the rat prostatic androgen receptor. The progesterone receptor-like binding sites are a feature of the prostatic stroma rather than the epithelium.
Asunto(s)
Citosol/metabolismo , Estrenos/metabolismo , Próstata/metabolismo , Receptores de Progesterona , Congéneres de la Testosterona/metabolismo , Animales , Unión Competitiva , Femenino , Humanos , Masculino , Próstata/ultraestructura , Conejos , Ratas , Receptores Androgénicos , Útero/metabolismoRESUMEN
Sex hormone-binding globulin-(SHBG) and cortisol-binding globulin-(CBG) like proteins have been demonstrated in prostatic tissue surgically removed from patients with benign prostatic hyperplasia. These proteins are not easily removed by superfusion of tissue slices. Epithelial tissue was separated from stroma and found not to contain the SHBG- or CBG-like proteins. Substantial amounts of these proteins, however, remained associated with the stroma. It is suggested that they may be constituents of interstitial fluid in this tissue compartment. The possible significance of this in benign prostatic hyperplasia is discussed.
Asunto(s)
Próstata/metabolismo , Hiperplasia Prostática/metabolismo , Globulina de Unión a Hormona Sexual/metabolismo , Transcortina/metabolismo , Sitios de Unión , Separación Celular/métodos , Citosol/análisis , Dihidrotestosterona/metabolismo , Humanos , Hidrocortisona/metabolismo , MasculinoRESUMEN
Using arginase and hydroxyproline as biochemical markers, the yields and homogeneity of separated epithelial and stromal tissues from surgically removed benign hyperplastic prostate glands have been assessed. On the basis of these markers, about 30% of epithelial and 95% of stromal tissues were recovered. Dehydroepiandrosterone sulphate sulphatase activity was found predominantly in the epithelium, whereas testosterone 5alpha-reductase activity was predominantly in the stroma.
Asunto(s)
Hiperplasia Prostática/enzimología , 3-Oxo-5-alfa-Esteroide 4-Deshidrogenasa/metabolismo , Anciano , Arginasa/metabolismo , Separación Celular , Deshidroepiandrosterona , Células Epiteliales , Epitelio/enzimología , Humanos , Hidroxiprolina/metabolismo , Masculino , Persona de Mediana Edad , Sulfatasas/metabolismoRESUMEN
Six male volunteers were infused with arginine (0.5 g/kg body weight) over 30 min, after an overnight fast and water deprivation. There was a significant decrease in renal phosphate clearance (P less than 0.025) and urinary cyclic adenosine monophosphate (cAMP) output (P less than 0.025) during the 60- to 90-min period after the beginning of the infusion; both returned to the preinfusion basal levels within 150 min. The plasma levels of parathyroid hormone (PTH) were not affected by the infusion and remained unchanged during the subsequent 150 min. Plasma levels of arginine vasopressin (AVP) were also not significantly affected although plasma osmolality increased by 6-9 mmol/kg in all subjects. The infusion resulted in a diuresis, and a fall in urine osmolality but a decrease in free-water clearance; creatinine clearance was not affected. Six other subjects were given a bolus of 230 i.u. PTH intravenously, and 20 days later this was repeated during an infusion of arginine (0.5 g/kg body weight). There was a significant decrease in urinary phosphate (P less than 0.025) and cAMP excretion (P less than 0.05) when PTH was given with arginine. It is suggested that arginine blocks the action of PTH on the proximal renal tubule but not that of vasopressin on the distal nephron and collecting ducts.
Asunto(s)
Arginina Vasopresina/fisiología , Arginina/farmacología , Túbulos Renales/fisiología , Hormona Paratiroidea/fisiología , Agua Corporal/metabolismo , Creatinina/metabolismo , AMP Cíclico/orina , Humanos , Masculino , Concentración Osmolar , Fosfatos/metabolismo , Sodio/sangreRESUMEN
BACKGROUND AND PURPOSE: The treatment of elderly patients with high or intermediate grade non-Hodgkin's lymphoma (NHL) remains difficult and controversial. In order to audit our own practice, 270 elderly patients treated between 1988 and 1993 with this diagnosis were retrospectively reviewed. MATERIAL AND METHODS: 81 patients unfit for chemotherapy received fractionated radiotherapy for apparently localised stage I or II disease. The median age of the patients was 78 years (range 70-87 years). Forty stage I and 17 stage II patients had extra-nodal sites of disease. The radiation field included the primary site plus immediate adjacent nodes. RESULTS: After a median follow-up of 3.9 years the 5-year overall and disease-free survival rates were 33% and 31%, respectively. Age (hazard ratio (HR) 1.22, P = 0.03), stage (HR 5.50, P = 0.02) and lactate dehydrogenase level (HR 1.003, P = 0.004) were identified as independent risk factors for relapse. CONCLUSION: These factors can define a group in which radiotherapy can produce acceptable survival rates (age < or = 80 years, stage I and lactate dehydrogenase < or = 500). This group represented 34% of those patients where all these variables were recorded and had 5-year disease-free and overall survival rates of 56% and 62%, respectively.
Asunto(s)
Linfoma no Hodgkin/radioterapia , Factores de Edad , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Humanos , Linfoma no Hodgkin/mortalidad , Masculino , Tasa de SupervivenciaRESUMEN
The acute effects of a single intravenous injection of 2 micrograms of 1 alpha-hydroxycholecalciferol (alfacalcidol) were studied for a 24-h period in six normal males (mean age 33 years), six women with primary hyperparathyroidism (mean age 72 years) and six women with established osteoporosis (mean age 63 years). In all three groups, serum calcitriol levels rose to a peak 2-3 h after administration of alfacalcidol. Basal levels were highest in the primary hyperparathyroidism group at (mean +/- SEM) 81 +/- 2 vs 62 +/- 12 (normal males) (p < 0.05) and 56 +/- 5 pmol/l (osteoporosis) (p < 0.01). Highest peak levels were found also in the primary hyperparathyroidism group at 150 +/- 15 vs 114 +/- 15 (normal males) (p < 0.05) and 127 +/- 15 pmol/l (osteoporosis) (p < 0.01). The rise in calcitriol was higher in the primary hyperparathyroidism group than either the normal males or osteoporotic patients (p < 0.05). No significant differences were evident in basal serum calcidiol concentrations among the three treatment groups. As might be expected, highest basal concentrations of parathyroid hormone (PTH), serum calcium and serum osteocalcin were noted in the primary hyperparathyroid group (PTH: 17.1 +/- 7.7 vs 1.9 +/- 0.5 (normal males) (p < 0.01) and 2.1 +/- 0.3 pmol/l (osteoporosis) (p < 0.01); calcium: 3.06 +/- 0.08 vs 2.50 +/- 0.02 (normal males) (p < 0.01) and 2.43 +/- 0.02 mmol/l (osteoporosis) (p < 0.01); osteocalcin: 1.10 +/- 0.08 vs 0.56 +/- 0.16 (normal males) (p < 0.05) and 0.53 +/- 0.21 nmol/l (osteoporosis) (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Calcitriol/sangre , Hidroxicolecalciferoles/farmacología , Osteocalcina/sangre , Hormona Paratiroidea/sangre , Adulto , Anciano , Fosfatasa Alcalina/sangre , Análisis de Varianza , Calcio/sangre , Femenino , Humanos , Hidroxicolecalciferoles/administración & dosificación , Hiperparatiroidismo/sangre , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Osteoporosis Posmenopáusica/sangreRESUMEN
The relation between urinary sodium excretion (NaE) and renal tubular calcium reabsorption (TmCa/GFR) was assessed in patients with hypercalcaemia associated with malignancy and primary hyperparathyroidism. On acute saline loading of seven normally hydrated patients with primary hyperparathyroidism and five patients with malignancy, raised values of TmCa/GFR were reduced to normal in most cases, in association with increases in NaE. The reduction in TmCa/GFR, which occurred, may have been due to a reduction in proximal tubular calcium reabsorption associated with sodium: this would have obscured the effect of humorally mediated increases in distal tubular calcium reabsorption, which are stimulated either by parathyroid hormone or by a putative humoral mediator in hypercalcaemia of malignancy. In patients who were normally hydrated NaE and TmCa/GFR were not significantly correlated. When data were included from patients who were dehydrated and from those undergoing acute saline loading, significant inverse correlations between NaE and TmCa/GFR were observed both in primary hyperparathyroidism (r = -0.49; p less than 0.02) and malignancy (r = -0.60; p less than 0.001). In clinical practice changes in TmCa/GFR associated with sodium seem to be of minor importance under normal circumstances, but they become evident at the upper and lower extremes of urinary sodium excretion. In clinical studies of renal calcium handling urinary sodium excretion must also be assessed, as interpreting TmCa/GFR data is difficult in states of excessive sodium loading or depletion.