RESUMEN
Cisplatin-induced toxicities are mainly caused by the formation of free radicals, leading to oxidative organ damage. Plasma concentrations of antioxidants decrease significantly during cisplatin chemotherapy for cancer. Forty-eight cancer patients treated with cisplatin-based chemotherapy were randomised in a double-blind manner to receive either supplementation with vitamin C, vitamin E and selenium dissolved in a beverage or to receive a placebo beverage. Primary outcome measures were the amount of nephrotoxicity and ototoxicity induced by cisplatin. No significant differences were found between the two study groups with respect to these primary outcome measures. However, patients who achieved the highest plasma concentrations of the three antioxidant micronutrients had significantly less loss of high-tone hearing. In addition, significant correlations were found between the reduced/oxidised vitamin C ratio and malondialdehyde (MDA), markers of oxidative stress, and cisplatin-induced ototoxicity and nephrotoxicity. The lack of protection against cisplatin-induced toxicities in patients in the intervention arm may be related to poor compliance and/or inadequate supplementation. Supplementation with a higher dose (intensity) and in combination with other antioxidants should be investigated further.
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Antineoplásicos/efectos adversos , Antioxidantes/administración & dosificación , Cisplatino/efectos adversos , Suplementos Dietéticos , Micronutrientes/administración & dosificación , Neoplasias/tratamiento farmacológico , Adolescente , Adulto , Anciano , Ácido Ascórbico/administración & dosificación , Ácido Ascórbico/sangre , Cisplatino/administración & dosificación , Método Doble Ciego , Femenino , Humanos , Masculino , Malondialdehído/sangre , Persona de Mediana Edad , Selenio/administración & dosificación , Selenio/sangre , Vitamina E/administración & dosificación , Vitamina E/sangreRESUMEN
Over the past decades, Positron Emission Tomography has opened a new field of imaging. Nowadays, this technique is being used for diagnosing, staging disease as well as for prognostic stratification and monitoring therapy. In this respect, [18F]fluorodeoxyglucose (FdGlc) is by far the most commonly used PET agent. Many factors have been identified being responsible for a high uptake of this agent in malignancy. However, additional factors such as tumour treatment may interfere with the uptake mechanism. Knowledge of all these factors is a prerequisite for an optimal interpretation of PET studies and, consequently, for a reliable judgement of tumour status. In this article, a review is given of the factors influencing FdGlc uptake and the implications for clinical studies.
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Fluorodesoxiglucosa F18/metabolismo , Radiofármacos/metabolismo , Tomografía Computarizada de Emisión , Ciclo del Ácido Cítrico , Regulación Enzimológica de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Glucólisis , Hexoquinasa/metabolismo , Humanos , Mitocondrias/metabolismo , Proteínas de Transporte de Monosacáridos/metabolismo , Neoplasias/metabolismo , Tomografía Computarizada de Emisión/métodos , Regulación hacia ArribaRESUMEN
PURPOSE: To evaluate the risk of major thromboembolic complications in male germ cell cancer patients receiving cisplatin-based chemotherapy and to review the literature on this subject. PATIENTS AND METHODS: One hundred seventy-nine germ cell cancer patients treated between January 1979 and May 1997 in our hospital were analyzed with respect to risk factors for developing thromboembolic events, such as baseline tumor characteristics, prior tumor therapy, administration of cytostatic agents, and the use of antiemetic drugs. The patients were treated with a variety of combination chemotherapy regimens, primarily cisplatin-containing combination regimens. RESULTS: Of the 179 patients, 15 patients (8.4%) were identified who developed a total of 18 major thromboembolic complications in the time period between the start of chemotherapy and 6 weeks after administration of the last cytostatic drug in first-line treatment. Of these 18 events, three (16.7%) were arterial events, including two cerebral ischemic strokes, and 15 (83. 3%) were venous thromboembolic events, including 11 pulmonary embolisms. One (5.6%) of the 18 events was fatal. Liver metastases (odds ratio, 4.9; 95% confidence interval, 1.1 to 20.8) and the administration of high doses of corticosteroids (>/= 80 mg dexamethasone per cycle; odds ratio, 3.5; 95% confidence interval, 1. 2 to 10.3) as antiemetic therapy were identified as risk factors for the development of major thromboembolic complications. CONCLUSION: Germ cell cancer patients who receive chemotherapy, in particular those who have liver metastases or receive high doses of corticosteroids, are at considerable risk of developing thromboembolic complications.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cisplatino/efectos adversos , Germinoma/tratamiento farmacológico , Neoplasias Testiculares/tratamiento farmacológico , Tromboembolia/inducido químicamente , Bleomicina/efectos adversos , Estudios de Cohortes , Humanos , Incidencia , Modelos Logísticos , Masculino , Estudios Retrospectivos , Factores de Riesgo , Tromboembolia/epidemiologíaRESUMEN
Thirty-three metastatic melanoma patients were vaccinated according to a phase I-II study with an allogeneic melanoma cell line that was genetically modified by transfection with a plasmid containing the gene encoding human interleukin 2 (IL-2). The cell line expresses the major melanoma-associated antigens and the HLA class I alleles HLA-A1, -A2, -B8, and Cw7. All patients shared one or more HLA class I alleles with this cell line vaccine. Patients were immunized by three vaccinations, each consisting of 60 x 106 irradiated (100 Gy) melanoma cells (secreting 120 ng of IL-2/10(6) cells/24 hr) administered subcutaneously at weekly intervals for 3 consecutive weeks. Side effects of treatment consisted of swelling of locoregional lymph nodes and induration at the site of injection, i.e., a delayed-type hypersensitivity (DTH) reaction. In three patients, vaccination induced inflammatory responses in distant metastases containing necrosis or apoptosis along with T cell infiltration. Apoptosis occurred only in Bcl-2-negative areas, not in Bcl-2-expressing parts of the metastases. Two other patients experienced complete or partial regression of subcutaneous metastases. Seven patients had protracted stabilization (4 to >46 months) of soft tissue metastases, including one patient who developed vitiligo after vaccination. Immune responses to the vaccine could be detected in 67% of the 27 patients measured. Vaccination was shown to induce a variable change in the number of anti-vaccine cytotoxic T lymphocytes (CTLs) in peripheral blood, which did not correlate with response to treatment. However, in two of five patients the frequency of anti-autologous tumor CTLs measured was significantly higher than before vaccination. This study demonstrates the feasibility, safety, and therapeutic potential of vaccination of humans with allogeneic, gene-modified tumor cells, and that frequencies of vaccine-specific CTLs among patient lymphocytes can be determined by using a modified limited dilution analysis (LDA).
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Vacunas contra el Cáncer/farmacología , Interleucina-2/metabolismo , Melanoma/secundario , Melanoma/terapia , Adulto , Anciano , Antígenos de Neoplasias/genética , Vacunas contra el Cáncer/genética , Femenino , Antígeno HLA-A1/metabolismo , Antígeno HLA-A2/metabolismo , Antígeno HLA-B8/metabolismo , Antígenos HLA-C/metabolismo , Humanos , Inmunoterapia/métodos , Inflamación/inmunología , Interleucina-2/genética , Interleucina-2/farmacología , Antígeno MART-1 , Masculino , Melanoma/mortalidad , Antígenos Específicos del Melanoma , Persona de Mediana Edad , Monofenol Monooxigenasa/genética , Proteínas de Neoplasias/genética , Tasa de Supervivencia , Linfocitos T Citotóxicos/inmunología , Resultado del Tratamiento , Células Tumorales CultivadasRESUMEN
OBJECTIVE: To review the results 5 years after treatment of patients with testicular non-seminoma. DESIGN: Retrospective, descriptive. METHOD: The records were studied of the 146 patients treated in Leiden University Hospital, the Netherlands, in 1979-1993 for non-seminoma of the testicle. The median age was 27 years (range: 16-76). The median follow-up duration was 65 months (range: 4-172). The Kaplan-Meier method was used to calculate the recurrence and survival rates. RESULTS: In all, 21 of the 146 patients died (5-year survival rate: 84%). Five patients died as a result of treatment. A relapse occurred in 14 of the 49 stage I patients after frequent controls according to the European Organization for Research and Treatment of Cancer (EORTC) standards. One of these patients died after he refused further treatment for his relapse (5-year survival rate: 96%), 92 patients, including 13 from the stage I group, were treated according to protocol with chemotherapy because of metastatic disease, of whom 51 underwent surgery following primary treatment. The histology of the resected material showed vital tumour tissue in 14 of the 51 patients (27%). Seven patients never reached complete remission after chemotherapy and died. In 12 of the 92 patients a relapse occurred after chemotherapy; seven of these died despite further treatment. The 5-year survival rate of the 92 patients with metastatic disease was 82%. None of the surviving patients developed a second primary or major pulmonary, renal or auditory problem. CONCLUSION: The chance of cure and survival in patients suffering from testicular non-seminoma with the help of chemotherapy and surgery is over 80%. In stage I patients intensive surveillance, and chemotherapy in case of a relapse, is effective. Even patients with metastatic disease have a high probability of being cured with few long-term side effects.
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Germinoma/epidemiología , Germinoma/terapia , Neoplasias Testiculares/epidemiología , Neoplasias Testiculares/terapia , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Supervivencia sin Enfermedad , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Países Bajos/epidemiología , Orquiectomía , Pronóstico , Recurrencia , Inducción de Remisión , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: Antioxidants protect the body against cellular oxidative damage and thus some of the adverse effects induced by cisplatin and other cytostatic drugs. PATIENTS AND METHODS: The effect of cisplatin-combination chemotherapy on concentrations of plasma antioxidants was studied in 36 cancer patients, including osteosarcoma and testicular carcinoma patients. RESULTS: Eight to 15 days after the start of each cytostatic drug infusion concentrations of various plasma antioxidants were measured and compared to pretreatment values: vitamin C and E, uric acid and ceruloplasmin levels fell significantly (P < 0.01-0.005) and returned to baseline levels before the start of the next chemotherapy cycle. Levels of the antioxidants bilirubin albumin and the ratio vitamin E/cholesterol + triglycerides measured three weeks after the start of chemotherapy significantly decreased compared to pretreatment levels and remained low thereafter (P < 0.001-0.002). Dietary intake of antioxidants and anthropometric measurements, evaluated in 14 patients did not change during the whole treatment period. CONCLUSIONS: Cisplatin-combination chemotherapy induces a fall in plasma antioxidant levels, that may reflect a failure of the antioxidant defense mechanism against oxidative damage induced by commonly used anticancer drugs. This probably results from consumption of antioxidants caused by chemotherapy induced-oxidative stress as well as renal loss of water-soluble, small molecular weight antioxidants such as uric acid.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Antioxidantes/análisis , Cisplatino/efectos adversos , Neoplasias/tratamiento farmacológico , Adolescente , Adulto , Anciano , Antropometría , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ceruloplasmina/análisis , Cisplatino/administración & dosificación , Cobre/sangre , Dieta , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Pérdida Auditiva Sensorineural/inducido químicamente , Humanos , Riñón/efectos de los fármacos , Masculino , Persona de Mediana Edad , Neoplasias/sangre , Neoplasias/orina , Estrés Oxidativo , Vitaminas/sangre , beta Caroteno/sangreRESUMEN
The effect of pamidronate treatment on the first development of bone metastases was investigated in 124 patients with breast cancer, with either locally advanced disease (n = 33) or extraskeletal metastases (n = 91), but no bone metastases in a randomised, multicentre, open controlled study. Patients were assigned to treatment with oral pamidronate, 300 mg/day, (n = 65) or to a control group (n = 59). Tumour therapy was freely allowed. A first clinical event of skeletal morbidity occurred in 22% pamidronate and 20% control patients; unequivocal first radiological manifestation of bone metastases was found in 36% pamidronate and 27% control patients (n.s.). The actuarial risk of a first skeletal event was similar in both groups. Quality-of-life measurements of bone metastases-related aspects showed no differences between the two groups. 19 patients withdrew from the study because of gastrointestinal complaints attributed to pamidronate. We conclude that supportive oral pamidronate treatment (300 mg/day) does not prevent nor delay the development of bone metastases in breast cancer patients at risk.
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Neoplasias Óseas/prevención & control , Neoplasias Óseas/secundario , Neoplasias de la Mama/patología , Difosfonatos/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Óseas/diagnóstico , Femenino , Humanos , Persona de Mediana Edad , Pamidronato , Calidad de Vida , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
Somatostatin receptor scintigraphy (SRS) with the diethylenetriaminopentaacetic-acid-conjugated somatostatin analogue [111In-DTPA-D-Phe1] octreotide, also known as 111In-pentetreotide, is a new non-invasive modality for the evaluation of tumours that express receptors for somatostatin. These receptors are present on neuroendocrine and other tumours, including lymphomas and some breast cancers. In oncology SRS is a promising diagnostic tool for localizing primary tumours, staging, control and follow-up after therapy, and for identification of patients who may benefit from therapy with unlabelled octreotide or, in the future, with radiolabelled octreotide. In the past few years many small and large studies investigating various aspects of SRS have been reported. In this review the value of SRS in the management of individual tumour types is explored. For many tumours the best sensitivity in lesion detection is only achieved by very careful imaging after the administration of at least 200 MBq 111In-pentetreotide. On the basis of the current experience the main value of SRS in oncology is in the staging and evaluation of gastroenteropancreatic tumours, paragangliomas, small-cell lung cancer and lymphomas. Promising areas for SRS are the evaluation of breast cancer, non-medullary thyroid cancer and melanoma, and initial results with targeted radionuclide therapy using radiolabelled octreotide have been reported.
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Neoplasias/diagnóstico por imagen , Receptores de Somatotropina/análisis , Secuencia de Aminoácidos , Humanos , Radioisótopos de Indio , Datos de Secuencia Molecular , Neoplasias/ultraestructura , Octreótido/análogos & derivados , Ácido Pentético/análogos & derivados , CintigrafíaRESUMEN
We searched for criteria that could indicate breast cancer families with a high prior probability of being caused by the breast/ovarian cancer susceptibility locus BRCA1 on chromosome 17. To this end, we performed a linkage study with 59 consecutively collected Dutch breast cancer families, including 16 with at least one case of ovarian cancer. We used an intake cut-off of at least three first-degree relatives with breast and/or ovarian cancer at any age. Significant evidence for linkage was found only among the 13 breast cancer families with a mean age at diagnosis of less than 45 years. An unexpectedly low proportion of the breast-ovarian cancer families were estimated to be linked to BRCA1, which could be due to a founder effect in the Dutch population. Given the expected logistical problems in clinical management now that BRCA1 has been identified, we propose an interim period in which only families with a strong positive family history for early onset breast and/or ovarian cancer will be offered BRCA1 mutation testing.
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Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/genética , ADN de Neoplasias/análisis , Ligamiento Genético/genética , Proteínas de Neoplasias/genética , Factores de Transcripción/genética , Adulto , Edad de Inicio , Proteína BRCA1 , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama Masculina/epidemiología , Neoplasias de la Mama Masculina/genética , Cromosomas Humanos Par 17 , Análisis Mutacional de ADN , Femenino , Humanos , Escala de Lod , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Neoplasias Ováricas/epidemiología , Neoplasias Ováricas/genética , LinajeRESUMEN
Experimental and clinical studies on ifosfamide indicate that fractionated treatment regimens have a higher efficacy compared to a single short-term infusion. In addition, protracted continuous infusion, in general, is often less toxic without loss of antitumour activity. To study the toxicity of a 10-day continuous infusion at increasing dosages of ifosfamide and mesna, 24 patients with a variety of advanced cancers (colon 10, pancreas 5, adenocarcinoma with unknown primary 5, and 4 others) received a total of 60 cycles (range 1-6 cycles, median 2) at 3 to 4 week intervals. The ifosfamide and mesna doses ranged from 654 mg m-2 day-1 to 1562 mg m-2 day-1 for a total of ten doses. Twenty-two patients were chemotherapy-naive. Pharmacia-Deltec CADD-1 pumps and Port-a-Cath implantable venous access devices were used. The dose-limiting toxicity was leucopenia without thrombocytopenia. At a dose of 1300 mg m-2 day-1 in 30% of the cycles in 7 patients leucopenia of WHO grades 3 and 4 was observed, while at higher dosages this percentage increased to 73%. Haemoglobin values usually decreased during the infusion with a mean of 1 mmol/l (range 0.3-2.5 mmol/l), frequently with partial or full recovery by the next cycle. The next most disturbing side-effect was fatigue (50% of patients WHO grades 2 and 3), and nausea and vomiting requiring drug treatment in 75% of patients. Renal failure and haematuria did not occur. There were two catheter-related complications: thrombosis (1 patient) and mechanical obstruction (1 patient). One patient developed severe encephalopathy at day 6 (total dose 18 g ifosfamide) with complete recovery after cessation of the infusion. In summary, a tolerable ifosfamide dose using this regimen in this previously largely untreated patient group appears to be 1200-1300 mg m-2 day-1 for 10 days. Fatigue is a frequent complaint and might be explained as a kind of neurotoxicity. The treatment can be administered to outpatients.
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Ifosfamida/administración & dosificación , Neoplasias/tratamiento farmacológico , Adulto , Anciano , Médula Ósea/efectos de los fármacos , Humanos , Ifosfamida/efectos adversos , Infusiones Intravenosas , Persona de Mediana EdadAsunto(s)
Anticuerpos/administración & dosificación , Neoplasias/radioterapia , Radioinmunoterapia , Anticuerpos/inmunología , Anticuerpos/metabolismo , Ensayos Clínicos como Asunto , Humanos , Marcaje Isotópico/métodos , Leucemia/radioterapia , Linfoma/radioterapia , Neoplasias/diagnóstico por imagen , Neoplasias/metabolismo , CintigrafíaRESUMEN
In a retrospective study survival after hypercalcemia in breast cancer patients has been investigated. A group of 72 patients were treated with bisphosphonate APD [3-(amino-1,1-hydroxypropylidene)bisphosphonate] and third-generation amino-containing bisphosphonates between January 1980 and October 1992. A median survival of 4.5 months was found. In a multivariate analysis, four independent prognostic factors for survival have been found: the interval between first relapse and hypercalcemia, sites of metastases at the moment of hypercalcemia, primary treatment, and the level of serum alkaline phosphatase. Patients with a "flare" reaction on tamoxifen treatment and patients with a normal serum alkaline phosphatase level and bone metastases only had a prolonged survival. Hypercalcemia associated with visceral metastases carried a very poor prognosis. The level of serum calcium in this series of patients was no prognostic indicator for survival.
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Neoplasias de la Mama/mortalidad , Hipercalcemia/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/fisiopatología , Neoplasias de la Mama/terapia , Supervivencia sin Enfermedad , Femenino , Humanos , Hipercalcemia/complicaciones , Menopausia , Persona de Mediana Edad , Análisis Multivariante , Metástasis de la Neoplasia , Recurrencia , Análisis de Regresión , Estudios Retrospectivos , Tasa de Supervivencia , Factores de TiempoRESUMEN
PURPOSE: We investigated whether the association of interleukin-2 (IL-2) with hypothyroidism is related to the presence of thyroid autoantibodies, dose of IL-2, and clinical effectiveness of treatment, and reviewed the literature. PATIENTS AND METHODS: Sixteen cancer patients were treated with high-dose recombinant, continuous infusion IL-2 (18 x 10(6) IU/m2/d) and lymphokine-activated killer (LAK) cells. One patient previously treated for a toxic goiter with radioactive iodine was analyzed separately. Thyroid function and levels of thyroid antibodies were determined regularly. RESULTS: Seven of 15 patients (47%) became hypothyroid with high serum thyrotropin (TSH) levels within 60 to 120 days after the start of treatment; five responded favorably to treatment (one complete remission [CR], four partial remissions [PRs]), compared with none of the other eight patients. Two hypothyroid patients developed antimicrosomal antibodies (AMAs), one showed a further increase of antithyroglobulin antibodies (TgAbs), and six developed TgAbs. Only one of eight euthyroid patients developed slightly elevated TgAb levels. Development of hypothyroidism correlated significantly with a favorable response to treatment (r = .76, P = .001). The patient, treated with radioactive iodine, also became hypothyroid with high levels of TSH and development of AMAs and TgAbs. No difference was found between the hypothyroid and euthyroid patients in mean cumulative dose of IL-2 administered within the first 60 days or total treatment period, or with the relative dose-intensity. No other autoantibodies were found and patients had normal corticotropin (ACTH) stimulation tests. CONCLUSION: The likelihood of developing (transient) hypothyroidism is higher in patients who respond to IL-2 treatment. The development of antithyroid antibodies suggests that IL-2 treatment triggers autoreactive B-cell clones or that cellular and/or cytokine-mediated thyroid destruction leads to activation of autoreactive B-cell clones.
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Autoanticuerpos/sangre , Hipotiroidismo/inducido químicamente , Hipotiroidismo/inmunología , Interleucina-2/efectos adversos , Glándula Tiroides/inmunología , Adulto , Anciano , Carcinoma de Células Renales/secundario , Carcinoma de Células Renales/terapia , Femenino , Humanos , Interleucina-2/uso terapéutico , Neoplasias Renales/terapia , Células Asesinas Activadas por Linfocinas/trasplante , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , Hormonas Tiroideas/sangreRESUMEN
A cross-sectional study of reverse smoking and its association with pre-malignant and malignant lesions of the palate was conducted in the north coastal areas of Andhra Pradesh, India. A total of 480 randomly selected persons were interviewed. Information about smoking status, diet and access to mass media was obtained in each case and an examination of the oral cavity was performed. Reverse smoking of chutta was practised by 33% of the total rural population. The prevalence rate of all palatal lesions was 55%. The prevalence rates of the separate lesions: leukoplakia palatii, palatal keratosis and palatal cancer, were 9.8%, 18.1% and 1.9%, respectively. The presence of these (pre-)malignant lesions was strongly associated with reverse smoking and also associated with conventional chutta smoking. Reverse smoking induced significantly more lesions than conventional chutta smoking, and was a major determinant of subsequent palatal cancer: all 9 newly diagnosed palatal cancers were observed within the group of reverse smokers. There was an inverse relationship between the incidence of palatal lesions and vitamin A intake. The study of access to mass media indicated that the most favourable medium for promoting a prevention campaign would be the cinema.
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Neoplasias Palatinas/etiología , Lesiones Precancerosas/etiología , Fumar/efectos adversos , Factores de Edad , Estudios Transversales , Femenino , Humanos , India/epidemiología , Masculino , Neoplasias Palatinas/epidemiología , Neoplasias Palatinas/patología , Lesiones Precancerosas/epidemiología , Lesiones Precancerosas/patología , Prevalencia , Factores de Riesgo , Población Rural , Fumar/patologíaRESUMEN
We have performed linkage analysis with five markers for the chromosome region 17q12-q21 in 13 Dutch breast cancer kindreds in order to find support for the claim by Hall et al. that a gene in this region, termed "BRCA1," is associated with predisposition to early-onset familial breast cancer. This work is part of a collaborative study, the results of which are published elsewhere in this issue. Best evidence for linkage was observed with the marker CMM86 (D17S74) in pedigrees with an average age at onset of < or = 47 years (LOD score = 1.77 at 1% recombination). In one breast-ovarian cancer family with a high probability of being linked to 17q, we observed one putative recombinant between D17S250 and D17S579, which suggests that BRCA1 is proximal to D17S579.
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Neoplasias de la Mama/genética , Mapeo Cromosómico/métodos , Cromosomas Humanos Par 17 , Proto-Oncogenes , Adulto , ADN de Neoplasias/análisis , ADN Satélite/análisis , Salud de la Familia , Femenino , Ligamiento Genético , Marcadores Genéticos , Humanos , Escala de Lod , Masculino , Persona de Mediana Edad , Síndromes Neoplásicos Hereditarios/genética , Países Bajos , Neoplasias Ováricas/genética , Linaje , Polimorfismo de Longitud del Fragmento de RestricciónRESUMEN
PURPOSE: An open, randomized study was performed to assess the effects of supportive pamidronate treatment on morbidity from bone metastases in breast cancer patients. PATIENTS AND METHODS: Eighty-one pamidronate patients and 80 control patients were monitored for a median of 18 and 21 months, respectively, for events of skeletal morbidity and the radiologic course of metastatic bone disease. The oral pamidronate dose was 600 mg/d (high dose [HD]) during the earliest study years, then changed to 300 mg/d (low dose [LD]) because of gastrointestinal toxicity. Twenty-nine of 81 pamidronate (HD/LD) patients first received 600 mg/d and were then changed to 300 mg/d; 52 of 81 pamidronate LD patients received 300 mg/d throughout the study. Tumor treatment was unrestricted. RESULTS: An overall intent-to-treat analysis was performed. In the pamidronate group, the occurrence of hypercalcemia, severe bone pain, and symptomatic impending fractures decreased by 65%, 30%, and 50%, respectively; event-rates of systemic treatment and radiotherapy decreased by 35% (P < or = .02). The event-free period (EFP), radiologic course of disease, and survival did not improve. Subgroup analyses suggested a dose-dependent treatment effect. Compared with their controls, in pamidronate HD/LD patients, events occurred 60% to 90% less frequently (P < or = .03) and the EFP was prolonged (P = .002). In pamidronate LD patients, event-rates decreased by 15% to 45% (P < or = .04). Gastrointestinal toxicity of pamidronate caused a 23% drop-out rate, but other cancer-associated factors seemed to contribute to this toxicity. CONCLUSION: Pamidronate treatment of breast cancer patients efficaciously reduced skeletal morbidity. The effect appeared to be dose-dependent. Further research on dose and mode of treatment is mandatory.
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Neoplasias Óseas/tratamiento farmacológico , Neoplasias de la Mama/patología , Difosfonatos/uso terapéutico , Neoplasias Óseas/secundario , Difosfonatos/administración & dosificación , Difosfonatos/efectos adversos , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Persona de Mediana Edad , Análisis Multivariante , Cuidados Paliativos , Pamidronato , Calidad de Vida , Análisis de Regresión , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
BACKGROUND: Because of the relative rarity of breast cancer in males, data have not been sufficient to support a definitive analysis of pertinent prognostic factors. Remarkably, no studies of male patients with breast cancer have presented survival information based on the number of histologically positive axillary nodes, the most sensitive single indicator of prognosis in women with breast cancer. METHODS: In this study, the clinical course of breast cancer was documented for 335 male patients registered from 1965 through 1986. For patients to be eligible, diagnoses had to be made within 3 months of registration and the patients had to have histologic confirmation and receive part or all of their initial treatment at 1 of 11 cancer centers participating in the International Patient Data Exchange System. RESULTS: The survival rate at 10 years was 84% for patients with histologically negative nodes, 44% for those with one to three positive nodes, and 14% for the group with four or more histologically positive nodes. The survival rates at 5 years were 90%, 73%, and 55%, respectively. In a multivariable analysis, the risk of death due to breast cancer for a patient with four or more histologically positive nodes was 6.75 times that of a patient with negative nodes. CONCLUSIONS: The findings of the authors indicate the following: (1) The number of histologically positive axillary nodes and, to a lesser degree, tumor diameter are significant prognostic factors for breast cancer in male patients. (2) The prognosis of breast cancer is the same in male and female patients when compared on the basis of the number of histologically positive nodes.