RESUMEN
OBJECTIVE: To assess the efficacy and tolerability of localised radiotherapy for the treatment of bicalutamide ('Casodex''Casodex' is a trademark of the AstraZeneca group of companies.)-induced gynaecomastia and/or breast pain. METHODS: This open-label, non-comparative, multicentre study included 51 patients receiving bicalutamide 150 mg for the treatment of non-metastatic prostate cancer (T1b-T4, Nx, M0). Patients who developed symptomatic gynaecomastia and/or breast pain received two 6-Gy fractions of external-beam radiation to the breasts and were then assessed at two 3-monthly follow-up visits. RESULTS: 37/51 (72.5%) patients experienced gynaecomastia and 41/51 (80.4%) experienced breast pain, typically within the first 6 months. Twenty seven and 38 patients, respectively, went on to receive breast irradiation. Following radiotherapy, gynaecomastia improved or resolved in 7/27 (25.9%) and 2/27 (7.4%) cases, respectively, and breast pain improved or resolved in 12/38 (31.6%) and 3/38 (7.9%) cases, respectively. No change was observed in 7 patients (25.9%) with gynaecomastia and 12 patients (31.6%) with breast pain, while 9 patients (33.3%) and 8 patients (21.1%), respectively, worsened. Radiotherapy-related adverse events, reported by 18/41 (43.9%) patients, were generally mild and short lived (median duration approximately 5 weeks). CONCLUSIONS: Therapeutic radiotherapy, using two fractions of 6 Gy external-beam radiation to the male breast, improves the intensity of bicalutamide-induced gynaecomastia and/or breast pain in approximately one-third of patients. Adverse events were often mild and short lived.
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Adenocarcinoma/tratamiento farmacológico , Anilidas/efectos adversos , Antineoplásicos/efectos adversos , Mama/efectos de la radiación , Ginecomastia/radioterapia , Dolor/radioterapia , Neoplasias de la Próstata/tratamiento farmacológico , Adenocarcinoma/patología , Edad de Inicio , Anciano , Anciano de 80 o más Años , Anilidas/uso terapéutico , Antineoplásicos/uso terapéutico , Estudios de Seguimiento , Ginecomastia/inducido químicamente , Ginecomastia/epidemiología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Nitrilos , Dolor/inducido químicamente , Dolor/epidemiología , Neoplasias de la Próstata/patología , Estudios Retrospectivos , Compuestos de Tosilo , Resultado del TratamientoRESUMEN
The impact of bicalutamide (Casodex) monotherapy on bone mineral density (BMD) was investigated in patients with locally advanced prostate cancer. BMD was assessed after treatment with bicalutamide 150 mg daily ( n=21) or by medical castration (goserelin acetate 3.6 mg every 28 days) ( n=8) for a median of 287 weeks. In 38% of castration compared with 17% of bicalutamide patients, femoral neck Z-scores were < or =-1 SD of the reference value (accepted as a two to three times increased risk of fracture) and T-scores were < or =-2.5 SD (World Health Organization definition of osteoporosis in white females). Total hip Z-scores were < or =-1 in 43% of castration patients and 13% of bicalutamide patients. In 38% of patients, lumbar spine BMD was affected by degenerative disease. These preliminary data suggest that there may be an advantage in terms of BMD in using bicalutamide monotherapy compared with castration; a benefit confirmed in a recent prospective randomised study.
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Anilidas/uso terapéutico , Antineoplásicos/uso terapéutico , Densidad Ósea/efectos de los fármacos , Orquiectomía , Neoplasias de la Próstata/tratamiento farmacológico , Receptores Androgénicos/uso terapéutico , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Nitrilos , Compuestos de TosiloRESUMEN
Castration is the most widely used form of androgen ablation employed in the treatment of metastatic (M1) prostate cancer. Non-steroidal antiandrogen monotherapy is a potential alternative treatment option for men for whom castration is unacceptable or not indicated. Of the three non-steroidal antiandrogens, bicalutamide ('Casodex'), flutamide and nilutamide, only bicalutamide has been compared with castration in large, controlled, randomised, Phase III trials in M1 patients. A post-hoc analysis of these studies indicated that bicalutamide 150 mg/day monotherapy may be of benefit to M1 patients with a prostate specific antigen (PSA) level 400 ng/ml) may decide that quality of life and symptomatic benefits outweigh the slight survival disadvantage seen in clinical trials and opt for bicalutamide monotherapy as an alternative to castration.Prostate Cancer and Prostatic Diseases (2001) 4, 196-203.
RESUMEN
PURPOSE: Nonsteroidal antiandrogen monotherapy may be a treatment option for some patients with advanced prostate cancer. We report a survival and safety update from an analysis of 2 studies in which patients with nonmetastatic (M0) locally advanced disease were treated with either 150 mg. bicalutamide monotherapy or castration. MATERIALS AND METHODS: Data from 2 open label, multicenter studies of identical design were pooled according to protocol. Patients with stage T3/4 prostate cancer were randomized to receive 150 mg. bicalutamide daily or castration (orchiectomy or 3.6 mg. goserelin acetate every 28 days) in a 2:1 ratio. RESULTS: A total of 480 patients with locally advanced prostate cancer were randomized to treatment. After a median followup of 6.3 years mortality was 56%. There was no statistically significant difference between the 2 groups in overall survival (hazard ratio 1.05, upper 1-sided 95% confidence limit 1.31, p = 0.70) or time to progression (1.20, 1.45, p = 0.11). There were statistically significant benefits in the bicalutamide monotherapy group in the 2 quality of life parameters of sexual interest (p = 0.029) and physical capacity (p = 0.046). The highest incidences of adverse events were the pharmacological side effects of hot flashes in the castration group, and breast pain and gynecomastia in the bicalutamide group. The incidences of other types of adverse events were low. Bicalutamide was well tolerated, with few drug related withdrawals from study, and no new safety issues were identified during this longer followup. CONCLUSIONS: Monotherapy with 150 mg. bicalutamide is an attractive alternative to castration in patients with locally advanced prostate cancer for whom immediate hormone therapy is indicated.
Asunto(s)
Antagonistas de Andrógenos/uso terapéutico , Anilidas/uso terapéutico , Castración , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/cirugía , Progresión de la Enfermedad , Estudios de Seguimiento , Humanos , Masculino , Estudios Multicéntricos como Asunto , Nitrilos , Neoplasias de la Próstata/mortalidad , Ensayos Clínicos Controlados Aleatorios como Asunto , Análisis de Supervivencia , Compuestos de TosiloRESUMEN
OBJECTIVE: The aim of this study was to compare the effects of the nonsteroidal antiandrogen flutamide plus the LH-RH analogue goserelin acetate (combined androgen blockade [CAB]) with goserelin acetate alone in patients with advanced prostate cancer. The original analyses at 25 and 56 months of follow-up have been reported previously, and here we report the final survival analysis after 10 years of follow-up. METHODS: 589 patients with advanced prostate cancer (55% with metastatic [M1] and 45% with locally advanced [M0] disease) were randomized to receive goserelin acetate 3.6 mg either alone or in combination with flutamide (250 mg three times daily). RESULTS: A total of 583 patients were included in the analysis. There was a small, but nonsignificant, benefit for CAB compared with goserelin acetate alone in all patients with respect to survival (hazard ratio 0.88, 95% CI 0.73, 1.06). Subgroup analysis of M0 and M1 patients showed similar results (M0: hazard ratio 0.92, 95% CI 0.68, 1.25; M1: hazard ratio 0.85, 95% CI 0.66, 1. 08). The treatment effect was not significantly different for M0 and M1 patients (p = 0.685). CONCLUSIONS: In this large randomized trial containing significant numbers of M0 patients, after 10 years there was a small but nonsignificant benefit for CAB over castration alone.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/mortalidad , Anciano , Anciano de 80 o más Años , Antagonistas de Andrógenos/administración & dosificación , Antineoplásicos Hormonales/administración & dosificación , Flutamida/administración & dosificación , Flutamida/uso terapéutico , Estudios de Seguimiento , Goserelina/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias de la Próstata/patología , Tasa de SupervivenciaRESUMEN
Many men with early stage prostate cancer suffer relapse and/or die of their disease despite potentially curative surgery or radiotherapy. Early hormonal therapies are being combined with these local therapies, with the aim of facilitating local control and improving survival. In the surgical setting, neoadjuvant hormonal therapy reduces the rate of positive margins and extracapsular penetration, but most studies have failed to demonstrate an advantage with respect to biochemical progression. Further studies are needed to clarify the role of adjuvant therapy in surgical patients. In the radiotherapy setting, neoadjuvant hormonal therapy improves local control, although survival data is not available, and can be considered for stage T2b disease or higher. Adjuvant luteinizing hormone-releasing hormone (LH-RH) agonists improve both local control and survival after radiotherapy and should be offered to all patients. Currently, the LH-RH agonists are the drugs of choice for adjuvant therapy, whereas combined androgen blockade has generally been used as neoadjuvant therapy. Monotherapy with a nonsteroidal antiandrogen has considerable potential in both settings. Areas for future studies include appropriate endpoints for clinical studies, comparative drug efficacy and the effect of treatment on quality of life.
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Antagonistas de Andrógenos/uso terapéutico , Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Quimioterapia Adyuvante , Terapia Combinada , Humanos , Masculino , Planificación de Atención al Paciente , Selección de Paciente , Pronóstico , Prostatectomía , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/cirugíaRESUMEN
For advanced prostate cancer, the main hormone treatment against which other treatments are assessed is surgical castration. It is simple, safe and effective, however it is not acceptable to all patients. Medical castration by means of luteinizing hormone-releasing hormone (LH-RH) analogues such as goserelin acetate provides an alternative to surgical castration. Diethylstilboestrol, previously the only non-surgical alternative to orchidectomy, is no longer routinely used. Castration reduces serum testosterone by around 90%, but does not affect androgen biosynthesis in the adrenal glands. Addition of an anti-androgen to medical or surgical castration blocks the effect of remaining testosterone on prostate cells and is termed combined androgen blockade (CAB). CAB has now been compared with castration alone (medical and surgical) in numerous clinical trials. Some trials show advantage of CAB over castration, whereas others report no significant difference. The author favours the view that CAB has an advantage over castration. No study has reported that CAB is less effective than castration. Of the anti-androgens which are available for use in CAB, bicalutamide may be associated with a lower incidence of side-effects compared with the other non-steroidal anti-androgens and, in common with nilutamide, has the advantage of once-daily dosing. Only one study has compared anti-androgens within CAB: bicalutamide plus LH-RH analogue and flutamide plus LH-RH analogue. At 160-week follow-up, the groups were equivalent in terms of survival and time to progression. However, bicalutamide caused significantly less diarrhoea than flutamide. Withdrawal and intermittent therapy with anti-androgens extend the range of treatment options.
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Antagonistas de Andrógenos/uso terapéutico , Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/cirugía , Antagonistas de Andrógenos/administración & dosificación , Antineoplásicos Hormonales/administración & dosificación , Humanos , Masculino , Orquiectomía , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
This paper reviews the aetiology, prevalence and treatment of gynaecomastia. Gynaecomastia is a proliferation of male breast tissue apparently caused by alterations in the ratio of oestrogen:androgen levels. It is common in the general population, resulting from normal physiological changes and various pathological causes. Gynaecomastia is also induced by many drug treatments, including hormonal therapies for prostate cancer. Prophylactic radiotherapy appears to be effective against gynaecomastia in this population. Surgery is an option for intractable cases, and some medical treatments have been reported, although there is a paucity of data evaluating such therapies.
RESUMEN
OBJECTIVES: To evaluate the efficacy and tolerability of 'Casodex' monotherapy (150 mg daily) for metastatic and locally advanced prostate cancer. METHODS: A total of 1,453 patients with either confirmed metastatic disease (M1), or T3/T4 non-metastatic disease with elevated prostate-specific antigen (M0) were recruited into one of two identical, multicentre, randomised studies to compare 'Casodex' 150 mg/day with castration. The protocols allowed for combined analysis. RESULTS: At a median follow-up period of approximately 100 weeks for both studies, 'Casodex' 150 mg was found to be less effective than castration in patients with metastatic disease (M1) at entry (hazard ratio of 1.30 for time to death) with a difference in median survival of 6 weeks. In symptomatic M1 patients, 'Casodex' was associated with a statistically significant improvement in subjective response (70%) compared with castration (58%). Analysis of a validated quality-of-life questionnaire proved an advantage for 'Casodex' in sexual interest and physical capacity. 'Casodex' had a substantially lower incidence of hot flushes compared to castration (6-13% compared with 39-44%) and the most commonly reported adverse events were those expected for a potent antiandrogen. However, in patients with M0 disease at entry, the data are still immature with only 13% of M0 patients having died. An initial analysis of this immature data has suggested that the results in these patients may be different to those obtained in patients with M1 disease. A further survival analysis in patients with M0 disease is therefore planned when the data are more mature. CONCLUSIONS: 'Casodex' 150 mg is less effective than castration in patients with M1 disease. However, 'Casodex' has shown a benefit in terms of quality of life and subjective response when compared to castration and has an acceptable tolerability profile. Thus 'Casodex' 150 mg monotherapy is an option for patients with M1 prostate cancer for whom surgical or medical castration is not indicated or is not acceptable.
Asunto(s)
Antagonistas de Andrógenos/uso terapéutico , Anilidas/uso terapéutico , Castración , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/cirugía , Anciano , Anciano de 80 o más Años , Antagonistas de Andrógenos/efectos adversos , Anilidas/efectos adversos , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/secundario , Castración/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Nitrilos , Probabilidad , Pronóstico , Antígeno Prostático Específico/análisis , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/mortalidad , Calidad de Vida , Tasa de Supervivencia , Compuestos de Tosilo , Resultado del TratamientoRESUMEN
OBJECTIVES: To compare the efficacy, tolerability, and quality of life benefits of bicalutamide (Casodex) 150-mg/day monotherapy and castration in previously untreated nonmetastatic (M0) advanced prostate cancer. METHODS: A total of 480 patients with Stage T3/T4 nonmetastatic disease randomly received oral bicalutamide 150 mg/day or castration (either bilateral orchiectomy or goserelin acetate [Zoladex] 3.6 mg every 28 days) in a 2:1 ratio in two open multicenter studies (studies 306 and 307). The design of these studies was similar to allow a pooled analysis. RESULTS: In the combined survival analysis, at median follow-up of 202 and 205 weeks in studies 306 and 307, respectively, with 31% of the cases resulting in death, bicalutamide 150-mg monotherapy was statistically equivalent to castration; the risk of death from any cause was 7% less with bicalutamide than with castration (hazard ratio [HR] = 0.93). Data on time to treatment failure and objective progression could not be pooled, as results for these end points differed between the trials. In study 306, bicalutamide 150-mg monotherapy increased time to objective progression (HR = 0.58; P = 0.033) and treatment failure (HR = 0.66; P = 0.074), whereas in study 307, time to progression (HR = 1.35; P = 0.0471) and treatment failure (HR = 1.24; P = 0.097) favored castration. Bicalutamide therapy showed significant advantages over castration for both sexual interest (P = 0.029) and physical capacity (P = 0.046). Bicalutamide 150-mg monotherapy was well tolerated. CONCLUSIONS: Bicalutamide 150-mg monotherapy provides a similar survival outcome to castration in previously untreated patients with nonmetastatic advanced prostate cancer and confers statistically significant benefits over castration with respect to sexual interest and physical capacity.
Asunto(s)
Antagonistas de Andrógenos/administración & dosificación , Anilidas/administración & dosificación , Antineoplásicos Hormonales/uso terapéutico , Castración , Goserelina/uso terapéutico , Neoplasias de la Próstata/terapia , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Método Doble Ciego , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Nitrilos , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/patología , Calidad de Vida , Tasa de Supervivencia , Factores de Tiempo , Compuestos de TosiloRESUMEN
OBJECTIVES: To evaluate the efficacy, tolerability, endocrinological effects and the pharmacokinetics of Casodex, when given as monotherapy during daily dosing of 10-200 mg to patients with advanced prostate cancer. METHODS: A total of 390 patients with advanced prostate cancer were treated for a minimum of 12 weeks with a daily monotherapy dose of Casodex. The doses ranged from 10 to 200 mg. Objective assessments of efficacy included: review of measurable metastases, prostate dimension, prostatic acid phosphatase and prostate-specific antigen (PSA) levels. Subjective assessments of efficacy included review of urological symptoms, performance status, bone scan and analgesic requirement. Pharmacokinetic samples were taken at various time points up to 3 months, and assayed using an achiral HPLC method. RESULTS: Clear objective responses were observed, particularly at doses of 50 mg and above. Specifically, the median percentage decrease in PSA at 50 mg was 90.0%, and at 100 and 200 mg it was 93.4 and 94.8%, respectively. Up to 53% of symptomatic patients demonstrated a subjective response at 3 months. Casodex was well tolerated at all doses with no effect on haematological or cardiovascular parameters and no effect on renal function. The expected pharmacological effects of potent antiandrogen therapy, such as breast tenderness (58%), gynaecomastia (48%), and hot flushes (17%), were reported, but these incidences reflected the direct eliciting of these events. The intrinsic efficacy of Casodex was demonstrated despite increases of 60% in testosterone levels. However, this increase reached a plateau after 4-12 weeks of therapy, but the majority of values remained within the normal range. Casodex has a half-life of approximately 1 week, enabling once-daily dosing with no effect of age or renal impairment on its pharmacokinetics. CONCLUSION: Casodex has a favourable side effect profile compared with the known safety profiles of other antiandrogens and has demonstrated intrinsic efficacy. Casodex warrants further investigation as a monotherapy for the management of advanced prostate cancer.
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Antagonistas de Andrógenos/uso terapéutico , Anilidas/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Fosfatasa Ácida/sangre , Antagonistas de Andrógenos/farmacocinética , Anilidas/administración & dosificación , Anilidas/farmacocinética , Antineoplásicos/farmacocinética , Relación Dosis-Respuesta a Droga , Estradiol/sangre , Hormona Folículo Estimulante/sangre , Humanos , Pruebas de Función Hepática , Hormona Luteinizante/sangre , Masculino , Invasividad Neoplásica/patología , Metástasis de la Neoplasia , Estadificación de Neoplasias , Nitrilos , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/patología , Testosterona/sangre , Compuestos de TosiloRESUMEN
Trilostane and aminoglutethimide, both given with a physiological replacement dose of hydrocortisone, were randomly allocated to 112 eligible patients with postmenopausal advanced breast cancer. Following treatment failure on either drug the patient continued with the other, if they were in a suitable clinical condition. Sixty-three patients initially received trilostane, of whom 33 subsequently received aminoglutethimide; 49 patients initially had aminoglutethimide and 14 of these then received trilostane. Both groups of patients were comparable in all respects. There was no difference in the response rate to either drug or in the average time to disease progression for the two drugs. Of the 47 patients who received both drugs, nine (19%) showed a response to both, indicating no cross-resistance. Side effects were seen to both drugs in approximately half the patients; these were mainly gastrointestinal symptoms with trilostane and rashes and drowsiness with aminoglutethimide. There was no evidence of cross-over patient susceptibility to side effects.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Administración Oral , Anciano , Aminoglutetimida/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/patología , Estudios Cruzados , Dihidrotestosterona/administración & dosificación , Dihidrotestosterona/análogos & derivados , Esquema de Medicación , Femenino , Humanos , Persona de Mediana Edad , Posmenopausia , Resultado del TratamientoRESUMEN
Casodex (Bicalutamide, ICI 176,334) is a potent, non-steroidal, selective anti-androgen with a long half-life allowing once-daily oral administration. In this randomised, open, multicentre study, Casodex 50 mg monotherapy was compared with castration (medical, using goserelin acetate, [Zoladex], or surgical) in 245 patients with advanced prostate cancer. Primary end-points were time to treatment failure, time to objective progression and survival. Subjective responses, quality of life and tolerability were also evaluated. There was no significant difference between the groups in terms of objective progression or subjective responses. Treatment failed in 59 of 119 patients (50%) randomised to Casodex and in 61 of 126 patients (48%) randomised to castration (no statistically significant difference). An updated analysis showed that survival was similar in the two groups. Casodex was well tolerated with a low incidence of diarrhoea and sexual dysfunction. On the basis of this study, Casodex monotherapy is an effective alternative to castration in the treatment of metastatic prostate cancer.
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Antagonistas de Andrógenos/uso terapéutico , Anilidas/uso terapéutico , Antineoplásicos/uso terapéutico , Carcinoma/secundario , Carcinoma/terapia , Orquiectomía , Neoplasias de la Próstata/patología , Anciano , Terapia Combinada , Humanos , Masculino , Nitrilos , Compuestos de Tosilo , Insuficiencia del TratamientoRESUMEN
Thirty-four evaluable patients were treated with vinorelbine, a novel, semisynthetic vinca alkaloid, as first-line chemotherapy for advanced breast cancer. They received vinorelbine 25 mg m-2 i.v. given weekly for a maximum of 16 cycles. Two patients achieved a complete remission and 15 a partial remission, giving a response rate of 17/34 (50%; 95% CI of 34-66%); median response duration was 5.8 months. The median progression-free interval was 4.4 months and median survival 9.9 months. Treatment was generally well tolerated. Fatigue was the most common side-effect. The main reason for dose adjustments was myelosuppression; 68% of patients had WHO grade 3 or 4 neutropenia and there was one death attributed to neutropenic sepsis. Nausea/vomiting and neuropathy were mild and alopecia was uncommon. This study confirms vinorelbine as a highly active, well-tolerated agent in advanced breast cancer worthy of evaluation in combination chemotherapy regimens.
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Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Vinblastina/análogos & derivados , Adulto , Anciano , Antineoplásicos/efectos adversos , Neoplasias de la Mama Masculina/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Vinblastina/efectos adversos , Vinblastina/uso terapéutico , VinorelbinaRESUMEN
Bone metastases are a common cause of morbidity in patients with breast cancer. In an open, phase II, non-comparative trial to investigate the effects of repeated infusions of pamidronate (Aredia) on pain, mobility, analgesic consumption, bone healing and bone metabolism, 69 patients with breast cancer and bone metastases received pamidronate 60 mg intravenously in 250 ml normal saline over 1 or 4 hours every 2 weeks for a total of 13 infusions, until either progressive disease or a serious adverse event. Improvement in pain score was seen in 33 of 54 evaluable patients (61%) as measured by a linear analogue pain scale, and in 28 of 56 evaluable patients (50%) as measured on a 6-point pain scale: 18 (30%) of 60 evaluable patients showed reduction in a 6-point analgesic score, while 28 patients (50%) showed some improvement in mobility, as assessed by a questionnaire. Sclerosis appeared in > 25% of bone lesions in 2 patients and in < 25% of bone lesions in 12 patients. Urinary calcium/creatinine ratios fell dramatically during therapy. One patient developed symptomatic hypocalcemia, 1 showed deterioration in pre-existing renal insufficiency. Fever occurred in 19% of patients, and less than 20% developed flu-like symptoms. We conclude that intravenous infusions of pamidronate at a dose of 60 mg every 2 weeks produces a marked reduction in pain in patients with extensive bone metastases from breast cancer.
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Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/secundario , Neoplasias de la Mama/tratamiento farmacológico , Difosfonatos/uso terapéutico , Cuidados Paliativos , Adulto , Anciano , Neoplasias de la Mama/patología , Difosfonatos/administración & dosificación , Difosfonatos/efectos adversos , Esquema de Medicación , Femenino , Humanos , Infusiones Intravenosas , Persona de Mediana Edad , Dimensión del Dolor , Pamidronato , Resultado del TratamientoRESUMEN
Alkylating agents have a well established role in the treatment of malignant disease, with well documented side effects. This case history, however, illustrates the susceptibility to these agents shown by some patients. It is suggested that, when drug induced pneumonitis is noted, careful screening of left ventricular function should be performed in order to diagnose myocardial fibrosis and subsequent cardiac failure.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Fibrosis Endomiocárdica/inducido químicamente , Enfermedades Pulmonares Intersticiales/inducido químicamente , Neoplasias de la Mama/tratamiento farmacológico , Quimioterapia Adyuvante , Resultado Fatal , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Primarias Múltiples/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Pericarditis Constrictiva/inducido químicamenteRESUMEN
Over 3,000 men, the majority of whom were patients with prostate cancer, were treated with Casodex (ICI 176,334), an oral anti-androgen, at doses ranging from 10 to 200 mg daily, corresponding to a total exposure to the drug of over 1,500 patient-years. Over this period, the tolerability of Casodex and its effect on quality of life were closely studied. Information on tolerability is presented from three large randomized trials of Casodex, 50 mg/day, in patients with prostate cancer, two large randomized trials of Casodex, 150 mg/day, in patients with prostate cancer and three double-blind, placebo-controlled trials of Casodex, 50 mg/day, in patients with benign prostatic hyperplasia (BPH). Information on quality of life and assessment of sexual functioning is presented from the trials using Casodex, 50 mg/day, for both prostate cancer and BPH. The most commonly reported adverse events were those that would be expected with an anti-androgen (i.e. breast tenderness, gynaecomastia and hot flushes). Overall, Casodex was well tolerated; there were no reports of light/dark adaptation problems or pulmonary fibrosis, and only one case of alcohol intolerance, which was not considered by the investigator to be treatment related. Only 0.3% of patients in the whole trial programme had to be withdrawn because of changes in liver function, and there were no clinically significant changes in mean liver function tests. Although there were no consistent differences between treatments for other aspects of quality of life, there was evidence of benefit from treatment with Casodex in maintaining both sexual interest and functioning.
Asunto(s)
Antagonistas de Andrógenos/uso terapéutico , Anilidas/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Calidad de Vida , Antagonistas de Andrógenos/administración & dosificación , Anilidas/administración & dosificación , Antineoplásicos/administración & dosificación , Método Doble Ciego , Humanos , Libido/efectos de los fármacos , Masculino , Nitrilos , Erección Peniana/efectos de los fármacos , Hiperplasia Prostática/tratamiento farmacológico , Compuestos de TosiloRESUMEN
In view of previous animal studies showing that pamidronate (Aredia) can cause renal damage, and human data indicating that pamidronate in doses of 60-90 mg is more effective in the control of tumor-induced hypercalcemia than when given at lower doses, we decided to investigate whether pamidronate 90 mg infused over 60 minutes at weekly intervals had any adverse effects on renal function in patients with bone metastases. Twelve patients, 7 female (all with breast cancer) and 5 male (4 with prostate cancer, 1 with bladder cancer) were entered into the trial. Each patient received weekly intravenous infusions of pamidronate 90 mg in 250 ml normal saline over 60 minutes for 4 weeks. 51Cr-EDTA clearances showed no significant changes in renal function. Urinary N-acetyl-B-D-glucosaminidase/creatinine ratios fluctuated considerably, but no consistent changes were found. No patient with a normal level of urinary beta 2-microglobulin had elevated levels at the end of the trial. Serum creatinine levels did not change significantly, though 1 patient had a corrected serum calcium level of < 2 mmol/L on a single occasion on day 8. No evidence of renal toxicity was detected. However, the possibility that neprohtoxicity would ultimately appear cannot be excluded, and these favourable short-term results cannot be extrapolated to patients with impaired renal function.
Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Difosfonatos/administración & dosificación , Riñón/efectos de los fármacos , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Adulto , Anciano , Creatinina/orina , Difosfonatos/efectos adversos , Difosfonatos/uso terapéutico , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Humanos , Infusiones Intravenosas , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , PamidronatoRESUMEN
Trilostane and Aminoglutethimide, each given with a physiological replacement dose of hydrocortisone, were randomly allocated to 72 eligible postmenopausal advanced breast cancer patients; following treatment failure on either drug the patient continued with the other drug, if in a suitable clinical condition. Thirty-eight patients initially received Trilostane of whom 19 subsequently received Aminoglutethimide; 34 patients initially had Aminoglutethimide and seven of these then received Trilostane. Both groups of patients were comparable in all respects. There was no difference in the objective response rate to either drug, Trilostane 11/38 = 29%, Aminoglutethimide 12/34 = 35%, nor in the average time to disease progression for the two drugs, Trilostane 64 weeks, Aminoglutethimide 68 weeks. Of the 26 patients who received both drugs, four showed a response to both suggesting no cross resistance. Side effects were seen to both drugs in approximately half of the patients, but were mainly gastro-intestinal with Trilostane and rash and drowsiness with Aminoglutethimide. There was no evidence of cross over patient susceptibility to side effects.