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Biomedical subjects

D Newling

Publications and source records attributed to D Newling.

At least 19 recordsLinked to original sources
PubMed2002

The management of localized prostate cancer.

At this point in time, the only possibility of curing prostate cancer is through the early detection and treatment of localized disease. The large number of treatment options available for localized prostate cancer, including radical prostatectomy, radiotherapy (either external beam or interstitial), hormone therapy and watchful waiting, can be confusing for the patient. These treatments are associated with different adverse effects, further complicating the treatment decision. As there will inevitably be a trade-off between expected cure and acceptable adverse effects, it is important to discuss all options with the patient. The doctor and patient must together decide the appropriate treatment for him and his tumor.

Aged↗
PubMed2001

Advanced prostate cancer: immediate or deferred hormone therapy?

The timing of hormone therapy in patients with advanced prostate cancer remains controversial. Although evidence from the Veterans Administration Cooperative Urological Group (VACURG) data indicated the potential benefit of immediate hormone treatment in terms of time to progression and disease-specific survival, it also supported the possibility of deferred treatment. This review looks at the results of subsequent studies of immediate versus deferred hormone therapy including the Medical Research Council (MRC) study, the European Organisation for Research and Treatment of Cancer (EORTC) studies, the Radiation Therapy Oncology Group (RTOG) study and the Eastern Cooperative Oncology Group (ECOG) study. Data from these studies and the availability of newer, better tolerated hormone therapies may well mean that the survival and welfare of patients with advanced prostate cancer could be considerably better with immediate hormone therapy rather than deferred treatment.

Antineoplastic Agents, Hormonal↗
PubMed1999

PIN I-III: when should we interfere?

The identification of 2 or 3 different grades of prostate intraepithelial neoplasia has led to a number of difficult concepts and treatment possibilities. Postmortem examination of the prostates of men over the age of 20, who have died of other causes, mainly road traffic accidents, have been examined and the earliest signs of intraepithelial neoplasia can be seen in some of them. The most common age for prostate cancer to present clinically is between 60 and 65 years and because the majority of men do not develop clinical prostate cancer, there must be a very large number who never progress further than PIN I or II. It is very rare for the early stages of intraepithelial neoplasia to be associated with frank carcinoma. However, it is known that PIN III is frequently found in the presence of carcinoma elsewhere in the gland and this stage is seen as a premalignant development. PIN III in the presence of prostate carcinoma is treated by whatever modality is used to treat the carcinoma. In the absence of carcinoma, there are urologists who consider that it should be regarded as a T1 tumor and radical prostatectomy or radiotherapy with delayed hormonal therapy are definite alternatives. From a certain amount of anecdotal evidence, it seems that the transition from PIN III to a focal carcinoma may take in the order of 2-3 years. Whether this transition can be definitely postponed by the early use of hormonal therapy is not known. Prostate intraepithelial neoplasia may also be treated by other modalities such as anti-angiogenesis agents, gene therapy, anti-metastatic agents, or metalloproteinase inhibitors. The effects of these treatments can be examined histologically by repeated biopsies to ensure that the process remains arrested. If the process of intraepithelial neoplasia can be identified at early stages, dietary modifications may well reduce mitogenic influences and slow down the process or even halt it altogether.

Biomarkers, Tumor↗
PubMed1998

Casodex 10-200 mg daily, used as monotherapy for the treatment of patients with advanced prostate cancer. An overview of the efficacy, tolerability and pharmacokinetics from three phase II dose-ranging studies. Casodex Study Group.

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.

Acid Phosphatase↗
PubMed1998

Maximal androgen blockade: final analysis of EORTC phase III trial 30853. EORTC Genito-Urinary Tract Cancer Cooperative Group and the EORTC Data Center.

OBJECTIVES: This prospective, randomized phase III study was initiated to compare the efficacy and side effects of bilateral orchiectomy versus a combination of a luteinizing hormone-releasing hormone agonist depot formulation, goserelin acetate (3.6 mg s.c. once every 4 weeks) and flutamide (250 mg 3 x daily) in patients with metastatic prostate cancer. METHODS: Relative treatment efficacy was assessed by comparing the two treatment groups with respect to response, time to first progression, progression-free survival, duration of survival and time to death due to malignant disease. RESULTS: There was a difference in response only with respect to a more frequent decrease to normal of the serum prostate acid phosphatase in patients assigned to maximal androgen blockade treatment. Additionally, maximal androgen blockade treatment showed significantly better results for duration of survival (p = 0.04), time to death due to malignant disease (p = 0.008), time to first progression (p = 0.009) and progression-free survival (p = 0.02). The most frequent side effects for both treatments included hot flushes and gynaecomastia. CONCLUSIONS: Increased time to progression and duration of survival is achieved by the combination of flutamide and goserelin when compared to bilateral orchiectomy.

Aged↗
PubMed1997

Assessment of hormone refractory prostate cancer.

OBJECTIVES: To define guidelines for the assessment of treatment in patients with hormone-refractory prostate cancer (HRPC). METHODS: In the light of modern research, and taking new treatment options into account, the Committee essays to specify different categories of patients entering clinical trials, and to define response criteria and those endpoints that are relevant in phase III studies and in short-term follow-up. RESULTS: HRPC comprises a range of disease states with varying responsiveness to therapy and length of survival. Patients with progression as evaluated by increasing prostate-specific antigen (PSA) values alone have a more favorable prognosis than those presenting with increasing tumor spread. In the assessment of these patients, the modes of previous therapy and the kind of tumor progression must be taken into account. The benefit of treatment of HRPC is often modest. While duration of survival remains the main and ultimate endpoint, the means of measuring short-term responsiveness to therapy are limited. A minority of patients have measurable tumor lesions. Decrease of PSA or other biochemical tumor markers may indicate depression of the tumor activity, but is not always associated with prolongation of survival. A variety of new treatments in HRPC are being investigated. They affect measurable tumor parameters in different ways. CONCLUSIONS: When a new agent is to be tested, it is important to measure all possible parameters before deciding which particular ones are appropriate for future investigations of this agent. In symptomatic patients, evaluation of subjective parameters, for example, relief of pain or improvement of performance status, is often the most reliable measure of treatment effect. However, these parameters should be clearly defined.

Antineoplastic Agents, Hormonal↗
PubMed1993

Orchidectomy versus goserelin plus flutamide in patients with metastatic prostate cancer (EORTC 30853). European Organization for Research and Treatment of Cancer--Genitourinary Group.

A total of 327 patients with metastatic prostate cancer were randomized to receive bilateral orchiectomy or treatment with Zoladex and flutamide. The trial aimed to evaluate subjective and objective time to progression, survival, and incidence and duration of response. Strict quality control and evaluation by independent ad hoc committees were organized. Progression was assessed for each of 13 parameters. The time to subjective and objective progression was in favor of the combination treatment, with statistical significances of P = 0.009 and P = 0.008, respectively. This delay in objective progression resulted in increased survival in favor of the combination treatment for death by cancer (P = 0.02) or overall survival (P = 0.05). Survival differences were more marked in the patients with better prognostic factors. The clinical significance of these differences for the individual patient requires detailed assessment.

Adult↗
PubMed1993

Goserelin acetate and flutamide versus bilateral orchiectomy: a phase III EORTC trial (30853). EORTC GU Group and EORTC Data Center.

Maximal androgen blockade (MAB), the eradication of the effects of adrenal androgens on prostate cancer cells after castration, has been used with differing success in the treatment of prostatic carcinoma. The aim of this randomized phase III study was to compare the efficacy and side effects of bilateral orchiectomy versus a combination of a luteinizing hormone-releasing hormone agonist (LHRH-A) depot formulation, goserelin acetate (3.6 mg s.c. once every four weeks), and flutamide (250 mg three times daily), in patients with metastatic cancer. Treatment usually continued until disease progression (or for a minimum of three months). Efficacy was assessed by response, time to disease progression, and duration of survival. Clinical evaluations, standard laboratory tests, and imaging examinations were carried out regularly. A total of 327 patients were entered in this study. There was a difference in response only for prostatic acid phosphatase (PAP) with a more frequent decrease of the serum values to normal in the serum in patients assigned to MAB treatment. The MAB treatment, however, proved significantly better for time to subjective progression, time to objective progression, time to first (subjective and objective) progression, and duration of survival. The most frequent side effects for both treatments included hot flushes and gynecomastia. In conclusion, significant time to progression and survival benefits are achieved by adding flutamide to an LHRH-A regimen, probably improving the quality of life of patients with metastatic cancer.

Aged↗
PubMed1991

Total androgen ablation: European experience. The EORTC GU Group.

Zoladex plus flutamide significantly delays the time to progression (subjective, objective, first progression) compared with orchiectomy, but no difference in survival (death from all causes or from malignant disease) could be detected. Thus, a delay in the appearance of progression has not improved survival. In fact, the duration of survival after progression tends to be shorter on Zoladex plus flutamide. There is thus no evidence to suggest any survival benefit with Zoladex plus flutamide. The quality control of our data revealed acknowledged problems in defining responses in patients with advanced prostate cancer. The review of the Bone Scan Committee provided the data for Tables 5 to 7. These data must provoke some reflections and emphasize once again the heterogeneity of the studied patient population. Table 4 on pain response after 4 weeks is just one of the many items to be analyzed by the committees for response criteria and quality of life. We expect that the other trials face similar problems. More work and patience are needed to obtain a firm answer to this clinical problem. These efforts will never be wasted, however, because the combined results of these trials will increase our knowledge of the treated history of prostate cancer and will, we hope, indicate a net treatment benefit in some subsets of patients. An individually tailored treatment for each patient selected from the anonymous mass of cases of advanced prostate cancer would be the highest reward of our continued collaboration with all the study groups.

Aged↗
PubMed1990

Orchidectomy versus Zoladex plus Eulexin in patients with metastatic prostate cancer (EORTC 30853).

A total of 327 patients with metastatic prostate cancer have been randomized to either orchidectomy or treatment with goserelin (Zoladez) 3.6 mg depot preparation combined with flutamide (Eulexin) 250 mg t.i.d. in a phase III study (EORTC 30853). A small but statistically significant difference in time to subjective and objective progression of disease was found in favour of the combination treatment. However, time from objective progression to death was longer in the group initially allocated to orchidectomy. Thus no difference was found in overall survival between the two treatment groups. The clinical significance of these differences requires further follow up and analysis.

Aged↗
PubMed1990

Zoladex and flutamide versus bilateral orchiectomy. A randomized phase III EORTC 30853 study. The EORTC GU Group.

A total of 327 patients with metastatic prostatic cancer were randomized to either bilateral orchiectomy or treatment with zoladex depot supplemented by flutamide 250 mg 3 qid. Statistically significant increases in time to subjective and objective progression were recorded in favor of the combination treatment. No differences in time to death by cancer or overall death were recorded. The clinical significance of these differences will be reassessed once additional follow-up is available and further analysis of the overall clinical material has been carried out.

Aged↗
PubMed1990

Quality of life and treatment of hormone resistant metastatic prostatic cancer. The EORTC Genito-Urinary Group.

72 patients with hormone resistant, progressing prostatic cancer completed a self-administered questionnaire to assess subjective morbidity and quality of life before they were entered into a phase III trial of estramustine (34) vs. mitomycin (38). At least one post-treatment assessment was available in 43 patients. This considerable degree of non-compliance is explained by practical problems related to completion and collection of the questionnaires in these rapidly deteriorating patients. Doctors underestimated subjective morbidity (pain, decreased performance status, nausea) in 30-50% of the cases. Decreased functional status, fatigue and pain were identified as the most frequent major morbidities before study entry. In most patients, treatment did not reduce this morbidity. The routine application of self-administered quality of life questionnaires has considerable practical problems but yields clinically worthwhile information about subjective morbidity. Simple but relevant monitoring of subjective morbidity by the patient should be mandatory in cancer trials where palliation is a major endpoint.

Attitude of Health Personnel↗
PubMed1989

Quality of life in patients with muscle-infiltrating bladder cancer and hormone-resistant prostatic cancer.

A questionnaire, filled in by the patient, was used to assess the quality of life of 65 patients with previously untreated T2-T4 NX MO bladder cancer and of 67 patients with hormone-resistant prostatic cancer. This study examines the initial questionnaire filled in before any nonsurgical treatment had been started in the patients referred to an oncological ward. The aim was to identify domains in which distress was frequent, in the hope of indicating where treatment directed forward improving the patients' quality of life should be directed. The questionnaires yielded reliable and valid data. Among bladder cancer patients micturition disturbances and sexual problems dominated. Bone pain, fatigue, sexual disturbances and interruption of social relationships were the most frequent and most severe complaints of prostatic cancer patients. It was concluded that routine quality of life evaluation by self-assessment questionnaires is possible in a clinical ward provided some assistance by the nursing staff is available. Future treatment in patients for whom palliation is the main goal of therapy should be concentrated on improving the quality of life in areas where distress is evident. The effect of treatment on quality of life could be monitored by similar questionnaires.

Activities of Daily Living↗