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Ian M Thompson

Publications and source records attributed to Ian M Thompson.

At least 73 records · Page 4Linked to original sources
PubMed2004

The Prostate Cancer Prevention Trial: current status.

PURPOSE: The rationale, design considerations and current status of the Prostate Cancer Prevention Trial (PCPT) are presented. MATERIALS AND METHODS: The design considerations for a prevention study involving finasteride were reviewed. Most notable was the end of study biopsy planned for all participants to eliminate any detection bias caused by the effect of finasteride on prostate specific antigen. RESULTS: During a 3-year period 18,882 men were randomized in the PCPT. The final end of study biopsy is planned for May 2004. The study was closed 15 months before the final anticipated participant biopsy by the independent Data and Safety Monitoring Committee due to a 24.8% reduction in prostate cancer with finasteride. CONCLUSIONS: The extraordinary accrual of PCPT of healthy men in a prospective study to test an intervention for prostate cancer prevention illustrates the potential for future studies. The positive results of the trial as well as many observations that have been made of the study population argue for increased emphasis on prevention research for highly prevalent genitourinary malignancies.

Anticarcinogenic Agents↗
PubMed2004

Prostate cancer chemoprevention: an overview of United States trials.

PURPOSE: We review the current status of clinical trials investigating the use of interventions designed to reduce the risk of prostate cancer. MATERIALS AND METHODS: A comprehensive review of the literature was conducted, which included the Ovid database and recent abstract proceedings from national meetings relevant to chemoprevention trials in prostate cancer. All clinical trials sponsored by the National Institutes of Health and National Cancer Institute in the United States were included. RESULTS: A total of 11 randomized controlled trials were found to be currently recruiting patients in the United States. These randomized controlled trials are designed to investigate the efficacy of a variety of agents ranging from dietary supplements to laboratory manufactured drugs, such as finasteride and cyclooxygenase-2 inhibitors, for the primary chemoprevention of prostate cancer. CONCLUSIONS: Chemoprevention of prostate cancer is currently being tested in a wide range of clinical trials. These studies have the potential to fundamentally alter the current approach to prostate cancer management.

Animals↗
PubMed2004

Statistical design issues and other practical considerations for conducting phase III prostate cancer prevention trials.

PURPOSE: We briefly describe the purpose of phase II studies as a source of preliminary data for phase III prevention trials, and address statistical and other practical considerations for phase III prostate cancer prevention trials. MATERIALS AND METHODS: Objectives of 2 types of phase II studies and general criteria for validating surrogate end points are described, and statistical considerations needed for planning a phase III prevention trial are explained, including selection of an appropriate study population and end point, the corresponding expected event rate, estimates of loss to followup, and death and compliance rates. If a preventive agent has an impact on the ability to detect prostate cancer, additional study design considerations are then made. Other practical issues are addressed, including collection of biological materials for correlative studies, assessment of quality of life measures and the addition of ancillary studies that may include the collection of additional end points unrelated to prostate cancer. RESULTS: The Southwest Oncology Group is coordinating 2 recently reported phase III prostate cancer prevention trials. The Prostate Cancer Prevention Trial final results of 18,882 men randomized to either finasteride or placebo, and the Selenium and Vitamin E Cancer Prevention Trial has accrued more than half of its goal of 32,400 men. These studies are used to illustrate some statistical design features. CONCLUSIONS: The aforementioned trials provide valuable lessons in the successful design and conduct of phase III prostate cancer prevention trials.

Anticarcinogenic Agents↗
PubMed2004

Prognostic value of anemia in newly diagnosed metastatic prostate cancer: a multivariate analysis of southwest oncology group study 8894.

PURPOSE: Previously reported association of anemia with shorter survival in newly diagnosed metastatic prostate cancer may simply reflect extent of disease. The impact of anemia on response to androgen deprivation is not known. We examined the prognostic value of anemia in a multivariate analysis that included disease extent and other tumor and demographic covariates in 957 patients starting hormonal therapy for metastatic prostate cancer as part of Southwest Oncology Group study 8894. MATERIALS AND METHODS: The multivariate associations of disease and patient measures with anemia (hemoglobin less than 12 gm/dl) were evaluated with a logistic regression model. The associations between hemoglobin and survival and progression-free survival (PFS) were evaluated using a proportional hazards model, and included indicators for quartiles of hemoglobin and baseline covariates. Prostate specific antigen (PSA) normalization (PSAN, or PSA of 4 ng/ml or less) was evaluated with a logistic model. RESULTS: Quartiles of hemoglobin were 10.1 or less, 10.2 to 12.0, 12.1 to 13.4 and greater than 13.4 gm/dl. In a multivariate model anemia was significantly associated (p <0.02) with being black, performance status 2 to 3 (vs 0 to 1), extensive disease and higher PSA. Anemia was inversely associated with prior therapy with curative intent and with Gleason score 6 to 7 (vs 5 or less), and was not associated with age or bone pain. After adjusting for potential confounders, lower hemoglobin was associated with shorter survival and PFS, and lower likelihood of PSAN with hormonal therapy (p <0.01). CONCLUSIONS: In this newly diagnosed metastatic prostate cancer sample, anemia was common and was associated with shorter survival, shorter PFS, and lower likelihood of PSAN with hormonal therapy after adjustment for disease status and other covariates.

Aged↗
PubMed2003

Estimating the impact of new clinical trial proven cancer therapy and cancer chemoprevention on population mortality: the Karnofsky Memorial lecture.

PURPOSE: The 31-year "war on cancer" has focused largely on therapeutic (as opposed to preventative) cancer research, which, in both the public and private sector, has received the majority of funding. Meanwhile the prevention of cancer has received less attention. PATIENTS AND METHODS: We analyzed eight positive phase III therapeutic trials of the Southwest Oncology Group, and estimated how the observed improvements in survival from the new therapies would impact mortality at the population level (utilizing Surveillance, Epidemiology, and End Results-data). We compared these results with the impact of the Prostate Cancer Prevention Trial. The measure of impact was person-years saved in the first 5 years. RESULTS: Estimates of person-years saved in the first 5 years included 28,534 from improved treatment of localized bladder cancer and 26,241 from improved treatment of advanced lung cancer, representing, respectively, 31.4% and 2.8% of the person-years which could have been saved for these diseases (the "relative impact of new treatment on survival"). The new therapies from all eight positive phase III trials would have saved 114,641 person-years over the first 5 years. The estimate from the Prostate Cancer Prevention Trial was 99,441 person-years over the first 5 years. CONCLUSION: New cancer therapies have a proven and quantifiable impact on population mortality. Successful cancer prevention has a similarly large impact. However, federal funding for cancer prevention is less than half that of cancer treatment. As a result of its enormous potential for extending life, cancer prevention warrants increased funding and support from federal funding agencies.

Antineoplastic Agents↗
PubMed2003

The influence of finasteride on the development of prostate cancer.

BACKGROUND: Androgens are involved in the development of prostate cancer. Finasteride, an inhibitor of 5alpha-reductase, inhibits the conversion of testosterone to dihydrotestosterone, the primary androgen in the prostate, and may reduce the risk of prostate cancer. METHODS: In the Prostate Cancer Prevention Trial, we randomly assigned 18,882 men 55 years of age or older with a normal digital rectal examination and a prostate-specific antigen (PSA) level of 3.0 ng per milliliter or lower to treatment with finasteride (5 mg per day) or placebo for seven years. Prostate biopsy was recommended if the annual PSA level, adjusted for the effect of finasteride, exceeded 4.0 ng per milliliter or if the digital rectal examination was abnormal. It was anticipated that 60 percent of participants would have prostate cancer diagnosed during the study or would undergo biopsy at the end of the study. The primary end point was the prevalence of prostate cancer during the seven years of the study. RESULTS: Prostate cancer was detected in 803 of the 4368 men in the finasteride group who had data for the final analysis (18.4 percent) and 1147 of the 4692 men in the placebo group who had such data (24.4 percent), for a 24.8 percent reduction in prevalence over the seven-year period (95 percent confidence interval, 18.6 to 30.6 percent; P<0.001). Tumors of Gleason grade 7, 8, 9, or 10 were more common in the finasteride group (280 of 757 tumors [37.0 percent], or 6.4 percent of the 4368 men included in the final analysis) than in the placebo group (237 of 1068 tumors [22.2 percent], P<0.001 for the comparison between groups; or 5.1 percent of the 4692 men included in the final analysis, P=0.005 for the comparison between groups). Sexual side effects were more common in finasteride-treated men, whereas urinary symptoms were more common in men receiving placebo. CONCLUSIONS: Finasteride prevents or delays the appearance of prostate cancer, but this possible benefit and a reduced risk of urinary problems must be weighed against sexual side effects and the increased risk of high-grade prostate cancer.

5-alpha Reductase Inhibitors↗
PubMed2003

The selenium and vitamin E cancer prevention trial.

BACKGROUND: Evidence suggests that both selenium and vitamin E reduce the risk of prostate cancer. The Selenium and Vitamin E Cancer Prevention Trial (SELECT) is a randomized, prospective, double-blind study designed to determine whether selenium and vitamin E alone and in combination can reduce the risk of prostate cancer among healthy men. MATERIALS AND METHODS: The preclinical and epidemiological evidence supporting a role for selenium and vitamin E as chemopreventive agents in prostate cancer are reviewed, and details of the trial design are presented. RESULTS. Preclinical, epidemiological, and phase III data from randomized, placebo-controlled clinical trials suggest that both selenium and vitamin E have potential efficacy in prostate cancer prevention. SELECT is a 2x2 factorial study with an accrual goal of 32,400 men with nonsuspicious DRE and serum PSA of 4 ng/ml or lower. CONCLUSIONS: SELECT is the second large-scale study of chemoprevention for prostate cancer. Enrollment began in 2001 with final results anticipated in 2013.

Clinical Trials as Topic↗
PubMed2003

The Prostate Cancer Prevention Trial: design, status, and promise.

The Prostate Cancer Prevention Trial is the first phase III (randomized, placebo-controlled, prospective) population-based study to determine whether the risk of prostate cancer can be reduced. Between 1994 and 1997, 18,882 men were randomized to either finasteride or placebo at 219 sites in the United States. The study design included annual digital rectal examination and PSA determinations with PSA performed centrally with reports provided to sites corrected for treatment arm (as finasteride lowers PSA level). Because of a number of potential biases that could confound disease ascertainment all patients were scheduled for an end-of-study prostate biopsy. End-of-study prostate biopsies began in 2000, and the final biopsy is expected in 2004, with results of the study anticipated shortly thereafter. The high participant interest and extensive data collected for this study demonstrate the extraordinary opportunity for chemoprevention trials of prostate cancer in the United States

Clinical Trials as Topic↗
PubMed2003

Prevention of prostate cancer with finasteride: US/European perspective.

PURPOSE: Prostate cancer is the most common male cancer, affecting one man in six. Prevention of this disease, even in a subset of patients would have a significant impact on public health. The results of the National Cancer Institute-sponsored Prostate Cancer Prevention Trial demonstrate that finasteride causes a substantial risk reduction across all known risk groups. We herein amplify on the results of this trial to assist patients and physicians in reaching individualized decisions. MATERIALS AND METHODS: The results of the Prostate Cancer Prevention Trial were reviewed. RESULTS: The PCPT demonstrated a 24.8% reduction in prostate cancer risk with the administration of finasteride. High-grade cancers were noted in 6.4% of finasteride patients compared to 5.1% of men receiving placebo. The increase in high-grade tumors was seen within one year of finasteride exposure and did not increase over time. This observation, combined with previous evidence demonstrating an alteration in cytologic and architectural features of prostate cancer with hormonal therapy suggests that the differences in high-grade disease may be an artifact and that application of Gleason grading to these tumors may not be appropriate. DISCUSSION: Men should be presented the benefits and risks of taking finasteride and be assisted in integrating their sexual and urinary symptoms into their decision-making process. Blanket statements for or against the use of this medication ignore patient preferences and differential risk-benefit profiles from finasteride.

Aged↗
PubMed2003

Spontaneous regression of choroidal metastasis from renal cell carcinoma.

PURPOSE: To describe a patient with choroidal metastasis from renal cell carcinoma that spontaneously regressed after nephrectomy. DESIGN: Interventional case report. METHOD: A 48-year-old Hispanic woman presented with reduced vision in the left eye attributable to an elevated choroidal lesion and associated exudative retinal detachment. Oncology workup revealed a left kidney renal cell carcinoma with pulmonary metastases. The patient underwent primary nephrectomy, without specific treatment of choroidal or pulmonary metastases. RESULTS: The metastatic choroidal lesion regressed and the retinal detachment completely resolved, as evidenced by fundus photographs and ultrasonography. CONCLUSIONS: Choroidal metastasis from renal cell carcinoma may spontaneously regress after removal of the primary tumor.

Carcinoma, Renal Cell↗
PubMed2003

Chemoprevention of prostate cancer. Focus on key opportunities and clinical trials.

By 2004-2005, the final results of the Prostate Cancer Prevention Trial should be available. Within several years thereafter, results of the SELECT should be available. The growing list of potential agents for prostate cancer prevention continues to grow and includes COX-2 inhibitors, vitamin D, dietary interventions (soy, isoflavenoids, low-fat diet), and many others. As prospective trials are completed and molecular genetic correlations are developed, it is almost certain that specific recommendations, tailored to the individual patient, will be developed. Ultimately, through these efforts, it can be anticipated that the primary focus for control of prostate cancer will shift from early detection and treatment to prevention.

Antioxidants↗
PubMed2003

Prostate cancer prevention: what do we know now and when will we know more?

Prostate cancer prevention is now one of the most aggressively investigated areas of urologic oncology, with > 30,000 men currently participating in clinical trials in the United States alone. The Prostate Cancer Prevention Trial will complete end-of-study prostate biopsies in May 2004, and the Selenium and Vitamin E Cancer Prevention Trial is rapidly reaching its accrual goal 1-2 years ahead of schedule. These 2 studies will give definitive answers regarding 3 of the most important potential preventive interventions: finasteride, vitamin E, and selenium. Many phase II and biomarker-modulation studies are also ongoing, testing a host of other interventions. It is hoped that, within a short period of time, the clinician will be provided with strategies to reduce the risk of the disease.

Antioxidants↗
PubMed2003

Ten-year survival in patients with metastatic prostate cancer.

The objective of this analysis is to identify baseline covariates that predict which patients will be long-term survivors with metastatic prostate cancer. We analyzed data from Southwest Oncology Group (SWOG) S8894, a clinical trial in men with newly diagnosed metastatic prostate cancer, to evaluate pretreatment characteristics associated with 10-year survival. There were 1286 eligible patients randomized to this study. Of these, 794 have been followed for > or = 10.5 years and are included in the analyses. Proportional odds models were used to predict 3 survival categories (survival for < 5 years, 5 up to 10 years, and > or = 10 years). Baseline patient and disease characteristics investigated were protocol treatment (flutamide vs. placebo), severity of disease, SWOG performance status (PS), bone pain, Gleason score, race, age, and prostate-specific antigen (PSA) level at study entry. Of the 794 evaluable patients, 77% lived < 5 years, 16% lived 5 up to 10 years, and 7% lived > or = 10 years. Factors predicting a statistical significant association with longer survival (P < 0.05) included minimal disease, better PS, no bone pain, lower Gleason score, and lower PSA level. All but PS were also significant in multivariate analyses. However, only 13% of patients (5 of 38) who lived > or = 10 years were correctly predicted in their survival category based on the model, whereas 98% (405 of 414) who died within the first 5 years were correctly predicted. Although statistically significant baseline characteristics were identified in this clinical trial, they did not accurately predict the survival interval to which a patient belonged.

Adenocarcinoma↗
PubMed2002

Neoadjuvant therapy before radical prostatectomy for clinical T3/T4 carcinoma of the prostate: 5-year followup, Phase II Southwest Oncology Group Study 9109.

PURPOSE: Several investigators have examined the role of hormonal therapy before definitive local therapy for locally advanced prostate cancer to improve outcome. We evaluated the resectability rate and clinical response rate to 16 weeks of total androgen blockage therapy for clinically locally prostate cancer before radical prostatectomy, and progression-free survival in this multi-institutional study. MATERIALS AND METHODS: Southwest Oncology Group 9109 was a phase II feasibility study designed to treat patients with clinical stage C prostate cancer (T3, T4, N0 and M0). Cases were classified by stage T3 versus T4 and bulky (greater than 4 cm.) versus nonbulky (or less 4 cm.) disease. The neoadjuvant agents used were goserelin and flutamide before radical prostatectomy. RESULTS: A total of 62 patients were accrued to the study and 1 patient was ineligible. There were 2 protocol deviations and these patients refused to undergo prostatectomy after hormonal therapy. Four patients went off protocol treatment because they were not considered surgical candidates. The racial distribution was 72% white, 20% black, 7% Hispanic and 2% Asian. Clinical stage at diagnosis was T3 in 97% and T4 in 3% of cases. Of the patients 39% were diagnosed with bulky disease. Of the 61 eligible patients 55 (90%) underwent a prostatectomy. The 5-year progression-free survival estimate was 70% (24 of 61 cases failed) and the 5-year survival estimate was 90% (11 of 61 deaths). Most of the patients in this trial would have been considered inoperable and referred to radiation oncology. CONCLUSIONS: Neoadjuvant hormonal therapy followed by radical prostatectomy is reasonable and appropriate for clinical stage T3 prostate cancer. A progression-free and overall 5-year survival of 70% and 90%, respectively, compares favorably to Radiation Therapy Oncology Group neoadjuvant trial outcomes for this stage of prostate cancer.

Aged↗
PubMed2002

Androgen receptor length polymorphism associated with prostate cancer risk in Hispanic men.

PURPOSE: The transcriptional activation domain of the androgen receptor gene includes a CAG repeat length polymorphism. A smaller number of repeats is reported to increase the risk of prostate cancer. We investigated the association of CAG repeat length and the risk of prostate cancer in a case-control study of Hispanic men. MATERIALS AND METHODS: To estimate the magnitude of the association of repeat length with prostate cancer risk, samples from 82 white patients of Hispanic origin (Hispanic) with prostate cancer and 145 Hispanic controls were genotyped. To determine the allelic distribution of repeats by race/ethnicity we genotyped 132 black men, 163 white men of nonHispanic origin (white) and 175 Hispanic men with no family history of prostate cancer, and performed pairwise comparison. RESULTS: In the case-control study of Hispanic men with a repeat length of 18 or less versus greater than 18 we found an approximately 3-fold increased risk of prostate cancer (OR 2.7, 95% CI 1.21 to 6.01, t test p = 0.013, age adjusted OR 3.03, 95% CI 1.27 to 7.26). The distribution of alleles differed significantly by race/ethnicity. The mean prevalence of short CAG repeat alleles plus or minus SD was higher in black than in white men (19.8 +/- 3.2 versus 21.8 +/- 2.7, t test p <0.0001) and lower in Hispanic men than in other white men (22.7 +/- 3.3, t test p = 0.014). CONCLUSIONS: To our knowledge, our study represents the first case-control study of the androgen receptor gene in a Hispanic population and provides evidence of the increased prostate cancer risk associated with short CAG repeats. Our results suggest that short CAG repeats are associated with an increased prostate cancer risk in Hispanic men.

Adult↗