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Catherine M Tangen

Publications and source records attributed to Catherine M Tangen.

32 records · Page 2Linked to original sources
PubMed2004

Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter.

BACKGROUND: The optimal upper limit of the normal range for prostate-specific antigen (PSA) is unknown. We investigated the prevalence of prostate cancer among men in the Prostate Cancer Prevention Trial who had a PSA level of 4.0 ng per milliliter or less. METHODS: Of 18,882 men enrolled in the prevention trial, 9459 were randomly assigned to receive placebo and had an annual measurement of PSA and a digital rectal examination. Among these 9459 men, 2950 men never had a PSA level of more than 4.0 ng per milliliter or an abnormal digital rectal examination, had a final PSA determination, and underwent a prostate biopsy after being in the study for seven years. RESULTS: Among the 2950 men (age range, 62 to 91 years), prostate cancer was diagnosed in 449 (15.2 percent); 67 of these 449 cancers (14.9 percent) had a Gleason score of 7 or higher. The prevalence of prostate cancer was 6.6 percent among men with a PSA level of up to 0.5 ng per milliliter, 10.1 percent among those with values of 0.6 to 1.0 ng per milliliter, 17.0 percent among those with values of 1.1 to 2.0 ng per milliliter, 23.9 percent among those with values of 2.1 to 3.0 ng per milliliter, and 26.9 percent among those with values of 3.1 to 4.0 ng per milliliter. The prevalence of high-grade cancers increased from 12.5 percent of cancers associated with a PSA level of 0.5 ng per milliliter or less to 25.0 percent of cancers associated with a PSA level of 3.1 to 4.0 ng per milliliter. CONCLUSIONS: Biopsy-detected prostate cancer, including high-grade cancers, is not rare among men with PSA levels of 4.0 ng per milliliter or less--levels generally thought to be in the normal range.

Aged↗
PubMed2004

Implementation of the Prostate Cancer Prevention Trial (PCPT).

The Prostate Cancer Prevention Trial is a randomized double blind chemoprevention trial of 18,882 men. It is designed to test the difference in the histologically proven prostate cancer prevalence between a group of participants given finasteride and another given placebo for 7 years. We present an overview of the study design, details of the administrative structure of the study and a description of the successful implementation of the accrual phase.

Chemoprevention↗
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

Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer.

BACKGROUND: Despite aggressive local therapy, patients with locally advanced bladder cancer are at significant risk for metastases. We evaluated the ability of neoadjuvant chemotherapy to improve the outcome in patients with locally advanced bladder cancer who were treated with radical cystectomy. METHODS: Patients were enrolled if they had muscle-invasive bladder cancer (stage T2 to T4a) and were to be treated with radical cystectomy. They were stratified according to age (less than 65 years vs. 65 years or older) and stage (superficial muscle invasion vs. more extensive disease) and were randomly assigned to radical cystectomy alone or three cycles of methotrexate, vinblastine, doxorubicin, and cisplatin followed by radical cystectomy. RESULTS: We enrolled 317 patients over an 11-year period, 10 of whom were found to be ineligible; thus, 154 were assigned to receive surgery alone and 153 to receive combination therapy. According to an intention-to-treat analysis, the median survival among patients assigned to surgery alone was 46 months, as compared with 77 months among patients assigned to combination therapy (P=0.06 by a two-sided stratified log-rank test). In both groups, improved survival was associated with the absence of residual cancer in the cystectomy specimen. Significantly more patients in the combination-therapy group had no residual disease than patients in the cystectomy group (38 percent vs. 15 percent, P<0.001). CONCLUSIONS: As compared with radical cystectomy alone, the use of neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin followed by radical cystectomy increases the likelihood of eliminating residual cancer in the cystectomy specimen and is associated with improved survival among patients with locally advanced bladder cancer.

Adult↗
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

Metastatic carcinoma of the prostate: identifying prognostic groups using recursive partitioning.

PURPOSE While in patients with metastatic prostate cancer median survival is approximately 30 months when treated with hormonal therapy, there is substantial interpatient variation. To explain better the outcome in patients with advanced disease we developed a set of prognostic groups within a large-scale clinical trial. MATERIALS AND METHODS Southwest Oncology Group Study 8894 was a randomized prospective clinical trial that compared orchiectomy and flutamide to orchiectomy and placebo. Using the technique of recursive partitioning we analyzed 5-year survival outcomes using a substantial number of patient, treatment and disease related variables to develop a set of prognostic groups with significant differences in survival. RESULTS Of 1,286 eligible patients 1,076 had sufficient data for analysis. The patient data set was split to allow prognostic group development in the first half of patients, followed by validation in the second half of patients accrued to the study. After pruning the regression tree 4 factors had a major impact on outcome, namely appendicular versus axial disease, performance status 0 versus 1 to 3, prostate specific antigen less than 65 versus 65 ng./ml. or greater and Gleason score less than 8 versus 8 or greater. Using these criteria 3 prognostic groups were developed, including a good (hazards ratio 1), intermediate (hazards ratio 1.8) and poor (hazards ratio 2.8) group. Five-year survival estimates in the 3 groups were 42%, 21% and 9%, respectively. Using the validation test set similar 5-year survival estimates for the 3 groups of 46%, 25% and 14%, respectively.CONCLUSIONS These data from a large-scale randomized clinical trial provide a validated set of easily applied prognostic groups. We hope that our results may be validated by other investigators and we would encourage the future reporting of outcomes in patients with advanced prostate cancer using these prognostic groupings. Risk stratification is helpful for designing clinical trials and individual treatment, and it should be incorporated into future reports of outcomes of patients with metastatic disease.

Adenocarcinoma↗
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

The possible role of postoperative azotemia in enhanced survival of patients with metastatic renal cancer after cytoreductive nephrectomy.

Cytoreductive nephrectomy prior to systemic therapy significantly increases survival in patients with metastatic renal cancer. This result is generally ascribed to the benefits of resection of the primary tumor including reduction of tumor burden, removal of a source for growth factors and metastases, and enhanced immune response. On the basis of mathematical models of tumor invasion, we propose that the observed effects of cytoreductive nephrectomy may be caused by resection of the kidney rather than the cancer. The models predict that the graded metabolic acidosis associated with mild renal failure after unilateral nephrectomy may alter the dynamics of the tumor-host interface sufficiently to reduce and even reverse the rate of invasion. A review of patient data from the surgical arm of the Southwest Oncology Group (SWOG) 8949(2) trial demonstrates significantly improved survival in patients who experienced postoperative increase in blood urea nitrogen (BUN) and creatinine compared with those who did not (17-month survival versus 4-month survival; P = 0.0007). This is generally consistent with the predictions of the mathematical models. If confirmed, these results suggest novel and broadly applicable tumor therapies.

Acidosis↗
PubMed2002

SWOG-9510: evaluation of topotecan in hormone refractory prostate cancer: a Southwest Oncology Group study.

BACKGROUND: Prostate cancer is the most common malignancy in American men, and as many as 70% of those initially treated for localized disease will ultimately progress and be considered candidates to receive therapy for metastatic cancer [Fuks et al.: Int J Radiat Oncol Bio Phys 21:537-547, 1991; Chodak et al.: N Engl J Med 330:246-248, 1994]. Although most will respond initially to hormone manipulation, essentially all will fail and require additional therapy. No standard chemotherapy approach has been shown to prolong survival significantly, and new agents are desperately needed. Topotecan is a new topoisomerase-1 inhibitor whose early investigation suggested possible activity in hormone-refractory prostate cancer. METHODS: In this phase II trial, patients having failed one or two prior androgen ablative therapies were treated with 21-day continuous intravenous infusions of topotecan at a dose of 0.5 mg/m(2) per day every 28 days. RESULTS: Twenty-six eligible patients were entered on the study. There were no confirmed tumor responses. Median survival was 9 months. The most common toxicities were hematologic, with 8 of 24 assessable patients experiencing grade 4 toxicity. CONCLUSION: Topotecan infusions at this dose are ineffective in the management of hormone-refractory prostate cancer.

Aged↗
PubMed2002

Inflammation and coagulation factors in persons > 65 years of age with symptoms of depression but without evidence of myocardial ischemia.

Depression is associated with increased cardiovascular disease, but the underlying mechanisms are not well understood. This study examines associations of depressive symptoms with inflammation and coagulation factors in persons aged > 65 years. Blood samples were obtained from 4,268 subjects free of cardiovascular disease (age 72.4 +/- 5.5 years, 2,623 women). Inflammation markers were C-reactive protein (CRP), white blood cell (WBC) count, total platelet count, and albumin; coagulation factors included factors VIIc and VIIIc and fibrinogen. Depression was assessed with the Center for Epidemiologic Studies Depression scale, and states of energy depletion with a validated exhaustion index. Statistical adjustments were made for risk factors (age, sex, race, systolic blood pressure, smoking status, diabetes mellitus) and physical measures of frailty (isometric handgrip, timed 15-feet walk test, activity level). Depression was associated with elevated CRP (3.31 +/- 0.10 vs 3.51 +/- 0.21 mg/L), WBC (6.14 +/- 0.03 vs 6.43 +/- 0.11 10(6)/L), fibrinogen (319 +/- 1 vs 326 +/- 3 mg/dl), and factor VIIc (124.6 +/- 0.6% vs 127.2 +/- 1.3%; all p <0.05). Exhaustion also was related to elevated inflammation and coagulation markers (p < 0.05). Exhausted men had markedly elevated CRP levels (6.82 +/- 2.10 mg/L) versus nonexhausted men (3.05 +/- 0.16: p = 0.007). After adjustment for control variables, exhaustion remained associated with albumin (p = 0.033), fibrinogen (p = 0.017), CRP (p = 0.066), and WBC (p = 0.060), whereas associations of depressive symptoms with biochemistry measures lost statistical significance. Thus, depression and exhaustion are associated with low-grade inflammation and elevated coagulation factors in persons aged > 65 years.

Aged↗
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↗
PubMedDate not supplied

A phase II clinical trial of oral bropirimine in combination with intravesical bacillus Calmette-Guérin for carcinoma in situ of the bladder: a Southwest Oncology Group Study.

OBJECTIVES: To estimate the probability of response when intravesical bacille Calmette-Guérin (BCG) is given in combination with oral bropirimine for bladder carcinoma in situ, and to evaluate toxicity when the 2 agents are combined. METHODS: A total of 51 patients with histologic evidence of carcinoma in situ and no prior treatment with BCG or bropirimine were enrolled in a cooperative group multicenter phase II trial. Initial treatment included Tice BCG 50 mg weekly for 6 weeks and oral bropirimine 3.0 g/day for 3 consecutive days each week for 12 weeks. Response was assessed after 12 weeks by cystoscopy, biopsy, and barbotage cytology. Most patients received a second course followed by an identical assessment. Toxicity was recorded according to the Southwest Oncology Group toxicity criteria. RESULTS: A total of 51 patients were enrolled and treated. There were 42 patients who were eligible and valuable for response and toxicity. There were 28 complete responders (67%, 50% to 80% 95% confidence interval). The 5-year progression-free survival estimate is 53%, and the 5-year survival estimate is 80%. There were no deaths, 2 patients had grade 4 toxicity, 14 grade 3 toxicity, 17 grade 2 toxicity, 6 grade 1 toxicity, and only 3 had no toxicity reported as their worst toxicity grade. CONCLUSIONS: The combination failed to show an estimated response higher than 80%. It is not recommended that further evaluation of this combination be conducted.

Aged↗