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Biomedical subjects

C Tangen

Publications and source records attributed to C Tangen.

12 recordsLinked to original sources

Association of African-American ethnic background with survival in men with metastatic prostate cancer.

BACKGROUND: African-American men have earlier onset of prostate cancer, higher prostate-specific antigen (PSA) levels, more advanced stage at diagnosis, and higher mortality than white men. It is not known whether the poorer survival of African-American men with prostate cancer reflects their later stage at diagnosis or differences in the basic biology of their disease. To evaluate this question, we examined outcomes of African-American and white men with metastatic prostate cancer in the context of a randomized clinical trial. METHODS: Southwest Oncology Group Study 8894 was a randomized phase III trial that compared orchiectomy with or without flutamide in men with metastatic prostate cancer. Using data from 288 African-American and 975 white men in the trial, we conducted a proportional hazards regression analysis to determine if ethnicity was an independent predictor of survival. All statistical tests were two-sided. RESULTS: African-American men were more likely than white men to have extensive disease and bone pain and had poorer performance status, younger age at study entry, higher Gleason score, and higher PSA levels. After adjustment for these prognostic variables, the hazard ratio (HR) for all-cause mortality for African-American men relative to white men was 1.23 (P: =.018). Further adjustment for initial quality-of-life assessments also resulted in higher HRs associated with African-American ethnicity relative to white ethnicity (HR = 1.39; P: =.007). CONCLUSIONS: African-American men with metastatic prostate cancer have a statistically significantly worse prognosis than white men that cannot be explained by the prognostic variables explored in this study. These data should give increased impetus for efforts to detect the disease early in African-American men and for the development of more effective therapies based on potential biologic differences in this ethnic group.

Black or African American↗

Estrogen use, APOE, and cognitive decline: evidence of gene-environment interaction.

OBJECTIVE: APOE-epsilon4 increases the risk of cognitive decline, while elderly women who take estrogen may have less risk of cognitive decline. The authors sought to determine whether estrogen use modifies the association between APOE-epsilon4 and cognitive decline. METHOD: - As part of the Cardiovascular Health Study, 3,393 Medicare-eligible women (> or =65 years) were randomly selected and recruited from Sacramento County, CA; Washington County, MD; Forsyth County, NC; and Pittsburgh, PA. Cognitive testing was administered annually; the authors studied the 2,716 women with cognitive testing on > or =2 visits. They analyzed change in score on the Modified Mini-Mental State Examination (3MS) as a function of estrogen use, APOE genotype, and baseline common and internal carotid artery wall thickening. RESULTS: A total of 297 (11%) women were current estrogen users and 336 (12%) were past estrogen users. Over the 6-year average follow-up, baseline current users declined 1.5 points on the 3MS whereas never users declined 2.7 points (p = 0.023). Compared with epsilon4-negative women, epsilon4-positive women had a greater adjusted hazard ratio of cognitive impairment (3MS < 80), hazard risk [HR] = 1.47; 95% CI, 1.13 to 1.90. There was an interaction between estrogen use and epsilon4 presence (p = 0.037). Among epsilon4-negative women, current estrogen use reduced the risk of adjusted cognitive impairment compared with never users by almost half (HR = 0.59; 95% CI, 0.36 to 0.99), whereas, it did not reduce the risk among epsilon4-positive women (current use, HR = 1.33; 95% CI, 0.74 to 2.42). Compared with never use, current estrogen use was associated with less internal and common carotid wall thickening in epsilon4-negative women but not in epsilon4-positive women (p for interaction < 0.05 for both). Differences remained after adjusting for age, education, race, and stroke. CONCLUSIONS: Estrogen use was associated with less cognitive decline among epsilon4-negative women but not epsilon4-positive women. Potential mechanisms, including carotid atherosclerosis, by which epsilon4 may interact with estrogen and cognition warrant further investigation.

Aged↗

Severe disruptive vocalizers.

OBJECTIVES: To describe the most severe disruptive vocalizers in nursing facilities, in regard to their clinical and behavioral characteristics, staff responses, and treatments used, and to report on their prognosis over 6 months. DESIGN: A longitudinal cohort study. SETTING: One hundred seven skilled nursing facilities. PARTICIPANTS: The 203 residents who were among the two most disruptive vocalizers in their respective facilities and who vocalized at least 2 hours a day. MEASUREMENTS: Telephone interviews of licensed nursing staff who cared for the subjects, conducted at baseline, 2, 4, and 6 months. Data gathered included subject demographics, physical function, diagnoses, medication and restraint use, behavioral problems, vocalization characteristics, treatments used, and status at follow-up. RESULTS: Subjects tended to have dementia, to be dependent in most activities of daily living, to have multiple medical problems, to be physically restrained (48%), and to be taking psychotropic medication (76%). Nearly all (95%) were audible at least 50 feet away, with loudness associated with more severe cognitive impairment (OR 4.90, P = .001). When subjects who primarily made nonverbal noises ("screamers") were compared with those whose predominant expressions were words ("talkers"), hearing impairment, severe cognitive impairment, and greater dependency in activities of daily living characterized the screamers. Staff reported trying a variety of treatments with all subjects, often with little success. Two months after enrollment, 66% of surviving subjects vocalized fewer hours than at baseline, and 45% were rated as improved. Independent predictors of improvement included greater ADL independence, hearing and vision problems, shorter length of stay, urinary incontinence, and use of a treatment other than one-on-one interventions. Nearly one-quarter of subjects (23.4%) died within 6 months. Baseline factors associated independently with a higher probability of death included age, use of activity intervention, physical abusiveness, and absence of wandering. CONCLUSION: Severe disruptive vocalization is associated with severe cognitive and physical impairment and with a high probability of mortality within 6 months. Subcategorization of severe vocalizers by vocalization type or other associated factors may be useful for prognostic and treatment purposes.

Activities of Daily Living↗

Docetaxel (Taxotere) and estramustine versus mitoxantrone and prednisone for hormone-refractory prostate cancer: scientific basis and design of Southwest Oncology Group Study 9916.

Hormone-refractory prostate cancer is the terminal step in the natural history of prostate cancer. To date, no chemotherapeutic agents have been shown to impact clinical outcome at this stage. Recently, the Food and Drug Administration approved the combination of mitoxantrone and prednisone based solely on its superior palliative effects as compared to steroids alone in 2 randomized trials. Progress in biologically driven drug development has led to the identification of several estramustine-based regimens that, although based on single institution experience, appear to have at least a comparable but very promising level of activity in hormone-refractory prostate cancer patients. One such combination, estramustine plus docetaxel (Taxotere; Rhône-Poulenc Rorer, Collegeville, PA), is particularly attractive because of its convenient schedule and side effect profile. To objectively assess the therapeutic benefit of this combination, the Southwest Oncology Group is initiating a randomized phase III trial comparing estramustine and docetaxel with the standard arm of mitoxantrone and prednisone using time to progression and survival as the primary end points. Secondary end points will include toxicity profiles, assessments of quality of life parameters, and magnitude of decline of prostate-specific antigen levels between the two treatment arms.

Adenocarcinoma↗

Phase II study of 5-fluorouracil and folinic acid in the treatment of patients with advanced gastric cancer. A Southwest Oncology Group study.

BACKGROUND: The biochemical modulation of 5-fluorouracil (5-FU) by the reduced folate folinic acid (FA) in the treatment of patients with advanced gastric cancer was examined. METHODS: The Southwest Oncology Group performed parallel randomized Phase II trials of two schedules of 5-FU and FA in 80 patients with advanced gastric cancer. Of 76 analyzable patients, 36 were randomized to receive bolus FA (200 mg/m2, days 1-4) along with continuous infusion 5-FU (1000 mg/m2, days 1-4) and 40 were randomized to receive bolus FA (200 mg/m2, days 1-5) before the bolus 5-FU (375 mg/m2, days 1-5). RESULTS: There were three (8%) partial responses (95% confidence interval [CI] 2%-22%) on the continuous infusion arm. The bolus arm had two (5%) complete responses and six (15%) partial responses for an overall response rate of 20% (95% CI 9%-36%). The median duration of response was 4.6 months for the infusion patients and 16.6 months for the bolus patients. Survival was poor, with median survival of 5 months on both regimens. Gastrointestinal toxicity was substantial, with Grade 3 mucositis observed in 36% of patients on the continuous infusion regimen versus only 10% of patients on the bolus regimen. Grade 3 or higher hematologic toxicity occurred more often in the bolus arm than in the continuous infusion arm (28% vs. 14%, respectively). Two toxic deaths occurred, one related to sepsis the other secondary to coronary insufficiency. CONCLUSIONS: Biochemical modulation of 5-FU by FA using the dose and schedules tested has only modest activity in the treatment of advanced gastric cancer.

Adenocarcinoma↗

Phase II trial of piroxantrone in gastric carcinoma. A Southwest Oncology Group study.

Twenty-one evaluable patients with advanced gastric adenocarcinoma were treated with piroxantrone at a dose of 150 mg/m2 intravenously every 21 days. One objective response was seen for an overall response rate of 5% (95% confidence interval 0-24%). Toxicities of grade > or = 3 were primarily hematologic and seen in 13/21 patients. Piroxantrone has minimal activity against gastric adenocarcinoma and no further investigation of this agent on this schedule in this disease is recommended.

Adenocarcinoma↗

An evaluation of the carcinoembryonic antigen (CEA) test for monitoring patients with resected colon cancer.

OBJECTIVE: To determine the effectiveness of carcinoembryonic antigen (CEA) monitoring in detecting surgically curable recurrence of colon cancer. DESIGN: Clinical data were collected from a national surgical adjuvant trial in which CEA monitoring was elective. SETTING: Cancer centers, universities, and community clinics. PATIENTS: A total of 1216 patients with resected colon cancer, 1017 (84%) of whom had CEA monitoring. MAIN OUTCOME MEASURES: Sensitivity and specificity of CEA testing for cancer recurrence and CEA-motivated diagnostic and surgical interventions and their end results. RESULTS: Among 417 monitored patients with recurrence, 59% had a preceding elevation of CEA concentration. Sixteen percent of 600 patients without recurrence showed a false-positive test result. Carcinoembryonic antigen testing was most sensitive for hepatic or retroperitoneal metastasis and relatively insensitive for local, pulmonary, or peritoneal involvement. Surgical explorations were performed in 115 patients with CEA elevations, and 47 recurrences, usually hepatic, were resected with curative intent. On the other hand, 38 patients with normal CEA concentrations and 23 patients not monitored also underwent such resections--usually for pulmonary or local recurrence. Of all CEA-monitored patients, 2.3% are alive and disease free more than 1 year after salvage surgery (2.9% of those with CEA elevations and 1.9% of those with no elevations). Of patients with no CEA monitoring, 2.0% are also alive and disease free more than 1 year after salvage surgery. CONCLUSIONS: Cancer cures attributable to CEA monitoring are, at best, infrequent. It is questionable whether this small gain justifies the substantial cost in dollars and physical and emotional stress that this intervention may cause for patients.

Biomarkers, Tumor↗

A phase II trial of piroxantrone in adenocarcinoma of the pancreas. A Southwest Oncology Group study.

Thirty-five evaluable patients with advanced adenocarcinoma of the pancreas were treated with piroxantrone at a dose of 150 mg/m2 intravenously every 21 days. No objective responses were observed (95% confidence interval 0%-10%). Toxicities of grade > or = 3 were primarily hematologic and were seen in 28 patients. Piroxantrone is inactive in pancreatic cancer and no further investigation of this agent in this tumor is recommended.

Adenocarcinoma↗

VM-26 in gastric cancer. A Southwest Oncology Group study.

The Southwest Oncology Group conducted a trial of VM-26 (teniposide) in patients with advanced gastric cancer. VM-26 60 mg/m2 i.v. infusion over 30-45 minutes was given daily for 5 days every 21 days. Twenty-one eligible patients with measurable disease and a SWOG performance status of 0-2 were analyzed for response and toxicity. Partial responses were seen in 2 of the 21 eligible patients (9.5%). Median survival was 3.8 months. Severe of life-threatening toxicity was observed in 13/21 (62%) patients. This included two drug related deaths related to neutropenic sepsis and seven other patients with grade 4 granulocytopenia (< 500/mm3). Liver dysfunction and hypotension were seen less often and were not dose limiting. Although the modest activity seen was comparable to that of VP-16 (etoposide) as a single agent, the hematologic toxicity observed in this trial would likely preclude further trials of VM-26 (teniposide) in advanced gastric cancer.

Adult↗

Phase II trial of chlorozotocin and fluorouracil in islet cell carcinoma: a Southwest Oncology Group study.

PURPOSE: A phase II trial that used fluorouracil (5-FU) and chlorozotocin (CTZ) was performed in patients with metastatic islet cell carcinoma to determine the response rate and toxicity. PATIENTS AND METHODS: Patients received four cycles of induction chemotherapy. Good-risk patients received 5-FU 800 mg/m2/d days 1 to 4 as a continuous intravenous (IV) infusion (CIV) and CTZ 175 mg/m2 IV on day 1. Poor-risk patients (previous radiation to > or = 25% bone marrow-bearing areas; serum bilirubin > or = 5 mg/dL; creatinine > 1.0 mg/dL) received 5-FU 600 mg/m2/d and CTZ 75 mg/m2 in a similar manner. In responding or stable patients, reduced doses of 5-FU and CTZ were continued as maintenance therapy (maximum, 18 months). RESULTS: Forty-seven of 51 patients were eligible, and 44 received chemotherapy. Fourteen of 44 patients had partial responses, with 13 of 36 (36%; 95% confidence interval [CI], 21.0% to 54.0%) good-risk patients and one of eight (12%; 95% CI, 0.3 to 52.6%) poor-risk patients responding. Median survival of all patients was 25 months, and the median response duration was 11 months. Side effects were moderate to severe and included myelosuppression and gastrointestinal toxicity. Thirteen patients developed renal toxicity, which was severe or life-threatening in five. This seemed to be related to the administration of cumulative doses of CTZ > or = 1,500 mg. CONCLUSION: These results demonstrate that the combination of 5-FU and CTZ has activity in islet cell carcinoma, but the occurrence of renal toxicity secondary to CTZ may limit the use of this agent.

Adenoma, Islet Cell↗

Physical and pharmacologic restraint of nursing home patients with dementia. Impact of specialized units.

This case-control study of 31 specialized dementia units and 32 traditional units in five states investigated use of physical and pharmacologic restraints among 625 patients with the diagnosis of dementia. Physical restraints were observed in use on 18.1% of dementia unit patients and on 51.6% of comparison unit patients who were out of bed during the day (adjusted odds ratio, 0.283;95% confidence interval, 0.129 to 0.619). Pharmacologic restraints were routinely given to 45.3% of dementia unit patients and 43.4% of comparison unit patients (adjusted odds ratio, 0.950; 95% confidence interval, 0.611 to 1.477). We used multivariate logistic regression to identify residence in a nonspecialized nursing home unit, nonambulatory status, transfer dependency, mental status impairment, hip fracture history, and a high nursing staff-to-patient ratio, which we found to be independent predictors of physical restraint use. Physically abusive behavior, severe mental status impairment, and frequent family visitation were found to be significant predictors of pharmacologic restraint use, while advanced patient age, large nursing home size, and patient nonambulatory status were protective against such use. These results support the conclusion that physical and pharmacologic restraint constitute separate treatment modalities with different risk factors for use, and indicate that specialized dementia units are successful in reducing the use of physical but not pharmacologic restraints.

Aged↗

Phase II trial of amonafide in advanced pancreas cancer. A Southwest Oncology Group study.

Amonafide is a new synthetic anticancer agent whose mechanism of action is through inhibition of macromolecular synthesis as well as DNA intercalation. The Southwest Oncology Group (SWOG) has investigated this drug in a phase II study of pancreas cancer. Thirty-six patients were registered on this study: of these 29 were eligible for response evaluation, and 20 received the two cycles required for making a response assessment. Patients met the standard phase II criteria of no prior chemotherapy, measurable disease and a SWOG performance status of 2 or less. Toxicity, predominantly hematologic with significant neutropenia and thrombocytopenia, was quite severe. Four treatment related deaths were encountered. No responses were seen in thirty-six patients studied. We conclude that this drug is not active against adenocarcinoma of the pancreas.

Adenine↗