Search PubMed⌕ Search

Biomedical subjects

T R Fleming

Publications and source records attributed to T R Fleming.

At least 55 records · Page 3Linked to original sources
PubMed1992

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↗
PubMed1991

A phase II multi-institutional trial of low-dose N-(phosphonacetyl)-L-aspartate and high-dose 5-fluorouracil as a short-term infusion in the treatment of adenocarcinoma of the pancreas. A Southwest Oncology Group study.

Adenocarcinoma of the pancreas is a highly lethal malignancy and chemotherapy has had little impact on the natural history of this disease. PALA, used to potentiate 5-fluorouracil (5-FU), has been shown to have synergy in vivo and in vitro. Twenty-seven patients were treated with an intravenous push dose of PALA (250 mg/m2) followed 24 hours later with a 24-hour infusion of 5-FU (2600 mg/m2). This regimen was repeated weekly. There was one partial response of 21 eligible patients with an estimated response rate of 5%. Toxicity was severe with one toxic death and four patients experiencing Grade 4 toxicity. 5-Fluorouracil and PALA, given in the schedule described, do not appear to be effective against adenocarcinoma of the pancreas.

Adenocarcinoma↗
PubMed1991

A phase II study of chemotherapy of metastatic colorectal carcinoma with 5-fluorouracil plus cisplatin. A Southwest Oncology Group study.

The combination of 5-fluorouracil and cisplatin has shown encouraging results in single institution pilot studies in colorectal carcinoma. This phase II SWOG study was undertaken to further evaluate this treatment. Cisplatin was administered at a dose of 60 mg/M2 IV day 1, repeated every 21 days. 5-FU was given at a dose of 15 mg/Kg IV days 1, 8, and 15, with cycles repeated every 21 days. Among 47 eligible patients there were no complete responses and only three partial responses for an overall response rate of 6% with a 95% confidence interval of 1% to 18%. Seventeen patients (36%) had stable disease/no response and 22 (47%) progressed. Five patients (10%) had no evaluation and were assumed to have had no response, or were early deaths. Median survival was 9.1 months. Significant hematologic toxicity was seen with grade 3 leukopenia occurring in 11 patients. There were felt to be two deaths definitely related to treatment and two additional deaths possibly treatment related. The combination of 5-FU and cisplatin used in this dose and schedule is an ineffective and toxic regimen for treatment of colorectal carcinoma.

Adenocarcinoma↗
PubMed1990

Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma.

Twelve hundred ninety-six patients with resected colon cancer that either was locally invasive (Stage B2) or had regional nodal involvement (Stage C) were randomly assigned to observation or to treatment for one year with levamisole combined with fluorouracil. Patients with Stage C disease could also be randomly assigned to treatment with levamisole alone. The median follow-up time at this writing is 3 years (range, 2 to 5 1/2). Among the patients with Stage C disease, therapy with levamisole plus fluorouracil reduced the risk of cancer recurrence by 41 percent (P less than 0.0001). The overall death rate was reduced by 33 percent (P approximately 0.006). Treatment with levamisole alone had no detectable effect. The results in the patients with Stage B2 disease were equivocal and too preliminary to allow firm conclusions. Toxic effects of levamisole alone were infrequent, usually consisting of mild nausea with occasional dermatitis or leukopenia, and those of levamisole plus fluorouracil were essentially the same as those of fluorouracil alone--i.e., nausea, vomiting, stomatitis, diarrhea, dermatitis, and leukopenia. These reactions were usually not severe and did not greatly impede patients' compliance with their regimen. We conclude that adjuvant therapy with levamisole and fluorouracil should be standard treatment for Stage C colon carcinoma. Since most patients in our study were treated by community oncologists, this approach should be readily adaptable to conventional medical practice.

Adolescent↗
PubMed1990

Phase II evaluation of esorubicin (4'deoxydoxorubicin) in pancreatic adenocarcinoma: a Southwest Oncology Group study.

Esorubicin (4' deoxydoxorubicin) is a new analogue of the anthracycline, doxorubicin. This compound lacks the hydroxyl group at 4' position on the amino sugar of the anthracycline. Phase II study was designed to determine the clinical response rate and to define the qualitative and quantitative toxicities of esorubicin in patients with adenocarcinoma of the pancreas. Fifty-eight patients with inoperable adenocarcinoma of the pancreas were entered on the study, 47 were evaluable for response, and 57 were evaluable for toxicity. The dose of esorubicin was 30 mg/m2 for good risk patients and 25 mg/m2 for poor risk patients every 21 days and administered IV push through a side arm of a running IV. Diphenhydramine, 50 mg is administered IM prior to the administration of the drug to block local venous reaction. Subsequent doses of esorubicin were modified according to granulocyte and platelet nadirs and the drug was not administered until recovery of platelets (greater than 100,000/microliters) and wbc (greater than 3000/microliters). Three partial responses, 20 stable, and 31 with increased disease were observed. Forty-seven had severe granulocytopenia (less than 250), and two patients had severe thrombocytopenia (less than 25,000). One patient experienced a decrease in left ventricular ejection fraction with a total dose of 180 mg/m2. The dose of esorubicin in this study demonstrated that the drug has minimal activity in adenocarcinoma of the pancreas but the toxicity is tolerable. Search should continue for single agents with activity in this disease.

Adenocarcinoma↗
PubMed1990

VM-26 in colorectal carcinoma: a Southwest Oncology Group study.

In this multi-institutional phase II study, VM-26 or Teniposide was administered to forty-two patients with advanced colorectal cancer. Patients were initially treated at 60 mg/M2 daily for 5 days with dose adjustments depending on toxicity. One complete response and one partial response were observed lasting six and four months respectively. Leukopenia was severe in 40% of patients. No drug related deaths were seen. In this Southwest Oncology Group (SWOG) study, VM-26 appeared to have minimal benefit in advanced colorectal cancer.

Colorectal Neoplasms↗
PubMed1990

Phase II evaluation of recombinant gamma-interferon in patients with advanced pancreatic carcinoma: a Southwest Oncology Group study.

Thirty evaluable patients with advanced carcinoma of the pancreas received treatment with either daily x 5 bolus or continuous infusion x 5 days recombinant gamma-interferon. No responses were noted. Major toxicities included fever, hypotension, and flu-like symptoms. gamma-Interferon does not appear to be an active single agent for patients with advanced pancreatic cancer.

Aged↗
PubMed1990

Interim analyses in clinical trials.

Clinical trials of new cancer treatments often involve multiple analyses of the data to address concerns related to medical ethics and the costs and efficiency of medical research. Failure to account for such interim analyses can introduce significant bias into the results of a study. The authors discuss the role of interim analyses in clinical trials and describe the factors that need to be considered in the planning, monitoring, and reporting of a study involving group sequential hypothesis tests.

Bias↗
PubMed1990

Evaluation of active control trials in AIDS.

In settings in which effective standard treatment exists, active control trials provide an ethically appealing approach to evaluating experimental therapies by allowing all patients to be randomized either to a promising new regimen or to the standard as it would be routinely delivered in clinical practice. This paper describes an appropriate statistical approach for analyzing the clinical efficacy of new treatments in such studies. Confidence intervals for the relative efficacy of the new treatment vis-à-vis standard therapy are used to provide information required to determine whether the experimental treatment has an improved therapeutic index. Desirable properties of this approach include the ability to implement standard group sequential guidelines for early trial termination, the ability to use valid surrogates for hard clinical outcomes, and the availability of straightforward formulas for sample size calculations.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Efficacy of liver transplantation in patients with primary biliary cirrhosis.

No controlled trials have been performed to assess the efficacy of liver transplantation. Because of the marked improvement in survival after liver transplantation since 1981, random assignment of patients to a control group not undergoing transplantation is considered clinically inappropriate. To assess the efficacy of liver transplantation in patients with primary biliary cirrhosis, we compared survival in 161 patients with this diagnosis who had undergone a liver transplantation with survival in patients with the same diagnosis who had been treated conservatively. The comparison was performed with use of a recently developed statistical technique, the Mayo model. All patients had undergone liver transplantation between March 1980 and June 1987 and were followed for a median of 25 months. Three months after liver transplantation, the Kaplan-Meier survival probabilities in the recipients were substantially higher than the Mayo-model "simulated-control" survival probabilities (P less than 0.001). At two years, the Kaplan-Meier survival probability was 0.74, whereas the mean Mayo-model survival probability was 0.31. The patients who were at low risk according to the Mayo model had the best probability of survival after liver transplantation; however, patients at all risk levels who had undergone liver transplantation had higher probabilities of survival that those who had not. We conclude that liver transplantation is an efficacious treatment in patients with advanced primary biliary cirrhosis.

Follow-Up Studies↗
PubMed1989

Approaches to monitoring clinical trials.

In prospective clinical trials, safety and efficacy results should be monitored periodically. If early data provide convincing evidence of a superior therapeutic index for one of the treatments, then early trial termination would satisfy important ethical requirements and save valuable resources and time. The data obtained in these studies are often analyzed further to determine whether treatment effects differ in various subsets. In this paper we discuss the problems that can arise from frequently used inappropriate approaches to interim and subset analyses. The proper role of such analyses is then discussed, and valid and useful methods are described for deciding on early termination of negative as well as positive studies and for investigating subset effects.

Clinical Trials as Topic↗
PubMed1989

Prognosis in primary biliary cirrhosis: model for decision making.

The ideal mathematical model for predicting survival for individual patients with primary biliary cirrhosis should be based on a small number of inexpensive, noninvasive measurements that are universally available. Such a model would be useful in medical management by aiding in the selection of patients for and timing of orthotopic liver transplantation. This paper describes the development, testing and use of a mathematical model for predicting survival. The Cox regression method and comprehensive data from 312 Mayo Clinic patients with primary biliary cirrhosis were used to derive a model based on patient's age, total serum bilirubin and serum albumin concentrations, prothrombin time and severity of edema. When cross-validated on an independent set of 106 Mayo Clinic primary biliary cirrhosis patients, the model predicted survival accurately. Our model was found to be comparable in quality to two other primary biliary cirrhosis survival models reported in the literature and to have the advantage of not requiring liver biopsy.

Decision Making, Computer-Assisted↗
PubMed1989

Primary sclerosing cholangitis: natural history, prognostic factors and survival analysis.

The natural history of primary sclerosing cholangitis was assessed in 174 patients; 37 were asymptomatic and 137 had symptoms related to underlying liver disease. At the time of diagnosis, the mean age was 39.9 years, 66% of the primary sclerosing cholangitis patients were male and 71% had associated inflammatory bowel disease, most commonly chronic ulcerative colitis. Long-term follow-up (mean: 6.0 years; range: 2.7 to 15.5 years) was available in all patients. During follow-up, 59 (34%) of the patients died: 55 in the symptomatic group and four in the asymptomatic group. Median survival from the time of diagnosis of primary sclerosing cholangitis at the Mayo Clinic was 11.9 years. Survival in the asymptomatic group was significantly decreased compared with that in a control population matched for age, race and sex. Multivariate analysis (Cox proportional hazards regression modeling) revealed that age, serum bilirubin concentration, blood hemoglobin concentration, presence or absence of inflammatory bowel disease and histologic stage on liver biopsy were independent predictors of high risk of dying. The development of a multivariate statistical survival model is a major step in identifying individual primary sclerosing cholangitis patients at low, moderate and high risk of dying. Such models will be useful for stratifying patients in therapeutic trials, in patient counseling and in patient selection and timing of liver transplantation.

Adult↗
PubMed1989

Extramural cross-validation of the Mayo primary biliary cirrhosis survival model establishes its generalizability.

The generalizability of the Mayo model for predicting survival in individual primary biliary cirrhosis patients without liver transplantation was tested and confirmed. The model was applied to a data base of patients from the New England Medical Center Hospitals (n = 141) and the Scott and White Clinic (n = 35) and found to predict their survival accurately. It was also shown to be accurate for Mayo primary biliary cirrhosis patients with very advanced disease (n = 30), those with less than a 33% chance of surviving 12 months. The analyses confirmed that the addition of histologic stage did not significantly improve the predictive power of the model (p greater than 0.10). We suggest that the Mayo model is a practical tool for clinical management and decision making.

Academic Medical Centers↗
PubMed1989

Surgical adjuvant therapy of large-bowel carcinoma: an evaluation of levamisole and the combination of levamisole and fluorouracil. The North Central Cancer Treatment Group and the Mayo Clinic.

A total of 401 eligible patients with resected stages B and C colorectal carcinoma were randomly assigned to no-further therapy or to adjuvant treatment with either levamisole alone, 150 mg/d for 3 days every 2 weeks for 1 year, or levamisole plus fluorouracil (5-FU), 450 mg/m2/d intravenously (IV) for 5 days and beginning at 28 days, 450 mg/m2 weekly for 1 year. Levamisole plus 5-FU, and to a lesser extent levamisole alone, reduced cancer recurrence in comparison with no adjuvant therapy. These differences, after correction for imbalances in prognostic variables, were only suggestive for levamisole alone (P = .05) but quite significant for levamisole plus 5-FU (P = .003). Whereas both treatment regimens were associated with overall improvements in survival, these improvements reached borderline significance only for stage C patients treated with levamisole plus 5-FU (P = .03). Therapy was clinically tolerable with either regimen and severe toxicity was uncommon. These promising results have led to a large national intergroup confirmatory trial currently in progress.

Adult↗
PubMed1989

Symmetric group sequential test designs.

In Phase III clinical trials, ethical considerations often demand interim analyses in order that the better treatment be made available to all patients as soon as possible. Group sequential test designs that do not treat the hypotheses symmetrically may not fully address this concern since early termination of the study may be easier under one of the hypotheses. We present a one-parameter family of symmetric one-sided group sequential designs that are nearly fully efficient in terms of the average sample number. The symmetric tests are then extended to a two-sided hypothesis test. These symmetric two-sided group sequential tests are found to have improved overall efficiency when compared to the tests proposed by Pocock (1977, Biometrika 64, 191-199) and O'Brien and Fleming (1979, Biometrics 35, 549-556). Tables of critical values for both one-sided and two-sided symmetric designs are provided, thus allowing easy determination of sample sizes and stopping boundaries for a group sequential test. Approximate tests based on these designs are proposed for use when the number and timing of analyses are random.

Clinical Trials as Topic↗