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Biomedical subjects

T R Fleming

Publications and source records attributed to T R Fleming.

17 recordsLinked to original sources
PubMed1992

Primary sclerosing cholangitis: refinement and validation of survival models.

The natural history of primary sclerosing cholangitis was studied in 426 patients from five medical centers. The median follow-up time was 3.0 years (range, 0.01-16.6 years); 100 patients had died by the time of last follow-up. Survival analysis (Cox proportional-hazards regression) was used to identify the variables most useful in predicting survival of patients with primary sclerosing cholangitis. Serum bilirubin concentration, histological stage on liver biopsy, age, and the presence of splenomegaly were independent predictors of a high risk of dying. A mathematical model to predict survival of patients with primary sclerosing cholangitis (based on referral values of those predictors) was statistically validated using two methods. Confidence intervals for predicting patient-specific survival probabilities are also presented. This model to predict survival could be used to stratify participants in therapeutic trials, counsel patients and their families, decide on candidacy for and timing of liver transplantation, and provide mathematical controls for evaluating the efficacy of therapies for primary sclerosing cholangitis, including transplantation.

Adult↗
PubMed1992

High incidence of coagualopathy in phase II studies of recombinant tumor necrosis factor in advanced pancreatic and gastric cancers.

This multi-center trial was carried out to assess the therapeutic potential of recombinant tumor necrosis factor (rTNF) as the first form of systemic therapy for advanced carcinomas of gastric and pancreatic origin. To be eligible patients were required to have no overt sign of coagulopathy and hepatic function studies with enzymes less than two times beyond the normal range. Twenty nine patients with gastric cancer and 26 with pancreatic cancer were entered from various institutions in the Southwest Oncology Group with 27 and 22, respectively, meeting eligibility criteria. Drug treatment consisted of rTNF (Genentech) given at a dose of 150 micrograms intravenously for five consecutive days every 3 weeks; 50% dose reduction was made for acute intolerance such as hypotension or severe fever and chills. Although eight patients with gastric cancer and five patients with pancreatic cancer received four or more courses of treatment, no objective antitumor responses were recorded. As in other trials common toxicities of rTNF included nausea and vomiting, chills and fever, hypotension, headache, myalgias, fatigue and malaise. However, in this trial, other toxicities became prominent: four episodes of symptomatic disseminated intravascular clotting occurred among patients with pancreatic cancer. Eleven with this disease and five with gastric cancer manifested laboratory findings of abnormal amounts of fibrin split products, and/or hypofibrinogenemia, and/or thrombocytopenia after treatment began. Other laboratory abnormalities that were commonly encountered included hyperglycemia, hypertriglyceridemia, anemia, neutropenia and an elevation in liver enzymes. We conclude that rTNF does not demonstrate antitumor efficacy against adenocarcinomas of the stomach and the pancreas.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
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 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↗
PubMed1979

Dianhydrogalactitol and radiation therapy. Treatment of supratentorial glioma.

Dianhydrogalactitol was the most active of 177 agents tested against a mouse ependymoblastoma tumor. We conducted a prospectively randomized trial comparing whole-brain irradiation alone vs identical irradiation plus dianhydrogalactitol in 42 patients with grade 3 and 4 supratentorial astrocytomas. Patients receiving dianhydrogalactitol in addition to irradiation had a significantly longer median survival time (67 vs 35 weeks) than did patients receiving only irradiation. The major toxic effect of dianhydrogalactitol is hematologic suppression of a cumulative nature. Dianhydrogalactitol may play an important role (in conjunction with radiation therapy) in the initial treatment of patients with supratentorial glioma. Our data may indicate that the mouse ependymoblastoma system is a useful screen for agents to be used in the treatment of human glioma.

Adult↗
PubMed1979

VP-16, cyclophosphamide, adriamycin and cis-platinum (V:CAP-I) in patients with metastatic adenocarcinoma of the lung.

In an attempt to improve upon the 42% regression rate of the CAP-I regimen in patients with advanced adenocarcinoma of the lung, VP-16 was added to that regimen. VP-16, as a single agent, had a response rate of 12.5% (3/24) In a similar group of patients. The new regimen, V:CAP-I, had a tumor regression rate of 35% (7/20) and an estimated median survival of 171 days. Hence, we were unable to conclude that the addition of VP-16 to the CAP-I regimen statistically improved the regression rate of the CAP-I regimen.

Adenocarcinoma↗
PubMed1979

Evaluation of response criteria in advanced lung cancer.

Because we found it illogical to attempt measurement of nonmeasurable but visible tumors in patients with advanced lung cancer, we devised and used a separate set of response criteria for patients with evaluable, nonmeasurable tumors. Patients with evaluable disease who had obtained a tumor regression after therapy were compared to patients with measurable disease who had obtained a tumor regression according to standard criteria. Among 191 cases evaluated (54% with measurable and 46% with evaluable disease), 59 tumor regressions were found (35 in patients with measurable disease and 24 in patients with evaluable disease). Evaluating regressions in patients with both types of disease, we could not detect statistical differences in regression rates, times to regression, durations of regression or survival. We believe the response criteria used for patients with evaluable, nonmeasurable lung cancer to be valid in assessing response to therapy.

Antineoplastic Agents↗
PubMed1979

Pulmonary resection for metastatic nonosteogenic sarcoma.

Analysis was made of 112 patients who underwent resection of metastatic pulmonary noldules for nonosteogenic sarcoma at the Mayo Clinic from 1950--76. The 5-year post-thoracotomy survival was 29% with a median survival of 18 months. There has been no substantial change between 1950 and 1976 in post-thoracotomy survival among all patients who received this operation here. Prognosis was especially grim (p less than 0.01) for patients with pre-thoracotomy disease-free intervals of less than 12 months, and for those experiencing extrathoracic recurrences vs. further pulmonary recurrent tumor (p = .01) following thoracotomy. The following discriminants were not significantly associated with postthoracotomy survival: age, sex, histology, number of lesions fully excised, or site of lung lesions. We conclude that the therapeutic value of thoracotomy in the treatment of metastatic nonosteogenic sarcomas has not changed here during the past quarter of a century. Whether the recent more common use of thoracotomy in metastatic disease of this type is therapeutically worthwhile cannot be clearly determined from the data available.

Humans↗
PubMed1979

Different chemotherapeutic sensitivities and host factors affecting prognosis in advanced ovarian carcinoma versus minimal residual disease.

Treatment of patients with advanced ovarian carcinoma (stages IIIB and IV) using either cyclophosphamide alone (1 g/m2) or cyclophosphamide (500 mg/m2) plus adriamycin (40 mg/m2) by iv injection every 3 weeks each produced partial regression in approximately one third of the patients. Survival curves and time-to-progression curves for the two regimens were nearly identical in these patients with advanced disease. These same regimens produced different results when used monthly in patients who had minimal residual disease (stages II and IIIA). In patients with minimal residual disease the therapeutic index of the combination regimen was superior to that of cyclophosphamide alone. Prognosis was better overall among patients with minimal residual disease than among patients with advanced disease. Within the minimal-disease group grossly complete excision of tumor prior to chemotherapy was associated with still better prognosis. Among patients with advanced disease, prognosis was significantly better for older patients despite their generally less favorable performance scores. Much of this prognostic superiority appeared to be related to menopausal status and presumably to the depletion of endogenous estrogens in the older patients.

Cyclophosphamide↗
PubMed1979

A multiple testing procedure for clinical trials.

A multiple testing procedure is proposed for comparing two treatments when response to treatment is both dichotomous (i.e., success or failure) and immediate. The proposed test statistic for each test is the usual (Pearson) chi-square statistic based on all data collected to that point. The maximum number (N) of tests and the number (m1 + m2) of observations collected between successive tests is fixed in advance. The overall size of the procedure is shown to be controlled with virtually the same accuracy as the single sample chi-square test based on N(m1 + m2) observations. The power is also found to be virtually the same. However, by affording the opportunity to terminate early when one treatment performs markedly better than the other, the multiple testing procedure may eliminate the ethical dilemmas that often accompany clinical trials.

Clinical Trials as Topic↗
PubMedDate not supplied

Efficacy of nonoxynol 9 contraceptive sponge use in preventing heterosexual acquisition of HIV in Nairobi prostitutes.

OBJECTIVE: To determine the efficacy of the nonoxynol 9 contraceptive sponge in preventing sexual acquisition of the human immunodeficiency virus (HIV). DESIGN: Prospective, randomized placebo-controlled trial. SETTING: Research clinic for prostitutes in Nairobi, Kenya. PATIENTS AND INTERVENTIONS: One hundred thirty-eight HIV-seronegative women were enrolled, of whom 74 were assigned to nonoxynol 9 sponge use and 64 to placebo use. These two groups did not significantly differ with respect to demographic characteristics, sexual practices, or prevalence of genital infections at enrollment, except for a lower number of sex partners per week and a higher initial prevalence of genital ulcers among women assigned to nonoxynol 9 sponge use. Among the 116 women who returned for follow-up, the mean durations of follow-up were 14 and 17 months for the two groups, respectively. MAIN OUTCOME MEASURE: HIV seroconversion. RESULTS: Nonoxynol 9 sponge use was associated with an increased frequency of genital ulcers (relative risk [RR], 3.3; P less than .0001) and vulvitis (RR, 3.3; P less than .0001) and a reduced risk of gonococcal cervicitis (RR, 0.4; P less than .0001). Twenty-seven (45%) of 60 women in the nonoxynol 9 sponge group and 20 (36%) of 56 women in the placebo group developed HIV antibodies. The hazard ratio for the association between nonoxynol 9 sponge use and HIV seroconversion was 1.7 (95% confidence interval [CI], 0.9 to 3.0). Using multivariate analysis to control for the presence of genital ulcers at enrollment, the adjusted hazard ratio for the association between nonoxynol 9 sponge use and seroconversion was 1.6 (95% CI, 0.8 to 2.8). CONCLUSIONS: Genital ulcers and vulvitis occurred with increased frequency in nonoxynol 9 sponge users. We were unable to demonstrate that nonoxynol 9 sponge use was effective in reducing the risk of HIV infection among highly exposed women.

Adult↗