Search PubMed⌕ Search

Biomedical subjects

J Fiore

Publications and source records attributed to J Fiore.

15 recordsLinked to original sources
PubMed2000

Phase I chemotherapy study of biochemical modulation of folinic acid and fluorouracil by gemcitabine in patients with solid tumor malignancies.

PURPOSE: This phase I biochemical modulation study evaluated the maximum-tolerated dose (MTD), toxicity, and effectiveness of the combination of folinic acid (FA)/fluorouracil (5-FU) followed by escalated dose levels of gemcitabine (FFG) in patients with advanced solid tumors. PATIENTS AND METHODS: Patients were refractory to primary treatment and/or without effective treatment options. Twenty-eight patients received an intravenous (IV) infusion of FA 100 mg/m(2) over 1 hour and a 5-FU 450 mg/m(2) IV bolus in the middle of the FA infusion. After the FA infusion, gemcitabine was administered at a steady rate of infusion of 10 mg/m(2)/min over initially 30 minutes and with increases of an additional 15 minutes at each given level. One cycle consisted of six weekly treatments followed by a 2-week rest. RESULTS: The MTD of gemcitabine was established at 900 mg/m(2) given over 90 minutes. Eight patients of 21 with metastatic colorectal cancer achieved responses (one complete response; seven partial responses), for a response rate of 38%. Responses were seen across the gemcitabine doses of 300 to 900 mg/m(2). One patient had prior treatment with FA/5-FU for advanced disease. Patients with colorectal carcinoma had a median survival of 18 months, and the patient with lung carcinoma has been alive for 24+ months. CONCLUSION: The combination chemotherapy of FFG was well tolerated and may benefit patients with advanced colorectal carcinoma. A phase II evaluation in this patient population is in progress.

Adult↗
PubMed1996

Random regression with imputed values for dropouts.

The random regression model (RRM) has been advocated as a potential solution to problems of statistical analysis posed by dropouts in clinical trials. However, the power of the RRM tests for differences in rates of change can be seriously attenuated by presence of dropouts. The use of imputed scores and other modifications are examined in an attempt to render a simple growth-curve form of the RRM analysis more robust against dropouts. Methods that extrapolate from an individual's own performance were found effective, although inclusion of time-in-treatment as a covariate was documented to be important under identifiable conditions. Of the methods evaluated, those that used group data to impute missing values for dropouts produced nonconservative bias. The results suggest the importance of careful evaluation of potential bias when integrating any group-based imputation procedure into the RRM analyses.

Clinical Trials as Topic↗
PubMed1995

Preclinical and clinical evaluation of 5-fluorouracil biochemical modulation with folinic acid and hydroxyurea for patients with colorectal carcinoma.

BACKGROUND: Approximately 140,000 new cases of colorectal carcinoma will be diagnosed in 1995 in the United States, and more than one-third of these patients will die from progressive disease. Despite the modest improvement in response rate with chemotherapy, little improvement in patient survival has been noted. Consequently, the evaluation of new agents, modalities, and combinations is needed. METHODS: Two cell lines, HCT 116 and COLO 320 HSR, were treated with various concentrations of 5-fluorouracil (5-FU), folinic acid (FA), and hydroxyurea (HU). Subsequently, 41 patients with advanced, measurable metastatic colorectal carcinoma were enrolled in the study. Patients were treated with oral doses of HU (500 mg) every 8 hours on Days 1 and 2, 5-FU (400-500 mg/m2) intravenously Day 2 and FA (100 mg/m2) intravenously on Day 2 of every week for 6 consecutive weeks, followed by a 2-week rest period. All patients were evaluable for toxicity, and 40 were evaluable for response. RESULTS: In both cell lines, the combination of 5-FU/FA/HU consistently produced the best cytotoxic effect. Clinically, the maximum tolerated dose of 5-FU was established at a level of 500 mg/m2 (450 mg/m2 for patients older than 70 years of age). Ten patients experienced Grade 3 or 4 toxicity, consisting mainly of diarrhea. Eleven of 40 evaluable patients responded (three complete responses, eight partial responses), with a median survival of 12+ months and time to progression of 8.5+ months. CONCLUSION: The biochemical modulation of 5-FU with FA and HU were significantly effective in treating patients with metastatic colorectal carcinoma. Overall, this regimen was well tolerated with only moderate toxicity. Further studies incorporating intravenous HU as well as a randomized Phase III study of 5-FU/FA/HU versus 5-FU/FA are recommended.

Antimetabolites, Antineoplastic↗
PubMed1994

Apparent selection against transmission of zidovudine-resistant human immunodeficiency virus type 1 variants.

The sexual transmission of zidovudine-resistant human immunodeficiency virus type 1 (HIV-1) variants was investigated in 5 donor-recipient pairs in which all donors and none of the recipients had received zidovudine treatment. The virus isolates were tested for sensitivity to zidovudine (IC50) in vitro using blood donor lymphocytes. A region of the HIV-1 pol gene was also directly sequenced by a solid-phase sequencing method. Four donors were shown to have zidovudine-resistant HIV-1 variants. Two of these patients had a single mutation (Thr215-->Tyr), and 2 had a double mutation (Met41-->Leu and Thr215-->Tyr) that previously has been shown to confer zidovudine resistance. Zidovudine-resistant virus was found in only 1 of the 4 recipients, which indicates that zidovudine-resistant HIV-1 variants may be selected against during transmission. Thus, the transmission of zidovudine-resistant HIV-1 variants is a complex process that will require consideration whenever zidovudine treatment is initiated in persons who may have been infected by resistant variants.

Adult↗
PubMed1990

Metastatic adenocarcinomas of unknown primary site. Prognostic variables and treatment results.

As part of a Phase II chemotherapy trial using mitomycin-C, adriamycin, and vindesine, 57 patients with adenocarcinoma of unknown primary site were assessed for prognostic variables predictive of response and survival. They were also evaluated for response and toxicity, usefulness of screening techniques, and eventual definition of primary site and pattern of progression. Only gender predicted response, with women being more likely to respond than men. Visceral metastases below the diaphragm, or the presence of liver metastases, predicted poor survival. Responding patients were highly likely to relapse first at sites of initial disease. Hemolytic-uremic syndrome was the most severe toxicity; other side effects were moderate. The response rate was 30% (three complete responders), which is similar to other current regimens. This study suggests that patients with better prognosis characteristics of single site of disease and without intraabdominal tumor may benefit from a policy of expectant observation after local control has been established. Patients with multiple sites of disease and/or intraabdominal tumor are appropriate candidates for investigational chemotherapy.

Adenocarcinoma↗
PubMed1989

Protein A immunotherapy in the treatment of cancer: an update.

Protein A, a naturally occurring Staphylococcus aureus cell surface protein, has the unusual property of binding circulating immune complexes and immunoglobulin G with high avidity. CIC have played a major role in cancer-associated immunosuppression. Thus, removal of the immunosuppressive agents, ie, the CIC, may lead to a modulation of the immunosuppression and a liberation of the immune system to perform an antitumor effect. In animal studies, protein A has been used in extracorporeal immunoadsorption columns and treatments have resulted in tumor shrinkage and antiviral responses. Our group developed a multicenter clinical trial to assess toxicity and antitumor responses with this biologic response modifier alone. This is an update of our original trial. We have now treated 142 patients for a total of 1,306 treatments. The patients consisted of 74 males and 68 females. Their age ranged from 7 to 83 years, with a mean of 50 years. The Karnofsky performance index values ranged from 40 to 95, with a mean of 80. Patients who received seven or more treatments were considered eligible for tumor response assessment, and all patients with one or more treatments were eligible for toxicity assessment. Thus, there were 101 patients eligible for tumor response and 142 eligible for toxicity response. The total response rate was 22 patients or 21.8% (partial remission [PR], 12 patients, 12%; less than PR, 10 patients, 10%). Response rates were similar in the 13 treatment centers. Toxicity was assessed in 142 patients. One thousand three hundred six treatments were assessed for treatment toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Trials as Topic↗
PubMed1988

Normal G2 chromosomal radiosensitivity and cell survival in the cancer family syndrome.

Recent reports have suggested that elevated chromosomal aberration yields following X-irradiation of skin fibroblasts in the G2 phase of the cell cycle are characteristic of affected members of cancer-prone families. These studies propose that this phenomenon is a consequence of impaired DNA repair and might be a useful predictor of genetic susceptibility to cancer. We have tested G2 chromosomal X-ray sensitivity in skin fibroblasts and peripheral blood lymphocytes from members of a kindred with the cancer family syndrome, a disorder in which susceptibility to colon cancer and other epithelial cancers is inherited in an autosomal dominant pattern. Further, using a cell survival assay, we tested cancer family syndrome skin fibroblasts for sensitivity to four classes of mutagens, including X-rays. In the assays used, skin fibroblasts and lymphocytes from both affected and unaffected family members exhibited responses indistinguishable from normal controls. Karyotypic analysis of lymphocytes and fibroblasts revealed no consistent constitutional cytogenetic abnormality. Thus, affected patients with the cancer family syndrome do not have increased sensitivity to irradiation and chemical mutagens and lack a germ-line chromosomal defect.

Cell Survival↗
PubMed1988

Protein A immunoadsorption in the treatment of malignant disease.

Circulating immune complexes (CIC) are known to be present in cancer patients and are responsible for much of the cancer-associated immunosuppression. Removal or modulation of these "blocking factors" can reverse the immunosuppression. Protein A from Staphylococcus aureus has the unusual property of binding to CIC with high avidity. Use of protein A as an immunoadsorbent in extracorporeal immunotherapy affinity columns has resulted in antitumor and antiviral responses in animals. Our group developed a multicenter trial to assess toxicity and antitumor response with this biologic response modifier alone. Overall, 24% (21 of 87 patients) had objective tumor regressions including both partial responses (PR) and less than PR. No complete responses (CR) were observed. Responses were observed in acquired immune deficiency syndrome (AIDS)-related Kaposi's sarcoma (six of 17 PR; two of 17 less than PR; overall, 47%), breast adenocarcinoma (five of 22 PR; three of 22 less than PR; overall response, 36%), colon adenocarcinoma, (one PR, one less than PR; overall response, 11%), and non-oat cell lung carcinoma (two of seven less than PR). The procedure was well tolerated and could be performed on an outpatient basis. No adverse reaction was observed in 735 of 1,113 treatments (66%). The most common adverse effect was an "influenza-like" syndrome consisting of fever and chills. Pain was present in 12% of the patients. There were no study-related deaths. Serum IgG and CIC levels did not statistically change due to therapy in responding or nonresponding patients. Complement levels remained within the normal range. Liver and renal tests remained stable throughout the study. In summary, protein A immunoadsorption of plasma is well tolerated in the outpatient clinic, has demonstrated antitumor activity in resistant solid tumors, and functions as a biologic response modifier.

Adolescent↗
PubMed1987

Phase II trial of etoposide in APUD tumors.

Thirty-three patients with advanced, metastatic APUD tumors (islet cell, carcinoid, or medullary carcinomas of the thyroid) were treated with etoposide as a single agent. Of 29 evaluable patients, four (14%) had partial responses (95% confidence limits, 1%-26%). Toxic effects seen were those previously reported for etoposide as a single agent. Etoposide has activity in APUD tumors; further studies with this agent are indicated.

Adenoma, Islet Cell↗
PubMed1986

Social support as a multifaceted concept: examination of important dimensions for adjustment.

Four commonly used operationalizations of the social support concept: network contact frequency, satisfaction with support (including nine dimensions), perceived availability of support, and use of support, were related to two measures of psychological adjustment (Beck Depression Inventory and Symptom Checklist-90) and to one measure of physical adjustment (Cornell Medical Index). Subjects were 68 45- to 85-year-old, highly stressed care-givers to spouses with Alzheimer's disease. Results indicate that of the four operationalizations, Satisfaction with Support was the only significant predictor of depression and general psychopathology. The set of four support variables showed the strongest relationship to depression level, next strongest to general psychopathology, and least to physical health. The satisfaction with nine social support dimensions related differentially to the types of adjustment. Results suggest the importance of specificity (sample, support operationalization, dimensions, adjustment measures) in social support research.

Adaptation, Psychological↗
PubMed1983

Social network interactions: a buffer or a stress.

Forty-four caregivers to spouses with a diagnosis of Alzheimer's disease provided a stressed subject population considered at high risk for depression. Unlike more typical unidirectional measures of perceived social support quality, subject ratings were elicited separately as to how helpful as well as how upsetting each network member was in five different support categories. Correlations between perceived network "upset" and depression (Beck Depression Inventory) were highly significant, while in no case did perceived "helpfulness" relate to depression. Using stepwise multiple regression, the set of five support category Upset ratings predicted depression better than did helpful/upset ratios, which in turn predicted depression better than the Helpfulness ratings as a group. The implications of these findings for the conceptualization of social support and its measurement are discussed.

Adjustment Disorders↗
PubMedDate not supplied

Acute hemodynamic effects of tocainide in patients undergoing cardiac catheterization.

To characterize the acute hemodynamic effects of tocainide hydrochloride, a new antiarrhythmic agent, 11 patients undergoing diagnostic cardiac catheterization were given intravenous infusions of the drug for 15 minutes at rates of 0.50 (six patients) or 0.75 (five patients) mg/kg/min. The hemodynamic status of these subjects was determined before, during, and for 15 minutes after treatment, and blood levels of tocainide were followed during and after treatment. Tocainide blood levels at the end of the infusions were 14.9 +/- 1.6 microgram/ml (S.E.) and 15 minutes later were 6.0 +/- 0.7 microgram/ml. In these subjects treatment was not associated with significant changes in Ao or PCW, but it was associated with a statistically significant but small decrease in LV dp/dt. At the same time, LVED was not significantly elevated. Treatment was also accompanied by small increases in PA diastolic and mean pressures, but RA and RV were unchanged. Significant changes were not seen in HR, CO, CI, SV, SVR, or PVR. Thus, the intravenous infusion of 0.50 and 0.75 mg/kg/min of tocainide for 15 minutes produced small but statistically significant depression of left ventricular function without producing changes in CO or clinical evidence of congestive heart failure.

Adult↗