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Biomedical subjects

M Seymour

Publications and source records attributed to M Seymour.

At least 19 recordsLinked to original sources
PubMed2006

Cost-effectiveness of oxaliplatin and capecitabine in the adjuvant treatment of stage III colon cancer.

For many years, the standard treatment for stage III colon cancer has been surgical resection followed by 5-fluorouracil in combination with folinic acid (5-FU/LV). Ongoing clinical trial evidence suggests that capecitabine and oxaliplatin (in combination with 5-FU/LV) may improve disease-free survival and overall survival when compared against 5-FU/LV alone in the adjuvant setting. This study evaluates the cost-effectiveness profiles of these two regimens in comparison to standard chemotherapy, using evidence from two international randomised controlled trials. Survival modelling techniques were employed to extrapolate survival curves from the two trials in order to estimate the long-term benefits of alternative treatment options over the remaining lifetime of patients. The health economic analysis suggests that capecitabine is expected to produce greater health gains at a lower cost than 5-FU/LV. Oxaliplatin in combination with 5-FU/LV is estimated to cost pounds 2970 per additional QALY gained when compared to 5-FU/LV alone. Future research should attempt to elucidate uncertainties concerning the optimal roles of capecitabine and/or oxaliplatin in the adjuvant setting in order to achieve the maximum level of clinical benefit.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Efficacy and tolerability of chemotherapy in elderly patients with advanced oesophago-gastric cancer: A pooled analysis of three clinical trials.

The aim of this study was to determine the benefits of chemotherapy for oesophago-gastric cancer (OGC) in patients 70 years and above (> or =70) in comparison to younger patients. 1080 patients were enrolled into three randomised controlled trials assessing fluorouracil-based combination chemotherapy. Patients received either a platinum-containing regimen (ECF, MCF), PVI 5-FU (protracted venous infusion of 5-fluorouracil)+/-mitomycin C (MMC), or FAMTX. Of the 1080 patients randomised, 257 (23.8%) were aged > or =70 years. There were no significant differences in the incidence of grades 3/4 toxicity between the two cohorts. Objective and symptomatic response rates, failure-free and overall survival were not significantly different. In a multivariate analysis, independent prognostic factors for survival were performance status and locally advanced disease, not age. Patients > or =70 years with OGC obtained similar benefits from palliative chemotherapy with respect to symptomatic response, tumour regression and survival, without increased toxicities.

Aged↗
PubMed2003

A randomised study of protracted venous infusion of 5-fluorouracil (5-FU) with or without bolus mitomycin C (MMC) in patients with carcinoma of unknown primary.

No standard regimen has been identified for patients with a carcinoma of unknown primary (CUP). This study compared protracted venous infusion 5-fluorouracil (PVI 5-FU) with or without mitomycin C (MMC) in patients with CUP in a multicentre, prospectively randomised study. 88 patients were randomised to PVI 5-FU (300 mg/m(2)/day for a maximum of 24 weeks) +/-MMC (7 mg/m(2) 6 weekly for four courses). The overall response rate was 11.6% for PVI 5-FU alone compared with 20.0% for PVI 5-FU plus MMC (P=0.29). Median failure-free survival (FFS) was 4.1 months for PVI 5-FU and 3.6 months for PVI 5-FU plus MMC (P=0.78) with an equivalent overall survival (OS) (6.6 versus 4.7 months, P=0.60). Symptomatic benefit was observed in most patients in each arm. PVI 5-FU is a well tolerated outpatient treatment regimen for patients with CUP, although the addition of MMC provides little extra benefit. PVI 5-FU may be a potential reference regimen in randomised trials with newer chemotherapy agents in patients with CUP.

Adult↗
PubMed2002

Prospective randomized trial comparing mitomycin, cisplatin, and protracted venous-infusion fluorouracil (PVI 5-FU) With epirubicin, cisplatin, and PVI 5-FU in advanced esophagogastric cancer.

PURPOSE: We report the results of a prospectively randomized study that compared the combination of epirubicin, cisplatin, and protracted venous-infusion fluorouracil (PVI 5-FU) (ECF) with the combination of mitomycin, cisplatin, and PVI 5-FU (MCF) in previously untreated patients with advanced esophagogastric cancer. PATIENTS AND METHODS: Five hundred eighty patients with adenocarcinoma, squamous carcinoma, or undifferentiated carcinoma were randomized to receive either ECF (epirubicin 50 mg/m(2) every 3 weeks, cisplatin 60 mg/m(2) every 3 weeks and PVI 5-FU 200 mg/m(2)/d) or MCF (mitomycin 7 mg/m(2) every 6 weeks, cisplatin 60 mg/m(2) every 3 weeks, and PVI 5-FU 300 mg/m(2)/d) and analyzed for survival, response, toxicity, and quality of life (QOL). RESULTS: The overall response rate was 42.4% (95% confidence interval [CI], 37% to 48%) with ECF and 44.1% (95% CI, 38% to 50%) with MCF (P =.692). Toxicity was tolerable, and there were only two toxic deaths. ECF resulted in more grade 3/4 neutropenia and grade 2 alopecia, but MCF caused more thrombocytopenia and plantar-palmar erythema. Median survival was 9.4 months with ECF and 8.7 months with MCF (P =.315); at 1 year, 40.2% (95% CI, 34% to 46%) of ECF and 32.7% (95% CI, 27% to 38%) of MCF patients were alive. Median failure-free survival was 7 months with both regimens. Global QOL scores were better with ECF at 3 and 6 months. CONCLUSION: This study confirms response, survival, and QOL benefits of ECF observed in a previous randomized study. The equivalent efficacy of MCF was demonstrated, but QOL was superior with ECF. ECF remains one of the reference treatments for advanced esophagogastric cancer.

Adult↗
PubMed2002

A multicentre, randomised phase III trial comparing protracted venous infusion (PVI) 5-fluorouracil (5-FU) with PVI 5-FU plus mitomycin C in patients with inoperable oesophago-gastric cancer.

BACKGROUND: This randomised study compared protracted venous infusion (PVI) fluorouracil (5-FU) with PVI 5-FU plus mitomycin C (MMC) in patients with advanced oesophago-gastric cancer. PATIENTS AND METHODS: Two hundred and fifty-four patients with adenocarcinoma, squamous cell carcinoma or undifferentiated carcinoma involving the oesophagus, oesophago-gastric junction or the stomach were randomised. The major end points were tumour response, survival, toxicity and quality of life. RESULTS: The median age of patients treated was 72 years and the two arms were well-balanced for baseline demographic factors. The overall response rate was 16.1% [95% confidence interval (CI) 9.5% to 22.7%] in patients treated with PVI 5-FU alone compared with 19.1% (95% CI 12.0% to 26.0%) for those treated with PVI 5-FU plus MMC (P = 0.555). Median time to treatment failure was 3.9 months for PVI 5-FU and 3.8 months for PVI 5-FU plus MMC (P = 0.195). Median survival was 6.3 months for PVI 5-FU and 5.3 months for PVI 5-FU plus MMC (P = 1.0). Toxicity was mild for both treatments. Symptomatic benefit measured by improvement in pain control, weight loss, dysphagia and oesophageal reflux was observed in over 64% of patients in each arm. Quality of life scores were comparable in each arm. CONCLUSIONS: PVI 5-FU is a safe, effective form of palliation for patients with advanced oesophago-gastric cancer although the addition of MMC adds little extra benefit.

Aged↗
PubMed2000

Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer.

PURPOSE: In a previous study of treatment for advanced colorectal cancer, the LV5FU2 regimen, comprising leucovorin (LV) plus bolus and infusional fluorouracil (5FU) every 2 weeks, was superior to the standard North Central Cancer Treatment Group/Mayo Clinic 5-day bolus 5FU/LV regimen. This phase III study investigated the effect of combining oxaliplatin with LV5FU2, with progression-free survival as the primary end point. PATIENTS AND METHODS: Four hundred twenty previously untreated patients with measurable disease were randomized to receive a 2-hour infusion of LV (200 mg/m(2)/d) followed by a 5FU bolus (400 mg/m(2)/d) and 22-hour infusion (600 mg/m(2)/d) for 2 consecutive days every 2 weeks, either alone or together with oxaliplatin 85 mg/m(2) as a 2-hour infusion on day 1. RESULTS: Patients allocated to oxaliplatin plus LV5FU2 had significantly longer progression-free survival (median, 9.0 v 6.2 months; P =.0003) and better response rate (50.7% v 22.3%; P =.0001) when compared with the control arm. The improvement in overall survival did not reach significance (median, 16.2 v 14.7 months; P =. 12). LV5FU2 plus oxaliplatin gave higher frequencies of National Cancer Institute common toxicity criteria grade 3/4 neutropenia (41. 7% v 5.3% of patients), grade 3/4 diarrhea (11.9% v 5.3%), and grade 3 neurosensory toxicity (18.2% v 0%), but this did not result in impairment of quality of life (QoL). Survival without disease progression or deterioration in global health status was longer in patients allocated to oxaliplatin treatment (P =.004). CONCLUSION: The LV5FU2-oxaliplatin combination seems beneficial as first-line therapy in advanced colorectal cancer, demonstrating a prolonged progression-free survival with acceptable tolerability and maintenance of QoL.

Adenocarcinoma↗
PubMed1999

Marimastat in recurrent colorectal cancer: exploratory evaluation of biological activity by measurement of carcinoembryonic antigen.

Marimastat is a specific inhibitor of matrix metalloproteinases that has been shown to be effective in cancer models. A pilot, escalating-dose study of oral marimastat was performed in patients with recurrent colorectal cancer, in whom evaluation of serological response was made by measurement of carcinoembryonic antigen (CEA) levels. The study assessed the safety and tolerability of 4 weeks administration of marimastat, and determined a dose range producing detectable serological effects. Patients were recruited with a serum CEA level greater than 5 ng ml(-1), and rising by more than 25% over a 4-week screening period. Patients were treated for 28 days and entered into a continuation protocol if a serological response or clinical benefit was observed. Pharmacokinetic and safety data determined that groups of patients were recruited sequentially at 25 mg and 50 mg twice daily, and, thereafter, 10 mg twice daily, 10 mg once daily, 5 mg once daily and 20 mg once daily. A biological effect (BE) was defined as a CEA value on day 28 no greater than on day 0; a partial biological effect (PBE) was defined as a rise in CEA over the 28-day treatment period of less than 25%. Of 70 patients recruited, 63 completed the 28-day treatment period, and 55 were eligible for cancer antigen analysis. Examination of the dose-effect relationships provides evidence for a causal relationship between marimastat and biological effects: the proportion of patients with BE or PBE was higher with twice daily dosing (16 out of 25, 64%) than with once daily dosing (11 out of 30, 37%) (P = 0.043, chi2 test). Furthermore, the median rates of rise of CEA fell markedly during treatment compared with the screening period for patients receiving twice daily marimastat (P<0.0001), but not for patients receiving marimastat once daily (P = 0.25). Musculoskeletal adverse events emerged as the principal drug-related toxicity of marimastat, occurring in a dose- and time-dependent fashion. It was concluded that marimastat was associated with dose-dependent biological effects in cancer patients. The occurrence of musculoskeletal side-effects define 25 mg twice daily as the upper limit of the dose range for continuous use in further studies. Therefore, a dose range of 20 mg once daily to 25 mg twice daily seems appropriate for further studies, which should aim to demonstrate the efficacy of the drug in terms of conventional clinical end points and describe the long-term tolerability of this novel agent.

Administration, Oral↗
PubMed1998

Immunoaffinity chromatography combined on-line with high-performance liquid chromatography-mass spectrometry for the determination of corticosteroids.

On-line coupled immunoaffinity chromatography-reversed-phase high-performance liquid chromatography (IAC-HPLC) with detection by quadrupole ion trap mass spectrometry using a particle beam interface has been developed for the determination of the steroids, dexamethasone and flumethasone. HEMA (polyhydroxyethylmethacrylate) was evaluated as a support material for the anti-dexamethasone antibodies used in IAC. Antibody cross-reactivity and non-specific binding have been investigated for the HEMA bound anti-dexamethasone IAC column. The on-line IAC-HPLC-MS determination of dexamethasone and flumethasone in post-administration equine urine samples showed precisions (R.S.D.) of 8.0 and 7.1%, respectively, with limits of detection in the range 3-4 ng/ml.

Adrenal Cortex Hormones↗
PubMed1998

Improved adherence of genetically modified endothelial cells to small-diameter expanded polytetrafluoroethylene grafts in a canine model.

PURPOSE: A significant limitation to using genetically modified endothelial cells (ECs) to seed prosthetic grafts before implantation has been poor cell adherence to the graft lumen. Methodologic changes to improve cell adherence were evaluated in a canine carotid interposition graft model using 4 mm interior diameter expanded polytetrafluoroethylene. METHODS: ECs harvested from external jugular veins were grown in culture, with 80% of the cells from each culture transduced by incubation with an LXSN-type retroviral vector carrying a gene for human prourokinase and a neomycin resistance gene for selection in antibiotic G418. Control grafts had passive luminal coating with fibronectin and were seeded with transduced ECs immediately after G418 selection; these grafts were incubated for 2 days before implantation. Experimental grafts had fibronectin forcefully squeezed through the interstices and were seeded with ECs that had recovered in culture for 5 days after G418 selection; these grafts were incubated for 4 days before implantation. For each control (n = 9) and experimental (n = 12) graft, a graft prepared in the same fashion but seeded with the remaining autologous nontransduced cells was placed in the contralateral carotid artery. Grafts were explanted after 30 days and were evaluated for patency, thrombus-free surface area, and cell-free surface area. RESULTS: No significant differences in patency rates were seen between any groups. The thrombus-free surface area was improved for experimental grafts (90%) compared with control grafts (76%), but this improvement did not achieve statistical significance. The cell-free surface area for transduced cells on experimental grafts was 65% compared with 96% for control grafts (p = 0.021) and was comparable with that for nontransduced cells on both control grafts (62%) and experimental grafts (51%; p = 0.201). CONCLUSIONS: Adherence of genetically modified endothelial cells to small-diameter expanded polytetrafluoroethylene grafts in an in vivo physiologic flow model is significantly improved when cells have a more prolonged recovery from G418 selection, when the graft lumen is more uniformly coated with fibronectin before EC seeding, and when seeded grafts are left longer in culture before implantation to develop cell lining stability. The short-term patency rate of these seeded grafts is not affected by increased cell retention; long-term graft patency data and luminal healing require further evaluation.

Animals↗
PubMed1995

Impact debris particles in Jupiter's stratosphere.

The aftermath of the impacts of periodic comet Shoemaker-Levy 9 on Jupiter was studied with the Wide Field Planetary Camera 2 on the Hubble Space Telescope. The impact debris particles may owe their dark brown color to organic material rich in sulfur and nitrogen. The total volume of aerosol 1 day after the last impact is equal to the volume of a sphere of radius 0.5 kilometer. In the optically thick core regions, the particle mean radius is between 0.15 and 0.3 micrometer, and the aerosol is spread over many scale heights, from approximately 1 millibar to 200 millibars of pressure or more. Particle coagulation can account for the evolution of particle radius and total optical depth during the month following the impacts.

Atmosphere↗
PubMed1995

Phase I clinical and pharmacokinetic study of leucovorin and infusional hepatic arterial fluorouracil.

PURPOSE: A phase I and pharmacokinetic trial was performed between October 1993 and June 1994 to determine the maximum-tolerated dose of hepatic arterial infusion (HAI) of fluorouracil (5-FU) and intravenous (IV) leucovorin (folinic acid; FA) in patients with hepatic metastases from colorectal cancer. PATIENTS AND METHODS: Forty-three patients received 310 courses of HAI chemotherapy administered over 48 hours every 2 weeks. The regimen consisted of FA 200 mg/m2 by IV infusion over 2 hours, followed by a loading dose of 5-FU 400 mg/m2 by HAI over 15 minutes, followed by a 22-hour infusion of 5-FU at doses ranging from 0.8 to 1.84 g/m2, with identical chemotherapy on day 2. Pharmacokinetic studies were performed to determine peak and steady-state plasma concentrations (Css) of 5-FU. RESULTS: Severe diarrhea and cardiac and neurologic toxicity were dose-limiting at 1.84 g/m2. The recommended dose for the 22-hour component of the schedule was 1.6 g/m2 and was associated with tolerable toxicity. A Css of 2.2 +/- 0.8 mumol/L for 5-FU was achieved on the recommended schedule, which compares favorably with conventional IV 5-FU regimens. Among 30 patients assessable for response, there were four complete responses and seven partial responses, and 12 patients with stable disease and seven with progressive disease, reported after 3 months (ie, six cycles) of therapy. CONCLUSION: A regimen that combines 5-FU and FA has been identified for regional chemotherapy in patients with hepatic metastases from colorectal cancer. The systemic levels of 5-FU achieved are similar to the conventional IV de Gramont regimen using an identical schedule of 5-FU and FA, which implies that this chemotherapy has the best of both worlds, ie, a regional advantage in delivering high drug concentrations to the target organ with adequate systemic cover for extrahepatic micrometastases.

Adult↗
PubMed1994

Putting an end to ageism.

The National Advisory Council on Aging in 1991 stated a need to encourage students in the health care professions to select careers in gerontology. Indeed, it may be argued that the inclusion of a comprehensive curriculum component on aging in each nursing program is essential to address the demographic changes in Canada. With the increase in longevity it is more important than ever for nursing students to value older persons and not be fearful of interacting with this age group. This raises the question as to what nursing education has done to address this issue.

Aged↗
PubMed1989

Efficacy of exercise for end-stage renal disease patients immediately following high-efficiency hemodialysis: a pilot study.

Nine patients receiving maintenance high-efficiency hemodialysis were studied before and after a 12-week conditioning program to determine the efficacy of exercise immediately following hemodialysis. Each patient performed a combination of bicycle ergometry on the Schwinn Air-Dyne ergometer (SAE) and treadmill walking three times a week for a total exercise time of 15-35 min per session. A low-level Bruce treadmill test and an exercise test on the SAE were administered before and after training. Hematological, serum electrolyte, and serum lipid profiles were also determined before and after training. Following training, there were improvements in exercise capacities for both treadmill walking and ergometry on the SAE. Although a significant increase in serum apolipoprotein A1 was seen following exercise, no significant changes were observed for total cholesterol, low-density-lipoprotein cholesterol, high-density-lipoprotein cholesterol or apolipoprotein B. Additionally, no significant changes were seen in hematological parameters and serum electrolyte profiles following the exercise program. The 9 patients demonstrated an average compliance record of 74%. This study demonstrated that patients on high-efficiency hemodialysis can safely engage in an exercise program immediately following dialysis at intensities and frequencies that can improve their physical work capacities.

Aged↗