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1.
Am J Emerg Med ; 44: 312-314, 2021 06.
Article in English | MEDLINE | ID: mdl-32354528

ABSTRACT

PURPOSE: Acute aortic dissection is a serious and life-threatening condition that requires prompt, effective management. The purpose of this study was to evaluate the efficacy and safety of esmolol for heart rate control in patients with acute aortic dissection in the Emergency Department (ED). METHODS: This was a retrospective, descriptive analysis of patients treated for type A or type B acute aortic dissection in the ED at an academic medical center. The primary outcome was the proportion of patients achieving strict (≤60 bpm) or lenient (≤80 bpm) heart rate control within the first 60 min of therapy at the study site. The primary safety endpoint was the incidence of hypotension, defined as a systolic blood pressure of <90 mmHg or a mean arterial pressure of ≤60 mmHg. RESULTS: Of 266 patients screened, 40 patients met inclusion criteria. Thirty-three patients (82.5%) attained lenient rate control within the first 60 min of esmolol therapy. Eleven patients (27.5%) achieved a strict heart rate goal within the first 60 min of esmolol therapy. Five patients (12.5%) experienced an episode of hypotension during the first 3 h of esmolol therapy. CONCLUSION: In patients treated with esmolol infusion for acute aortic dissection, a lenient HR goal was achieved in most patients. In contrast, esmolol was not associated with attainment of strict HR control in most patients included in this sample. Further studies are warranted to evaluate the exact role of esmolol in acute aortic dissection in a larger patient population.


Subject(s)
Adrenergic beta-1 Receptor Antagonists/therapeutic use , Aortic Aneurysm/therapy , Aortic Dissection/therapy , Heart Rate/drug effects , Propanolamines/therapeutic use , Aged , Emergency Service, Hospital , Female , Humans , Male , Middle Aged , Retrospective Studies
2.
Ir Med J ; 107(8): 240-1, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25282963

ABSTRACT

The diagnosis of Cystic Fibrosis (CF) requires a high clinical suspicion in patients presenting at all ages. Early recognition permits referral to a specialist centre and may reduce the morbidity and mortality associated with CF. We report the case of the oldest patient in Ireland diagnosed with CF at 76 years of age and highlight the clinical features of her presentation.


Subject(s)
Cystic Fibrosis/diagnostic imaging , Cystic Fibrosis/diagnosis , Aged , Female , Humans , Ireland , Radiography, Thoracic
3.
Eur J Cancer Care (Engl) ; 22(1): 79-87, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22738286

ABSTRACT

International and UK data suggest that there are ethnic differences in survival for some malignancies. The aim of the present study was to identify any health inequalities related to lung cancer and ethnicity. Data on 423 patients with a diagnosis of lung cancer treated at a large specialist cancer hospital in London UK were analysed. Data on stage of disease at diagnosis, co-morbidities, socio-economic status, treatments received and survival were collected and examined for differences by ethnic group. There was a significant difference between black and minority ethnic (BME) patients and White-European patients in socio-economic status (Chi-square test P-value < 0.001). BME patients were over-represented in the most deprived socio-economic groups and under-represented in the most affluent. There were no significant differences in histology, stage of disease, co-morbidities and performance status or treatments received between the different ethnic groups. Ethnicity was not associated with survival. Significant prognostic factors for overall survival were performance status (P < 0.001), stage of disease (P = 0.001) and gender (P = 0.003). Our findings suggest that patients from BME groups are over-represented in more deprived socio-economic groups; however, this did not impact on significant prognostic factors or the treatments that they received. Importantly ethnicity did not influence survival.


Subject(s)
Ethnicity/statistics & numerical data , Lung Neoplasms/ethnology , Adult , Age Factors , Aged , Asian People , Black People , Female , Healthcare Disparities , Humans , London/epidemiology , Lung Neoplasms/mortality , Male , Middle Aged , Prognosis , Sex Factors , Smoking/adverse effects , Socioeconomic Factors , Survival Analysis , White People
4.
Clin Oncol (R Coll Radiol) ; 35(2): e163-e172, 2023 02.
Article in English | MEDLINE | ID: mdl-36402621

ABSTRACT

AIMS: The standard evaluation of older lung cancer or mesothelioma patients for systemic anti-cancer treatment, based on performance status, is inaccurate. We used the G8 questionnaire to assess a patient's fitness for chemotherapy and explored the correlations between G8 scores, treatment decisions and clinical outcomes. MATERIALS AND METHODS: In total, 201 older patients (≥70 years) with advanced lung cancer or mesothelioma were prospectively assessed by standard clinical methods and a G8 questionnaire. Treatment decisions before and after reviewing the G8 score were documented. Patients were divided into low (<11), intermediate (11-14) and high (>14) G8 score groups. Patients' characteristics, treatment plans and clinical outcomes among each G8 score group were compared. Similar analyses were compared between good (<2) and poor (≥2) performance status. RESULTS: 10.1% of patients' treatment plans changed after oncologists reviewed G8 scores. The G8 score correlated inversely with performance status. More patients with low G8 scores (22.5%) were offered the best supportive care compared with 4.5% in intermediate and 1.9% in high G8 score groups. More patients (30.1%) with low G8 scores had treatment changed from chemotherapy to best supportive care on the planned day of their treatment, compared with intermediate (7.5%) and high (6.1%) G8 score groups. High G8 score patients received higher chemotherapy intensity and survived longer than patients with intermediate or low G8 scores. CONCLUSIONS: The G8 score with two cut-off values can predict functional status, chemotherapy tolerability and prognosis in older patients with lung cancer or mesothelioma, thus supporting oncologists on treatment decisions for this population.


Subject(s)
Lung Neoplasms , Mesothelioma , Humans , Aged , Geriatric Assessment/methods , Lung Neoplasms/drug therapy , Prognosis , Mesothelioma/drug therapy , Surveys and Questionnaires
5.
Ir Med J ; 105(8): 275-7, 2012 Sep.
Article in English | MEDLINE | ID: mdl-23155916

ABSTRACT

There has been an increase in the number of pulmonary infections caused by non-tuberculous mycobacteria (NTM) in the non HIV-infected population with a heightened awareness clinically and in the laboratory of the significance of these respiratory isolates and newer identification techniques. As far as we are aware, this is the first case report of pulmonary Mycobacteium szulgai infection in Ireland.


Subject(s)
Mycobacterium Infections, Nontuberculous/diagnosis , Nontuberculous Mycobacteria , Tuberculosis, Pulmonary/diagnosis , Humans , Male , Middle Aged , Mycobacterium Infections, Nontuberculous/drug therapy , Tomography, X-Ray Computed , Tuberculosis, Pulmonary/drug therapy
6.
Br J Cancer ; 102(4): 629-38, 2010 Feb 16.
Article in English | MEDLINE | ID: mdl-20104223

ABSTRACT

Small cell lung cancer (SCLC) is a significant health problem worldwide because of its high propensity for relapse. This review discusses existing and future therapies for the treatment of SCLC.


Subject(s)
Lung Neoplasms/therapy , Small Cell Lung Carcinoma/therapy , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/therapeutic use , Antineoplastic Protocols , Biomedical Research/trends , Choice Behavior , Humans , Lung Neoplasms/diagnosis , Lung Neoplasms/pathology , Neoplasm Staging/methods , Prognosis , Small Cell Lung Carcinoma/diagnosis , Small Cell Lung Carcinoma/pathology
7.
Eur J Cancer ; 44(2): 224-7, 2008 Jan.
Article in English | MEDLINE | ID: mdl-17928219

ABSTRACT

Immunotherapy with a heat-killed suspension of Mycobacterium vaccae (SRL172), given with chemotherapy, in a phase III trial against non-small-cell-lung cancer showed no improvement in the primary endpoint of survival over chemotherapy alone in the initial published analysis. Compliance was poor, with on average only 53% of patients receiving more than 2 injections in the SRL172 arm of the study. Quality of life was, however, improved in those receiving SRL172. Secondary analyses based on compliance with therapy showed that immunotherapy led to significantly improved survival times of patients with adenocarcinoma but, by contrast, had no beneficial effect on survival times of patients with squamous cell carcinoma. Survival of adenocarcinoma patients receiving SRL172 was increased by a mean of 135 days (p=0.0009, Kaplan-Meier log rank test) and survival after 4 or 5 doses of SRL172 showed a difference of greater than 100 days (p<0.05, Mantel-Hänszel log rank test) in the group receiving SRL172 in addition to chemotherapy. Despite the problems inherent in a secondary analysis, these results encourage further research on the role of killed preparations of adjuvant-rich micro-organisms, including saprophytic mycobacteria such as M. vaccae, and members of related genera in the therapy of a range of cancers.


Subject(s)
Adenocarcinoma/therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bacterial Vaccines/therapeutic use , Immunotherapy/methods , Lung Neoplasms/therapy , Bacterial Vaccines/administration & dosage , Carcinoma, Non-Small-Cell Lung/therapy , Carcinoma, Squamous Cell/therapy , Disease-Free Survival , Female , Humans , Male , Middle Aged , Patient Compliance , Quality of Life , Treatment Outcome
8.
Clin Oncol (R Coll Radiol) ; 20(2): 142-7, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18093813

ABSTRACT

AIMS: Palliative chemotherapy in non-small cell lung cancer (NSCLC) has been established since 1995 and little chemotherapy treatment was given to these patients before 1990. This retrospective study investigates the treatment outcome of elderly patients (age>or=70 years) with NSCLC over the past 13 years in a large UK cancer centre. MATERIALS AND METHODS: A comparison of all-cause survival between the time periods 1990-1994, 1995-1999 and 2000-2004 was adjusted for age, gender, stage and performance status. A comparison of survival was also made between three age groups: 70-74, 75-79 and 80+ years. RESULTS: Between 1990 and 2004, 302 patients>or=70 years had NSCLC. There were differences in age and performance status between the time periods. There was no improvement in median survival between the three time periods (P=0.6). There was little difference in outcome between the three age cohorts. CONCLUSIONS: The analysis shows that there has been no significant improvement in survival for elderly patients with advanced lung cancer treated with chemotherapy in the past 13 years.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Aged , Aged, 80 and over , Female , Humans , Male , Retrospective Studies , Survival Analysis , Time Factors , Treatment Outcome
9.
Ir J Med Sci ; 187(2): 429-434, 2018 May.
Article in English | MEDLINE | ID: mdl-28812224

ABSTRACT

BACKGROUND: Candidaemia is an important nosocomial infection, seen frequently in immunocompromised and critically ill patients and increasingly recognised in cystic fibrosis (CF) patients with totally implantable venous access devices (TIVADs). This study aims to investigate the incidence and risk factors for the development of TIVAD-associated candidaemia and to assess the rate of TIVAD-related complications in CF patients. METHODS: A 10-year retrospective study was carried out on adult CF patients attending a single centre. Complications were recorded including the incidence of candidaemia and correlated to clinical parameters. Complication rates were calculated based on incidence per 1000 catheter days. Statistical analysis was performed using Mann-Whitney U test and Fisher's exact test. RESULTS: Fourteen cases of candidaemia were observed in the CF cohort, primarily caused by Candida parapsilosis and Candida albicans. Candidaemia was associated with lower FEV1 (p = 0.0117) and higher frequency of pulmonary exacerbation (p < 0.0001). A TIVAD complication rate of 0.337/1000 catheter days was observed in the CF cohort. Complications included venous thrombosis, stenosis, and port extrusion; complications were independently associated with more frequent pulmonary exacerbations (p = 0.04). CONCLUSIONS: TIVAD complications are observed more commonly in those with lower FEV1 and frequent pulmonary exacerbations, suggesting that candidaemia may be related to antibiotic use and furthermore can occur following invasive procedures causing translocation of fungal species allowing transformation from colonisation to pathogenic infection.


Subject(s)
Candida/pathogenicity , Cystic Fibrosis/complications , Prostheses and Implants/adverse effects , Adult , Cystic Fibrosis/therapy , Female , Humans , Incidence , Male , Retrospective Studies , Risk Factors
10.
J Clin Invest ; 91(4): 1761-8, 1993 Apr.
Article in English | MEDLINE | ID: mdl-8473516

ABSTRACT

A subclinical vitamin K deficiency was induced in 32 healthy subjects (four groups of eight males and females) aged 20-40 and 60-80 yr residing in the Metabolic Research Unit of the Human Nutrition Research Center on Aging at Tufts University. Volunteers were initially fed (4 d) a baseline-period diet containing the recommended daily allowance for vitamin K which is equivalent to 80 micrograms/d of phylloquinone (vitamin K1). During the baseline period various parameters of vitamin K nutritional status were monitored. The baseline period was followed by a 13-d depletion period during which the subjects were fed a very low vitamin K1 diet (approximately 10 micrograms/d). After depletion, the subjects entered a 16-d repletion period (four stages lasting 4 d each) during which time they were repleted with 5, 15, 25, and 45 micrograms of vitamin K1 per day. Vitamin K1 depletion dramatically and significantly decreased plasma vitamin K1 levels (P < 0.0001) in both elderly and young groups to values 13-18% of day 1 (elderly 0.22 nM, young 0.14 nM). Repleting the subjects with up to 45 micrograms of vitamin K1 per day failed, in the case of the young subjects, to bring plasma vitamin K1 levels back into the normal range. Dietary vitamin K1 restriction induced different responses in the urinary excretion of gamma-carboxyglutamic acid between the young and the elderly subjects with values decreasing significantly (P < 0.03) in the young while remaining unchanged in the elderly. The vitamin K1 depletion period had no significant effect on either prothrombin and activated partial thromboplastin times, or Factor VII and protein C (as determined by antigenic and functional assays). By using a monoclonal antibody, decarboxy prothrombin was found to increase slightly but significantly in both groups (P < 0.05) as a consequence of the low vitamin K1 diet. This study clearly shows that a diet low in vitamin K1 can result in a functional subclinical deficiency of vitamin K (decreased urinary gamma-carboxyglutamic acid excretion) without affecting blood coagulation.


Subject(s)
Vitamin K Deficiency/chemically induced , Vitamin K/administration & dosage , 1-Carboxyglutamic Acid/biosynthesis , 1-Carboxyglutamic Acid/urine , Adult , Aged , Aged, 80 and over , Aging/physiology , Antigens/analysis , Diet , Factor VII/immunology , Factor VII/physiology , Female , Humans , Male , Middle Aged , Nutritional Status , Partial Thromboplastin Time , Protein C/immunology , Protein C/physiology , Prothrombin Time , Vitamin K/blood , Vitamin K/metabolism
11.
Eur J Cancer ; 61: 102-10, 2016 07.
Article in English | MEDLINE | ID: mdl-27156228

ABSTRACT

BACKGROUND: Dyspnoea is one of the commonest symptoms of lung cancer. Opioids can reduce dyspnoea. This study investigates acupuncture for relief of breathlessness in lung cancer. METHODS: We performed a single-centre, randomised phase II study of 173 patients with non-small cell lung cancer or mesothelioma with dyspnoea score of ≥4 on visual analogue scale (VAS). Randomisation was to acupuncture alone (A), morphine alone (M) or both (AM). Acupuncture was administered at upper sternal, thoracic paravertebral, trapezius trigger points and LI4. Manubrial semi-permanent acupuncture studs were inserted and massaged when symptomatic. Arm A patients received rescue morphine. Primary end-point was proportion of patients achieving ≥1.5 improvement in VAS dyspnoea at 4 h. Measurements continued to day 14 and included VAS relaxation, line analogue rating (Lar) anxiety, hospital anxiety and depression and European Organisation for Research and Treatment of Cancer quality-of-life scores. RESULTS: Dyspnoea VAS improved ≥1.5 in 74%, 60% and 66% of arms A, M and AM, respectively, and was maintained in 45% at 2 weeks. There was no statistically significant difference between arms. VAS relaxation improved in arms A (1.06 points) and AM (1.48 points) compared to arm M (-0.19 points, p<0.001). At 7 d, the Lar anxiety score improved in arm A (1.5 points), arm AM (1.2 points) and arm M (no change, p=0.003). Fewer patients received at least one morphine dose in arm A compared with arm M or AM (21% versus 87% versus 87%, respectively, p<0.001). CONCLUSIONS: A, M and AM were effective in relieving dyspnoea. Acupuncture relieved anxiety and was morphine sparing, providing an alternative to morphine.


Subject(s)
Acupuncture Therapy , Analgesics, Opioid/therapeutic use , Carcinoma, Non-Small-Cell Lung/complications , Dyspnea/therapy , Lung Neoplasms/complications , Mesothelioma/complications , Morphine/therapeutic use , Adult , Aged , Aged, 80 and over , Combined Modality Therapy , Female , Humans , Male , Middle Aged
12.
Eur J Cancer ; 59: 65-78, 2016 05.
Article in English | MEDLINE | ID: mdl-27016624

ABSTRACT

Therapeutic options in locally advanced non-small cell lung cancer (NSCLC) have expanded in the past decade to include a palate of targeted interventions such as high dose targeted thermal ablations, radiotherapy and growing platform of antibody and small molecule therapies and immunotherapies. Although these therapies have varied mechanisms of action, they often induce changes in tumour architecture and microenvironment such that response is not always accompanied by early reduction in tumour mass, and evaluation by criteria other than size is needed to report more effectively on response. Functional imaging techniques, which probe the tumour and its microenvironment through novel positron emission tomography and magnetic resonance imaging techniques, offer more detailed insights into and quantitation of tumour response than is available on anatomical imaging alone. Use of these biomarkers, or other rational combinations as readouts of pathological response in NSCLC have potential to provide more accurate predictors of treatment outcomes. In this article, the robustness of the more commonly available positron emission tomography and magnetic resonance imaging biomarker indices is examined and the evidence for their application in NSCLC is reviewed.


Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma, Non-Small-Cell Lung/therapy , Lung Neoplasms/therapy , Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/blood supply , Catheter Ablation/methods , Cell Hypoxia , Cell Proliferation , Forecasting , Humans , Immunotherapy/methods , Lung Neoplasms/blood supply , Magnetic Resonance Imaging , Molecular Targeted Therapy/methods , Multimodal Imaging , Observer Variation , Positron Emission Tomography Computed Tomography , Positron-Emission Tomography , Radiopharmaceuticals , Treatment Outcome , Tumor Microenvironment
13.
Biochim Biophys Acta ; 957(2): 243-53, 1988 Nov 23.
Article in English | MEDLINE | ID: mdl-3191142

ABSTRACT

The compound p-mercuribenzenefulfonate was found to affect the self-association behavior of both spectrin and actin. The reagent brings about the depolymerization of F-actin, as judged from the decrease in the fluorescence of an attached pyrene label, with a second-order rate constant an order of magnitude less than that for the disruption of isolated erythrocyte cytoskeletons. Therefore, it is unlikely that the depolymerization of actin is the rate-determining step in the mercurial-dependent disruption of the erythrocyte cytoskeleton. Low reagent concentrations caused an initial rapid dissociation of spectrin tetramers at a rate comparable with that of cytoskeleton disruption. Prolonged incubation, or higher reagent concentrations, resulted in subsequent aggregation of spectrin. The reagent also prevented the interaction between spectrin and actin, presumably through its depolymerization of actin and its effects on spectrin. The early event in the disruption of isolated erythrocyte cytoskeletons by p-mercuribenzenesulfonate thus appears to be the dissociation of spectrin oligomers. Subsequent depolymerization of actin brought about by the reagent then results in total disruption of the cytoskeleton.


Subject(s)
Actins , Erythrocyte Membrane/drug effects , Mercuribenzoates/pharmacology , Spectrin/drug effects , Actins/blood , Electrophoresis, Polyacrylamide Gel , Erythrocyte Membrane/ultrastructure , Ethylmaleimide/pharmacology , Humans , In Vitro Techniques , Macromolecular Substances , Polymers , Protein Binding/drug effects
14.
J Clin Oncol ; 11(11): 2112-7, 1993 Nov.
Article in English | MEDLINE | ID: mdl-8229125

ABSTRACT

PURPOSE: We performed a phase II study of single-agent carboplatin against metastatic/locally advanced breast cancer using a pharmacokinetically guided dose schedule, to define further the potential role for this agent in combination and high-dose therapy. PATIENTS AND METHODS: Forty patients with metastatic/locally advanced breast cancer were treated with carboplatin based on glomerular filtration rate (GFR) to achieve an area under the concentration-versus-time curve (AUC) of 7 mg/mL.min, with each course repeated at 4-week intervals. The median age was 57 years (range, 37 to 71). RESULTS: Ten patients achieved a partial response (PR), for an overall response rate of 25% (95% confidence interval, 13% to 41%). One of 13 (8%) previously treated patients responded compared with nine of 27 (33%) patients who had not received previous chemotherapy. Median response duration was 18 weeks (range, 10 to 68). World Health Organization (WHO) grade 2 or greater toxicity was as follows: anemia, 42%; leukopenia, 20%; thrombocytopenia, 35%; nausea/vomiting, 39%; and infection, 9%. CONCLUSION: This study confirms other reports indicating that carboplatin has moderate activity in previously untreated patients, but not in previously treated patients. In our view, carboplatin is a more appropriate agent than cisplatin for inclusion in high-dose chemotherapy schedules with autologous bone marrow rescue, and our results support the concept of calculating dose escalation on the basis of the area under the dose-response curve using the Calvert formula, rather than on surface area.


Subject(s)
Breast Neoplasms/drug therapy , Carboplatin/therapeutic use , Adult , Aged , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Carboplatin/administration & dosage , Carboplatin/adverse effects , Carboplatin/pharmacokinetics , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Glomerular Filtration Rate/drug effects , Humans , Middle Aged , Treatment Outcome
15.
J Clin Oncol ; 18(12): 2378-84, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10856097

ABSTRACT

PURPOSE: Eniluracil (776C85) is an effective inactivator of dihydropyrimidine dehydrogenase that allows continuous low-dose oral fluorouracil (5-FU) to be given with predicable oral bioavailability. We have assessed this as first-line oral chemotherapy for patients with advanced/metastatic breast cancer. PATIENTS AND METHODS: Patients with histologically proven, locally advanced or metastatic breast cancer without previous chemotherapy for advanced disease were entered onto this open-label phase II study. Patients received oral 5-FU 1.0 mg/m(2) with eniluracil 10 mg/m(2), both given twice daily for the first 28 days of each 35-day cycle, continuing until disease progression or unmanageable toxicity. RESULTS: Thirty-three patients were entered, with a median age of 53 years. Sixteen partial responses were seen in twenty-nine assessable patients (55%; 95% confidence interval, 37% to 73%), including responses in four (40%) out of 10 patients who had received prior adjuvant 5-FU. Seven patients had stable disease for at least 3 months with symptom improvement. Median response duration was 14 months (range, 10 to 18+ months). Toxicity was low. There were only two episodes of drug-related grade 3 nonhematologic toxicity (diarrhea and infection), and only 6%, 3%, and 3% of patients developed granulocytopenia, thrombocytopenia, and neutropenic sepsis, respectively. Mild (grade 1/2) diarrhea occurred in 39% of patients, hand-foot syndrome in 15%, nausea in 27%, and mucositis in 18%. Toxicity-associated delay and dose reduction occurred in only 2% and 5% of courses, respectively. CONCLUSION: First-line treatment with the combination of oral 5-FU and eniluracil has high activity in patients with advanced breast cancer comparable with the most active conventional cytotoxic agents but with strikingly less toxicity.


Subject(s)
Antimetabolites, Antineoplastic/administration & dosage , Breast Neoplasms/drug therapy , Enzyme Inhibitors/administration & dosage , Fluorouracil/administration & dosage , Uracil/analogs & derivatives , Administration, Oral , Adult , Aged , Aged, 80 and over , Antimetabolites, Antineoplastic/adverse effects , Antimetabolites, Antineoplastic/pharmacokinetics , Biological Availability , Breast Neoplasms/pathology , Drug Administration Schedule , Enzyme Inhibitors/pharmacology , Female , Fluorouracil/adverse effects , Fluorouracil/pharmacokinetics , Humans , Middle Aged , Treatment Outcome , Uracil/administration & dosage , Uracil/pharmacology
16.
J Clin Oncol ; 12(6): 1259-65, 1994 Jun.
Article in English | MEDLINE | ID: mdl-8201387

ABSTRACT

PURPOSE: To investigate the efficacy and toxicity of continuous infusion fluorouracil (5-FU) with every-3-weeks epirubicin and cisplatin (ECF) in advanced breast cancer in a phase II study. PATIENTS AND METHODS: Forty-three patients with metastatic (n = 29) or locally advanced/inflammatory (n = 14) breast cancer were treated with 5-FU 200 mg/m2/d via a Hickman line using an ambulatory pump for 6 months with epirubicin 50 mg/m2 intravenously (IV) and cisplatin 60 mg/m2 IV every 3 weeks, for eight courses. RESULTS: The overall response rate (complete plus partial) was 84% (95% confidence interval [Cl], 76% to 96%), with a complete response rate of 24% (95% Cl, 9% to 40%) in patients with metastatic disease and 36% (95% Cl, 11% to 61%) in patients with locally advanced disease. The main World Health Organization [WHO] grade 3 or 4 toxicities included leukopenia, emesis, and alopecia. CONCLUSION: Infusional ECF is a highly active regimen in advanced breast cancer and warrants evaluation in high-risk early breast cancer.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Cisplatin/administration & dosage , Cisplatin/adverse effects , Epirubicin/administration & dosage , Epirubicin/adverse effects , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , Infusions, Intravenous , Middle Aged , Neoplasm Metastasis
17.
J Clin Oncol ; 19(5): 1336-43, 2001 Mar 01.
Article in English | MEDLINE | ID: mdl-11230476

ABSTRACT

PURPOSE: So far there are no published data on optimal duration of chemotherapy for advanced non-small-cell lung cancer (NSCLC); six or more courses are usually recommended. We have carried out a multicenter randomized trial comparing three versus six courses of chemotherapy. PATIENTS AND METHODS: Patients with stage IIIb or IV NSCLC were randomized at start of treatment to receive either three or six courses of mitomycin 8 mg/m(2) (courses 1, 2, 4, and 6), vinblastine 6 mg/m(2), and cisplatin 50 mg/m(2) (MVP) every 21 days. Treatment was stopped early in both arms for progressive disease or unacceptable toxicity. Key end points were overall survival, duration of symptom relief, and quality-of-life assessment using the European Organization for Research and Treatment of Cancer (EORTC) core questionnaire QLQ-C30 with lung cancer-specific module QLQ-LC13. RESULTS: Three hundred eight patients were randomized. Seventy-two percent of the 155 patients randomized to three courses completed treatment. In the 153 patients randomized to six courses, 73% completed three courses and 31% six courses. Median survival was 6 versus 7 months, respectively, and 1-year survival 22% versus 25% (P =.2). Median duration of symptom relief was 4.5 months (both arms), and 8% versus 18% had continuing symptom relief (P =.4). Quality-of-life parameters were the same or improved for patients randomized to only three courses, including significantly decreased fatigue (P =.03) and a trend toward decreased nausea and vomiting (P =.06). CONCLUSION: Our findings show no evidence for additional clinical benefit by continuing MVP chemotherapy beyond three courses. This challenges current orthodoxy of six courses or more. Further trials addressing duration of chemotherapy are now warranted, particularly with newer chemotherapy schedules.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carcinoma, Non-Small-Cell Lung/pathology , Cisplatin/administration & dosage , Disease Progression , Drug Administration Schedule , Female , Humans , Lung Neoplasms/pathology , Male , Middle Aged , Mitomycin/administration & dosage , Quality of Life , Survival Analysis , Vinblastine/administration & dosage
18.
J Clin Oncol ; 13(3): 547-52, 1995 Mar.
Article in English | MEDLINE | ID: mdl-7884414

ABSTRACT

PURPOSE: To evaluate in a randomized clinical trial systemic chemoendocrine therapy used as primary (neo-adjuvant) treatment before surgery in women with primary operable breast cancer. PATIENTS AND METHODS: Patients aged less than 70 years with clinically palpable, primary operable breast cancer diagnostically confirmed by fine-needle aspiration cytology (FNAC) and suitable for treatment with surgery, radiotherapy, cytotoxic chemotherapy, and tamoxifen were considered eligible. Patients randomized to neoadjuvant treatment received four cycles of chemo-therapy for 3 months before surgery followed by another four cycles after surgery, and were compared with patients randomized to adjuvant therapy who received eight cycles of chemotherapy over 6 months after surgery. RESULTS: Of 212 patients who were randomized to receive either adjuvant (n = 107) or neoadjuvant (n = 105) chemoendocrine therapy, 200 are now assessable for response. The two groups are comparable for age, menopausal status, disease stage, and surgical requirements. The overall clinical response rate was 85%, with a complete histologic response rate of 10%. There was a significant reduction in the requirement for mastectomy in patients who received neoadjuvant treatment (13%) as compared with those who received adjuvant therapy (28%) (P < .005). Symptomatic and hematologic acute toxicity was low and similar for adjuvant and neoadjuvant therapy. The median follow-up period for patients in this trial is 28 months, during which time four patients have relapsed locally and 20, including one of the local relapses, have developed metastatic disease, 19 of whom have died. The follow-up period is too brief to evaluate relapse rate or survival duration. CONCLUSION: This trial confirms previous reports of a high rate of response to neoadjuvant therapy, but is the first to include small primary cancers and to show, in the context of a randomized trial, a reduction in the requirement for mastectomy. Until disease-free and overall survival data are available from the larger National Surgical Adjuvant Breast and Bowel Project (NSABP)-18 trial, such neoadjuvant treatment cannot be recommended outside of a clinical trial.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Tamoxifen/therapeutic use , Adult , Aged , Breast Neoplasms/mortality , Breast Neoplasms/surgery , Chemotherapy, Adjuvant , Combined Modality Therapy , Disease-Free Survival , Female , Follow-Up Studies , Humans , Mastectomy , Methotrexate/administration & dosage , Middle Aged , Mitomycins/administration & dosage , Mitoxantrone/administration & dosage , Pilot Projects , Remission Induction , Survival Rate
19.
Am J Clin Nutr ; 65(3): 779-84, 1997 Mar.
Article in English | MEDLINE | ID: mdl-9062529

ABSTRACT

The response of osteocalcin and other biochemical markers of vitamin K status to diets formulated to contain different amounts of phylloquinone was assessed in nine healthy subjects aged 20-33 y. Subjects resided in a metabolic ward for two 15-d cycles with a minimum of 6 wk between cycles. A mixed diet containing 100 micrograms phylloquinone/d was fed throughout both cycles; however, the phylloquinone content of one of the cycles was increased to a total of 420 micrograms/d on days 6 through 10 by fortifying corn oil in the diet with phylloquinone (supplemented diet). Total serum osteocalcin concentrations were not affected by either of the dietary treatments. The percentage of undercarboxylated osteocalcin increased an average of 28% over the 15-d cycle with the mixed diet (P < 0.05) and declined significantly an average of 41% with 5 d of the supplemented diet (day 6: 21.9 +/- 1.3%, day 11: 12.8 +/- 1.1%; P = 0.0001) with a rise after the return to the mixed diet (16.7 +/- 1.3%, P < 0.001). Plasma phylloquinone concentrations increased significantly with supplementation (day 6: 0.95 +/- 0.16 nmol/L, day 11: 1.40 +/- 0.29 nmol/L; P < 0.001) and then rapidly returned to presupplementation concentrations on returning to the mixed diet. Twenty-four-hour ratios of urinary gamma-carboxyglutamic acid to creatinine were unchanged with the supplemented diet; however, excretion declined to 91 +/- 2% of baseline after 10 d on the mixed diet (P = 0.01). These results show that undercarboxylated osteocalcin, plasma phylloquinone, and urinary gamma-carboxyglutamic acid excretion appear to be sensitive measures of vitamin K nutritional status because all of these variables were responsive to changes in dietary intake.


Subject(s)
1-Carboxyglutamic Acid/urine , Antifibrinolytic Agents/administration & dosage , Antifibrinolytic Agents/blood , Diet , Osteocalcin/blood , Vitamin K 1/administration & dosage , Vitamin K 1/blood , Vitamin K/physiology , Adult , Female , Humans , Male , Nutritional Status , Prothrombin Time
20.
Am J Clin Nutr ; 67(6): 1226-31, 1998 Jun.
Article in English | MEDLINE | ID: mdl-9625097

ABSTRACT

The purpose of this study was to characterize the absorption and transport of phylloquinone (vitamin K1) by plasma lipoproteins. Twenty-six healthy subjects (11 men and 15 women) aged 20-78 y received phylloquinone in the amount of either 1.43 or 50 microg/kg body wt orally with a fat-rich meal containing 1.0 g/kg body wt of fat, carbohydrate, and protein and 7.0 mg cholesterol/kg body wt. Blood was obtained at baseline (0 h) and 3, 6, 9, and 12 h after the meal for the measurement of plasma lipid and phylloquinone concentrations in plasma and lipoprotein subfractions. In both groups of subjects, triacylglycerol concentrations peaked after 3 h in plasma and in the triacylglycerol-rich lipoprotein fraction, composed of chylomicrons and VLDLs. Plasma phylloquinone concentrations peaked at 6 h. At baseline and during the postprandial phase, > 53% of plasma phylloquinone was carried by the triacylglycerol-rich lipoprotein fraction. In 9 of the 11 subjects supplemented with 50 microg phylloquinone/kg, plasma lipoproteins were isolated by sequential ultracentrifugation. In these subjects the fraction of plasma phylloquinone carried by LDLs and by HDLs increased progressively from 3% and 4% at 3 h to 14% and 11% at 12 h, respectively. Our data indicate that whereas triacylglycerol-rich lipoproteins are the major carriers of phylloquinone, LDL and HDL may carry small fractions of this vitamin.


Subject(s)
Antifibrinolytic Agents/blood , Antifibrinolytic Agents/pharmacokinetics , Dietary Fats/metabolism , Lipoproteins/blood , Vitamin K 1/pharmacokinetics , Administration, Oral , Adult , Aged , Antifibrinolytic Agents/administration & dosage , Biological Transport , Cholesterol/blood , Dietary Fats/administration & dosage , Female , Humans , Intestinal Absorption , Lipoproteins/administration & dosage , Lipoproteins/physiology , Male , Middle Aged , Triglycerides/blood , Vitamin K 1/administration & dosage , Vitamin K 1/blood
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