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Biomedical subjects

Karen Kelly

Publications and source records attributed to Karen Kelly.

At least 37 records · Page 2Linked to original sources
PubMed2005

Therapeutic strategies for combined-modality therapy of locally advanced non-small-cell lung cancer: rationale for consolidation docetaxel therapy.

Currently, there is no accepted standard of care for locally advanced and surgically unresectable non-small-cell lung cancer. Typically, treatment for patients with good performance status consists of a combination of chemotherapy and thoracic radiation therapy (RT), but the integration of these modalities and the respective dose schedules vary considerably. Herein, we review the rationale for a treatment paradigm employing consolidation docetaxel therapy after concurrent chemotherapy/RT and the results of recent clinical trials using this approach.

Antineoplastic Agents, Phytogenic↗
PubMed2005

If all ambulances could fly: putting provincial standards of emergency care access to the test in Northern British Columbia.

INTRODUCTION: Geographic access to emergency treatment remains an important public policy concern as rural emergency medical systems respond to various pressures to centralize services. Geographical Information Systems (GIS) are effective tools to determine what proportion of a given population is adequately served by existing or proposed service distributions. METHODS: This study compares 2 GIS approaches to determining whether recent standards of emergency care access established by the British Columbia Ministry of Health Services are being met in Northern British Columbia. In particular, we compare results obtained using the more commonly used straight-line, or "as the crow flies," method with those obtained using a more sophisticated method that estimates travel time using digitally referenced road network data. RESULTS: Both methods reveal that provincial standards of emergency access are not being met in Northern British Columbia. CONCLUSION: In terms of comparing the 2 approaches, the network technique indicated a lower level of access and was more accurate in identifying populations residing inside and outside the "golden hour" of emergency care.

Air Ambulances↗
PubMed2004

A phase I and pharmacokinetic study of exisulind and docetaxel in patients with advanced solid tumors.

PURPOSE: Exisulind (sulindac sulfone, FGN-1, Aptosyn) is a sulindac metabolite that induces apoptosis via inhibition of cyclic GMP-phosphodiesterase. This agent demonstrated tumor growth inhibition in rodent models of colon, breast, prostate, and lung carcinogenesis. In an orthotopic model of human non-small-cell lung cancer, the combination of exisulind and docetaxel prolonged survival in athymic nude rats, forming the basis of this phase I combination study. EXPERIMENTAL DESIGN: This study evaluated the toxicity and pharmacokinetics of combining exisulind (150-250 mg) given orally twice daily and docetaxel (30-36 mg/m2) administered intravenously on days 1, 8, and 15 of a 4-week cycle. RESULTS: Twenty patients with a range of advanced solid tumors (median age, 59 years; age range, 35-77 years; median performance status, 1) received a total of 70 courses. Observed adverse events were mild to moderate, and there was no dose-limiting toxicity at any level. Grade 3 gastrointestinal toxicities were present in 10 of the 70 cycles (10%) and included nausea, vomiting, dyspepsia, and elevated alkaline phosphatase. Neutropenia was present in four cycles in patients treated with a docetaxel dose of 36 mg/m2. Pharmacokinetic analysis did not demonstrate a clear effect of exisulind on docetaxel pharmacokinetics and vice versa. Relationships were evident between the plasma concentration of exisulind and the development of grade 2 or greater toxicities. One third of patients maintained stable disease for 3 to 12 cycles, but no objective responses were observed. CONCLUSIONS: The combination of docetaxel (36 mg/m2, weekly) and exisulind (500 mg/d) was reasonably well tolerated, and it is undergoing phase II testing in patients with non-small-cell lung cancer.

Adult↗
PubMed2004

Phase II study of pemetrexed-gemcitabine combination in patients with advanced-stage non-small cell lung cancer.

PURPOSE: Cisplatin is one of the most active agents for the treatment of non-small cell lung cancer (NSCLC). It is also known for significant toxicity, which makes it unsuitable for certain patients. Our purpose was to evaluate the efficacy and toxicity of a promising cisplatin-free combination, gemcitabine plus pemetrexed, in NSCLC. EXPERIMENTAL DESIGN: Chemo-naive patients with inoperable NSCLC were eligible for this study. Gemcitabine (1250 mg/m2) was given intravenously on days 1 and 8, followed by intravenous pemetrexed (500 mg/m2) on day 8. After inclusion of 13 patients, folic acid and vitamin B12 supplementation was added to lower pemetrexed-induced toxicity. Quality of life was assessed with the Lung Cancer Symptom Scale. RESULTS: Sixty patients enrolled; 58 were evaluable for response. All patients had a World Health Organization performance status of 0 or 1. Eighty-seven percent had stage IV disease. Nine patients had a confirmed partial response [overall response rate, 15.5%; 95% confidence interval (CI), 7.3-27.4%]. Twenty-nine (50.0%) patients had stable disease. Median overall survival was 10.1 months (95% CI, 7.9-13.0 months), with a 1- and 2-year overall survival of 42.6% (95% CI, 30.0-55.3%) and 18.5% (95% CI, 7.9-29.1%). Median progression-free survival was 5.0 months. Median response duration was 3.3 months. There were no deaths attributed to treatment. Common Toxicity Criteria grade 3/4 toxicities were neutropenia (61.7%), febrile neutropenia (16.7%), fatigue (23.3%), and elevations of aspartate aminotransferase (15.0%) and alanine aminotransferase (20.0%). CONCLUSIONS: This combination had good tolerance and achieved promising overall survival with extended 1- and 2-year survival rates. This cisplatin-free regimen warrants further evaluation in randomized trials.

Adult↗
PubMed2004

Randomized phase II trial of sequential chemotherapy in advanced non-small cell lung cancer (SWOG 9806): carboplatin/gemcitabine followed by paclitaxel or cisplatin/vinorelbine followed by docetaxel.

PURPOSE: Improving chemotherapeutic efficacy in non-small cell lung cancer (NSCLC) will require the development of new drugs or new strategies to better use currently available agents. Sequential administration offers an opportunity to increase drug diversity while maintaining dose intensity. On the basis of the data indicating the activity of taxanes as second-line therapy and the lack of efficacy for more than three cycles of platinum-based therapy, this randomized Phase II study tested the concept of planned sequential chemotherapy in advanced NSCLC. EXPERIMENTAL DESIGN: Patients with selected stage IIIb (pleural effusion)/stage IV NSCLC, performance status of 0-1 and normal organ function were eligible. THERAPY: arm 1, carboplatin (area under the curve = 5.5 mg/ml x min day 1) and gemcitabine (1000 mg/m(2) days 1 and 8 every 21 days x 3) followed by paclitaxel (225 mg/m(2) every 21 days x 3) or arm 2, cisplatin (100 mg/m(2) day 1), vinorelbine (25 mg/m(2) days 1 and 8 every 21 d x 3) followed by docetaxel (75-100 mg/m(2) every 21 days x 3). RESULTS: Two-hundred four patients were accrued, of whom, 178 were eligible and evaluable. Eighty percent of patients were stage IV on arm 1 and 85% on arm 2. Response rates were 21 and 28% on arms 1 and 2, respectively. Median, 1-year and 2-year survivals were 9 months, 34 and 13%, and 9 months, 36 and 8%, on arms 1 and 2, respectively. CONCLUSIONS: Sequential therapy, as used in this study, resulted in comparable efficacy to previous Southwest Oncology Group trials of two drug combinations in this population; however, it failed to meet criteria for further study.

Adenocarcinoma↗
PubMed2004

A preliminary open study of the tolerability and effectiveness of nefazodone in major depressive disorder: comparing patients who recently discontinued an SSRI with those on no recent antidepressant treatment.

Anecdotal evidence suggests that the recent discontinuation of an SSRI may confound the tolerability of the initiation of nefazodone treatment. We sought to determine whether recent discontinuation of an SSRI interferes with effectiveness and/or tolerability of nefazodone. Twenty-six depressed subjects, 21-63 years old, were recruited at the Massachusetts General Hospital. Thirteen subjects (50%) had discontinued an SSRI within 1-4 weeks due to ineffectiveness and/or side effects. Thirteen subjects (50%) had not taken antidepressants for the previous 6 months. Subjects were administered open nefazodone 50 mg p.o. b.i.d., and doses were increased as tolerated to a maximum of 600 mg/day. Subjects were followed for 12 weeks and were assessed for response and side effects using HAM-D-6 and clinical interviews. Both groups improved significantly on nefazodone; however, there was no statistically significant difference in response (>or=50% decrease in HAM-D-6) rates between completers with prior SSRI treatment (80%) and completers without recent exposure to antidepressants (67%). Response rates based on intent-to-treat (ITT) analysis were 31% for both groups. Association between prior SSRI treatment and discontinuation of nefazodone due to side effects or non-response was not statistically significant. Our study suggests that the rate of negative outcomes with nefazodone is no different whether patients have recently failed an SSRI.

Adult↗
PubMed2004

Gefitinib: phase II and III results in advanced non-small cell lung cancer.

Several novel biologic agents have been designed to specifically inhibit different aspects of tumor growth and progression. The epidermal growth factor receptor has a pivotal role in tumor biology and thus is an important anticancer target. Gefitinib is an orally active epidermal growth factor receptor tyrosine kinase inhibitor that blocks signal-transduction pathways implicated in the proliferation and survival of cancer cells. Clinically meaningful antitumor activity, symptom relief, and a good tolerability profile have been shown in phase II trials of gefitinib monotherapy in patients with recurrent non-small cell lung cancer. Clinical trials are ongoing to investigate further applications of this novel agent for the treatment of non-small cell lung cancer.

Antineoplastic Agents↗
PubMed2004

Challenges in defining and identifying patients with non-small cell lung cancer and poor performance status.

Performance status (PS), a subjective measure of the functional status of a patient with cancer and his or her ability to perform normal activities, is influenced both by tumor-related and by comorbidity-related factors. It is a reliable independent prognostic indicator for survival in patients with advanced non-small cell lung cancer. Patients with a poor PS (PS2) constitute up to 30% to 40% of the population of patients with advanced non-small cell lung cancer, yet they are underrepresented in clinical trials. These patients are heterogeneous, which makes it challenging to use their PS scores alone to guide their therapy. A greater understanding of PS scores and the factors that affect them can be gained through PS2-specific clinical trials, which can lead to the development of better PS instruments to aid in making therapeutic decisions.

Carcinoma, Non-Small-Cell Lung↗
PubMed2004

Treatment of thymoma: a comparative study between Thailand and the United States and a review of the literature.

This article provides a unique perspective on thymoma by describing the clinical scenarios from 2 diverse patient populations followed by an update. A comparative chart review was conducted on patients diagnosed at 2 university-based hospitals, 1 in the United States and 1 in Thailand. A comprehensive review of the literature was then performed through MEDLINE for articles between 1980 and 2002. During the last 23 years, charts from 16 patients at each institution were available for review. The most common presenting symptoms were myasthenia gravis (47%), dyspnea (25%), and chest discomfort (19%) and are similar to those reported in the literature. The primary treatment of stages I-III disease included surgery with or without radiation. Trimodality therapy with surgery, radiotherapy, and chemotherapy was pursued in 43% of patients with stage IV disease in the United States, whereas no patients from Thailand underwent this regimen. Median overall survivals were 124 and 76 months in the Thai and the US groups, respectively (P = 0.76). No major differences in the clinical features were observed between the 2 institutions, although a trend toward more advanced disease was seen in the United States. Surgery and radiation remain the backbone of treatment, but the role for chemotherapy is increasing.

Adult↗
PubMed2003

Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial.

CONTEXT: More persons in the United States die from non-small cell lung cancer (NSCLC) than from breast, colorectal, and prostate cancer combined. In preclinical testing, oral gefitinib inhibited the growth of NSCLC tumors that express the epidermal growth factor receptor (EGFR), a mediator of cell signaling, and phase 1 trials have demonstrated that a fraction of patients with NSCLC progressing after chemotherapy experience both a decrease in lung cancer symptoms and radiographic tumor shrinkages with gefitinib. OBJECTIVE: To assess differences in symptomatic and radiographic response among patients with NSCLC receiving 250-mg and 500-mg daily doses of gefitinib. DESIGN, SETTING, AND PATIENTS: Double-blind, randomized phase 2 trial conducted from November 2000 to April 2001 in 30 US academic and community oncology centers. Patients (N = 221) had either stage IIIB or IV NSCLC for which they had received at least 2 chemotherapy regimens. INTERVENTION: Daily oral gefitinib, either 500 mg (administered as two 250-mg gefitinib tablets) or 250 mg (administered as one 250-mg gefitinib tablet and 1 matching placebo). MAIN OUTCOME MEASURES: Improvement of NSCLC symptoms (2-point or greater increase in score on the summed lung cancer subscale of the Functional Assessment of Cancer Therapy-Lung [FACT-L] instrument) and tumor regression (>50% decrease in lesion size on imaging studies). RESULTS: Of 221 patients enrolled, 216 received gefitinib as randomized. Symptoms of NSCLC improved in 43% (95% confidence interval [CI], 33%-53%) of patients receiving 250 mg of gefitinib and in 35% (95% CI, 26%-45%) of patients receiving 500 mg. These benefits were observed within 3 weeks in 75% of patients. Partial radiographic responses occurred in 12% (95% CI, 6%-20%) of individuals receiving 250 mg of gefitinib and in 9% (95% CI, 4%-16%) of those receiving 500 mg. Symptoms improved in 96% of patients with partial radiographic responses. The overall survival at 1 year was 25%. There were no significant differences between the 250-mg and 500-mg doses in rates of symptom improvement (P =.26), radiographic tumor regression (P =.51), and projected 1-year survival (P =.54). The 500-mg dose was associated more frequently with transient acne-like rash (P =.04) and diarrhea (P =.006). CONCLUSIONS: Gefitinib, a well-tolerated oral EGFR-tyrosine kinase inhibitor, improved disease-related symptoms and induced radiographic tumor regressions in patients with NSCLC persisting after chemotherapy.

Administration, Oral↗
PubMed2003

Zones of prevention: the geography of fall injuries in the elderly.

Our investigation of the geography of fall injuries considers the relationship between injury prevention and contextual approaches to health research. We use a geographic information system (GIS) to describe the pattern of emergency department reported falls of the elderly in the Capital Health Region, an administrative health area in Alberta, Canada. We used empirical Bayes estimates to obtain a geographic measure of fall incidence over the study area and a cluster detection statistic to measure the presence of a significant spatial cluster in the region. Inner-city Edmonton had the highest incidence of risk, suburban Edmonton the lowest, and surrounding rural regions and smaller communities had more moderate fall incidence. We argue that descriptive geography can enhance the effectiveness of injury prevention programs by identifying zones of high risk, even when the individual-level and contextual factors that explain the underlying patterns are unknown.

Accidental Falls↗
PubMed2003

Treatment of non-small-cell lung cancer in older persons.

The majority of individuals diagnosed with lung cancer in the United States are 70 years of age and older. Defining appropriate therapy for older patients with non-small-cell lung cancer (NSCLC) is becoming a major focus of clinical research. In this article, we review the available data on clinical predictors of risk and benefit for elderly NSCLC patients receiving treatment via a variety of modalities, including surgery, radiotherapy, combined radiotherapy and chemotherapy, and chemotherapy alone. The data demonstrate that subgroups of elderly patients benefit from appropriately selected treatment. Participation of older patients in clinical trials designed to assess efficacy, toxicity, and quality-of-life outcomes for recently developed treatment modalities in this population is critical.

Age Factors↗
PubMed2003

The benefits of achieving stable disease in advanced lung cancer.

The cytostatic, molecular-targeted therapies becoming available for lung cancer and other human solid tumors are more likely to result in stable disease than to produce tumor regression. In the setting of advanced lung cancer, stable disease provides significant benefit to the patient. However, in the context of clinical trials, stable disease is vaguely defined, difficult to measure, and may represent a heterogeneous patient population. The inclusion of alternative trial end points such as symptom improvement and biologic activity may help to identify patients who have achieved clinically relevant stable disease. The epidermal growth factor receptor-tyrosine kinase inhibitor gefitinib (Iressa) has been shown to produce partial responses and stable disease in patients with advanced lung cancer who have previously received treatment with standard chemotherapies. In the monotherapy trials of gefitinib, stable disease was correlated with improvements in disease-related symptoms and quality of life--the most meaningful end points for the patient with advanced lung cancer. Thus, with the introduction of new molecular-targeted agents, stable disease with clinical benefit should become an important goal of anticancer therapy.

Antineoplastic Agents↗
PubMed2002

Economic analysis of vinorelbine plus cisplatin versus paclitaxel plus carboplatin for advanced non-small-cell lung cancer.

BACKGROUND: It is increasingly important to have timely information about the economic impact of new cancer therapies in today's cost-conscious environment. Nearly 170 000 people are diagnosed with lung cancer annually in the United States. We performed an economic analysis alongside Southwest Oncology Group Trial S9509 to estimate the cost-effectiveness of cisplatin plus vinorelbine versus carboplatin plus paclitaxel for patients with advanced non-small-cell lung cancer. There were no statistically significant differences in survival or cancer-related quality of life between the treatment arms. METHODS: Use of both protocol and nonprotocol lung cancer-related health care was tracked for 24 months from the initiation of therapy. To determine expenditures, nationally standardized costs were applied to each type of health care service used, and these were summed over time. Lifetime expenditures and 95% confidence intervals (CIs) for each arm of the trial were calculated with the use of a multivariate regression technique that accounts for censoring. Student's t tests were used to compare the difference in costs between the arms. All statistical tests were two-sided. RESULTS: Cancer-related health care costs over the period of observation averaged 40,292 dollars (95% CI = 36,226 dollars to 44,359 dollars) for patients in the cisplatin plus vinorelbine arm versus 48,940 dollars (95% CI = 44,674 dollars to 53,208 dollars) for patients in the carboplatin plus paclitaxel arm (P =.004), with a mean difference of 8648 dollars (95% CI = 2634 dollars to 14,662 dollars). Protocol chemotherapy drugs and medical procedures costs were statistically significantly higher in the paclitaxel arm (P =.0003 and P<.0001, respectively), whereas protocol chemotherapy delivery costs were statistically significantly higher in the vinorelbine arm (P<.0001). There was no difference between the arms in costs for blood products, supportive care medications, nonprotocol-related inpatient or outpatient care, and nonprotocol chemotherapy. CONCLUSIONS: Treatment with carboplatin plus paclitaxel is substantially and statistically significantly more expensive than treatment with cisplatin plus vinorelbine. The majority of the cost difference is due to the additional cost of the protocol chemotherapy (approximately 12,000 dollars). Notable differences in costs of downstream health care were not apparent.

Adult↗
PubMed2002

Preclinical and clinical studies of docetaxel and exisulind in the treatment of human lung cancer.

Lung cancer is the leading cause of cancer death in the United States. The majority of patients with non-small cell lung cancers present with inoperable disease because of the presence of metastases to regional lymph nodes or other metastatic sites. About one third of patients have stage IV disease with metastases to distant organs at the time of diagnosis. The prognosis for these patients is very poor. With best supportive care the median survival is only 4 months and the 1-year survival rate is 10% to 15%. Current chemotherapy combinations improve the survival and quality of life for patients with advanced non-small cell lung cancer. With two-drug combinations, median survival is increased to 8 months or more and 1-year survival is increased to 35% to 40%. Still, complete response rates are low and more than 80% of patients die within 1 year of diagnosis. The improvements created by current therapies led to studies of chemotherapy in the second-line setting. Docetaxel has been shown to improve survival of patients who failed platinum-based chemotherapy and was approved by the U.S. Food and Drug Administration for therapy in this setting. However, response rates were very low and survival very short. Therefore, new therapies are urgently needed. Exisulind is a novel oral anticancer agent that holds promise for the treatment of patients with advanced non-small cell lung cancer. Exisulind was originally developed as a chemoprevention agent for colorectal cancer. Preclinical studies showed that exisulind could prevent polyp formation and inhibit the growth of colorectal cancers. Subsequent preclinical studies showed that exisulind also inhibited the growth of human breast, prostate, and lung cancers. Phase I clinical studies showed that twice-daily oral doses could be given safely and would provide peak concentrations that were equivalent to those required for in vitro effects. These observations lead to the studies of the combination of exisulind and docetaxel in preclinical and clinical studies in human lung cancer described in this article.

Administration, Oral↗
PubMed2002

Randomized controlled trial with low-dose spiral CT for lung cancer screening: feasibility study and preliminary results.

PURPOSE: To assess the feasibility of conducting a randomized controlled trial for lung cancer screening. MATERIALS AND METHODS: Subjects are being recruited into a randomized controlled trial to undergo either low-dose spiral computed tomography (CT) or observation. Subjects are from a high-risk group with known chronic obstructive pulmonary disease and sputum atypia and a moderate-risk group randomly selected from the general population of a Veterans Affairs Medical Center. All subjects must be 50-80 years of age with 30 or more pack-years of cigarette smoking and must not have undergone chest CT during the previous 3 years. Baseline screening CT is performed with 50 mA, 120 kVp, 5-mm collimation, and a pitch of 2. CT scan interpretation and management of nodules is based on Society of Thoracic Radiology guidelines. The chi(2) test for categoric data was used for statistical analysis. RESULTS: To date, 304 eligible subjects have been contacted, and 239 (79%) have agreed to participate in the trial. One hundred nineteen (88%) of the 136 subjects in the high-risk group and 120 (71%) of the 168 subjects in the moderate-risk group agreed to randomization (P <.001). To date, 190 subjects have been randomized. Of the first 92 subjects examined with CT, 22 (40%) of 55 in the high-risk group and eight (22%) of 37 in the moderate-risk group had one to six noncalcified nodules that required follow-up (P =.07). In all but three subjects, nodules were smaller than 5 mm. Two of the three larger nodules were malignancies. CONCLUSION: Findings of this study indicate that a randomized controlled trial of CT to screen for lung cancer is feasible.

Aged↗