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Biomedical subjects

R D Gelber

Publications and source records attributed to R D Gelber.

At least 91 records · Page 5Linked to original sources
PubMed1995

A quality-adjusted survival meta-analysis of adjuvant chemotherapy for premenopausal breast cancer. International Breast Cancer Study Group.

The purpose of this paper is to develop and apply a meta-analysis methodology, that does not require patient-level data, for comparing treatments in terms of quality-of-life-adjusted survival. As a motivating example, we considered adjuvant chemotherapy for breast cancer. This therapy has been shown to offer an improvement in recurrence-free and overall survival, especially for younger women, but its acute toxic effects discourage some physicians from prescribing it. To determine whether the benefit of adjuvant chemotherapy treatment outweighs its costs in terms of toxic effects, we performed a meta-analysis of quality-adjusted survival based on data from 1229 patients, 49 years of age or younger, randomized in eight clinical trials that compared chemotherapy versus no adjuvant systemic therapy. We conducted the meta-analysis by performing a quality-adjusted survival analysis known as a Q-TWiST analysis on each trial. A Q-TWiST analysis allows one to make treatment comparisons that incorporate differences in quality of life associated with various health states. In this analysis, we define as health states the periods of time patients spend: (i) with subjective toxic effects of chemotherapy; (ii) without symptoms of recurrence and toxicity, and (iii) following disease recurrence. We assigned weights to each health state which reflect their relative value in terms of quality of life and allowed them to vary in a sensitivity analysis. We then combined the individual trial results in a meta-analysis, using a multivariate regression model, in such a way that we could easily perform an overall sensitivity analysis. Individual patient-level data are not required to perform this meta-analysis methodology if the individual Q-TWiST analysis results for each trial are available.

Adult↗
PubMed1995

Female sex and higher drug dose as risk factors for late cardiotoxic effects of doxorubicin therapy for childhood cancer.

BACKGROUND: Late cardiotoxic effects of doxorubicin are increasingly a problem for patients who survive childhood cancer. Cardiotoxicity is often progressive, and some patients have disabling symptoms. Our objective was to identify risk factors for late cardiotoxicity. METHODS: We examined echocardiograms from 120 children and adults who had received cumulative doses of 244 to 550 mg of doxorubicin per square meter of body-surface area for the treatment of acute lymphoblastic leukemia or osteogenic sarcoma in childhood, a mean of 8.1 years earlier. Measurements of blood pressure and left ventricular function, contractility (measured as the stress-velocity index), end-diastolic posterior-wall thickness, end-diastolic dimension, mass, and afterload (measured as end-systolic wall stress) were compared with sex-specific values from a cohort of 296 normal subjects. RESULTS: All echocardiographic measurements were abnormal at follow-up a minimum of two years after the end of therapy, with more frequent and severe abnormalities in female patients. In a multivariate analysis, female sex and a higher cumulative dose of doxorubicin were associated with depressed contractility (P < or = 0.001), and there was an interaction between these two variables. Independent and significant associations were found between a higher rate of administration of doxorubicin and increased afterload (P < or = 0.001), left ventricular dilatation, and depressed left ventricular function; between a higher cumulative dose and depressed left ventricular function (P < or = 0.001); between a younger age at diagnosis and reduced left-ventricular-wall thickness and mass and increased afterload; and between a longer time since the completion of doxorubicin therapy and reduced left-ventricular-wall thickness and increased afterload (P < or = 0.001). CONCLUSIONS: Female sex and a higher rate of administration of doxorubicin were independent risk factors for cardiac abnormalities after treatment with doxorubicin for childhood cancer; the prevalence and severity of abnormalities increased with longer follow-up.

Adolescent↗
PubMed1995

Measuring patient-centered outcomes in neurologic disease. Extending the Q-TWiST method.

BACKGROUND: Current clinical research and outcomes assessment on multiple sclerosis rely on an approach to disability measurement that is heavily influenced by ambulation. Not only is this strategy often insensitive to the clinical changes affected by pharmacotherapeutic or rehabilitative interventions but it also disregards the symptoms that patients seem to consider most enervating. We propose a new method for evaluating clinical interventions in terms of their impact on the symptoms of multiple sclerosis, side effects, parameters of exacerbation, and disease progression, while considering the patient's perspective. METHODS: The extended Q-TWiST method yields an estimation of treatment trade-offs in terms of Quality-adjusted Time Without Symptoms and Toxicities (Q-TWiST). An illustration of this method is presented by using a hypothetical clinical trial of two treatments. The trade-offs between the two treatments are highlighted to facilitate treatment decision making by using individual patient importance weights. CONCLUSION: We discuss applications to other clinical research and other chronic diseases.

Clinical Trials as Topic↗
PubMed1995

The Q-TWiST approach to assessing health-related quality of life in epilepsy.

We propose to develop a methodology for evaluating clinical interventions for epilepsy in terms of their effects on disease-related outcomes, social cost and quality of life, while incorporating patient preference. The technique represents an extension of the 'quality-adjusted time without symptoms and toxicities' (Q-TWiST) method, which has been previously used to evaluate treatments for cancer and AIDS with respect to their costs in terms of toxicities, and benefits in terms of improved progression-free and overall survival. The extensions we propose to develop allow additional dimensions of quality of life relevant to epilepsy to be included in the analysis. We demonstrate a possible application of the proposed Q-TWiST method with a hypothetical example comparing surgery vs antiepileptic medication management alone for seizure control. The trade-offs between these alternative treatments are highlighted, along with patient importance weightings regarding various dimensions of quality of life. We describe further research needed to develop the methodology fully and comment on its potential usefulness.

Anticonvulsants↗
PubMed1995

Routine tests during follow-up of patients after primary treatment for operable breast cancer. International (Ludwig) Breast Cancer Study Group (IBCSG)

BACKGROUND: Follow-up tests for patients after diagnosis and primary treatment of breast cancer are routinely performed. However, the usefulness of these follow-up parameters remains unclear. We determined the yield of a variety of blood tests used to detect the presence of overt metastatic disease. METHODS: 4105 patients enrolled in International (Ludwig) Breast Cancer Study Group (IBCSG) randomized clinical trials from 1978 to 1985 were analyzed for abnormal or equivocal findings in six routine blood tests obtained every 3 months for the first two years, every six months for years 3-5 and yearly thereafter. The relationship of test results to the occurrence of overt metastatic disease was evaluated. The relapses were categorized as follows in order to estimate the yield of the different tests for relevant sites of metastases: any breast cancer relapse, bone +/- other; liver +/- other. RESULTS: Alkaline phosphatase alone was abnormal in a high proportion of patients with either bone metastases, liver metastases, or both. SGOT and gamma-GT were also sensitive for patients with liver metastases. Bilirubin, serum calcium, and serum creatinine were relatively insensitive indicators of relapse. Abnormal test results were reported sometime during a patient's disease-free period for 3% to 6% of patients, depending on the test. CONCLUSIONS: Alkaline phosphatase was the most effective blood test to distinguish patients with relapse from those without relapse. It is inexpensive and its yield is relatively high for predicting liver and bone metastases. The routine use of the other tests analyzed to detect metastases was not justified.

Breast Neoplasms↗
PubMed1994

A controlled trial of intravenous immune globulin for the prevention of serious bacterial infections in children receiving zidovudine for advanced human immunodeficiency virus infection. Pediatric AIDS Clinical Trials Group.

BACKGROUND: Serious bacterial infections are common in children infected with the human immunodeficiency virus (HIV). Studies performed before zidovudine became standard therapy found that intravenous immune globulin decreases the number of serious bacterial infections in these children. We designed a multicenter study to evaluate the efficacy of intravenous immune globulin in children with advanced HIV infection who were receiving zidovudine. METHODS: In a double-blind trial 255 children between 3 months and 12 years of age who had the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex were randomly assigned to receive either intravenous immune globulin (400 mg per kilogram of body weight) (n = 129) or placebo (0.1 percent albumin) (n = 126) every 28 days. All children received 180 mg of zidovudine per square meter of body-surface area orally four times daily. Treatment assignment was stratified according to whether the patients had a history of one or more serious bacterial infections, had previously been treated with zidovudine, or were currently receiving prophylaxis with trimethoprim-sulfamethoxazole. The median length of follow-up was 30.6 months. RESULTS: The estimated two-year rates of serious bacterial infections with confirmed pathogens were 16.9 percent for the immune globulin group and 24.3 percent for the placebo group (relative risk, 0.60; 95 percent confidence interval, 0.35 to 1.04; P = 0.07). The treatment effect was seen primarily among the 174 children who were not receiving trimethoprim-sulfamethoxazole prophylaxis at entry; the estimated two-year rates of infection were 11.3 percent for the immune globulin group and 26.8 percent for the placebo group (relative risk, 0.45; 95 percent confidence interval, 0.22 to 0.91; P = 0.03). For the 81 children who were receiving trimethoprim-sulfamethoxazole prophylaxis initially, the rates were 27.7 percent in the immune globulin group and 17.7 percent in the placebo group (relative risk, 1.26; 95 percent confidence interval, 0.44 to 3.66; P = 0.67). The two-year survival was similar in the two groups: 79.2 percent among immune globulin recipients and 75.4 percent among placebo recipients (P = 0.41). CONCLUSIONS: In children with advanced HIV disease who are receiving zidovudine, intravenous immune globulin decreases the risk of serious bacterial infections. However, this benefit is apparent only in children who are not receiving trimethoprim-sulfamethoxazole as prophylaxis.

AIDS-Related Complex↗
PubMed1994

Present and future projects of the International Breast Cancer Study Group.

The International Breast Cancer Study Group (formerly the Ludwig Group) has conducted nine clinical trials since 1978 (see the Appendix for participants and authors). Biologic hypotheses related to the combined use of chemotherapy and endocrine therapy in women with operable breast cancer were tested. Questions of timing of chemotherapy with respect to tumor surgery and late introduction of chemotherapy were also evaluated. Ongoing and future trials continue in this tradition to investigate combinations of available endocrine therapies and cytotoxic agents.

Aged↗
PubMed1994

Evaluation of the quality of life associated with zidovudine treatment in asymptomatic human immunodeficiency virus infection. The AIDS Clinical Trials Group.

BACKGROUND: Zidovudine therapy is recommended for asymptomatic patients infected with the human immunodeficiency virus (HIV) who have fewer than 500 CD4+ cells per cubic millimeter. An analysis of the quality of life associated with therapy that integrated both the effects of adverse events and the benefits of delayed disease progression might influence this recommendation. METHODS: We applied a survival analysis adjusted for the quality of life to data from a randomized trial conducted by the AIDS Clinical Trials Group. The trial compared treatment with 500 mg of zidovudine per day, 1500 mg of zidovudine per day, and placebo (Protocol 019) in 1338 asymptomatic HIV-infected patients. RESULTS: The average time with neither a progression of disease nor an adverse event (symptom or laboratory finding) was 15.7, 15.6, and 14.8 months for patients receiving placebo, 500 mg of zidovudine, and 1500 mg of zidovudine, respectively. The incidence of severe symptoms was 13.8 percent in the placebo group, 15.2 percent in the 500-mg group, and 19.9 percent in the 1500-mg group (P = 0.038). After 18 months, the 500-mg group gained an average of 0.5 months without disease progression, as compared with the placebo group, but had severe adverse events an average of 0.6 months sooner. The 500-mg group had more quality-of-life--adjusted time than the placebo group only if the time lived after the progression of disease was considered by a patient to have less value than the time after the occurrence of a severe symptom. CONCLUSIONS: For asymptomatic patients treated with 500 mg of zidovudine, a reduction in the quality of life due to severe side effects of therapy approximately equals the increase in the quality of life associated with a delay in the progression of HIV disease.

CD4-Positive T-Lymphocytes↗
PubMed1994

Effect of systemic adjuvant treatment on first sites of breast cancer relapse.

Adjuvant systemic treatment for resectable breast cancer changes the natural history of the disease but provides only a small and delayed effect on survival. Evaluation of the types of first relapse avoided by available treatments may explain why effects on mortality are small and appear late during follow-up. In randomised clinical trials done by the International Breast Cancer Study Group (IBCSG) between 1978 and 1985, 2108 patients with node-positive disease received more-effective treatments (6 or more cycles of cyclophosphamide, methotrexate, fluorouracil and prednisone; with or without tamoxifen, or tamoxifen and prednisone alone), and 722 patients received less-effective treatments (no treatment or a single cycle of chemotherapy). 3 main categories of first site of relapse were defined and evaluated by cumulative incidence analysis: local or regional, and distant soft tissue, bone, and viscera. The more-effective treatments reduced the cumulative incidence of first relapse in local or regional and distant soft tissue sites at 10 years from 36% to 18% (p = 0.0001); first relapse in bone and viscera was not altered by the more-effective treatments. These results were similar for premenopausal and postmenopausal women, and for patients with oestrogen-receptor-positive or oestrogen-receptor-negative tumours. Adjuvant systemic treatments in current use improve patient outcome mainly by reducing the incidence of first local or regional and distant soft-tissue relapses, while first recurrences in bone or viscera are influenced much less. More intensive treatments at present being tested in clinical trials might affect bone and visceral relapses and have a greater and earlier influence on survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Timing of baseline quality of life assessment in an international adjuvant breast cancer trial: its effect on patient self-estimation. The International Breast Cancer Study Group.

BACKGROUND: Variability in timing of baseline quality of life (QL) assessments in two ongoing International Breast Cancer Study Group (IBCSG) randomized clinical trials occurred as a result of allowing some flexibility in the timing. This retrospective report describes the QL timing in relation to surgery and start of adjuvant therapy and its effect on QL self-estimation. PATIENTS AND METHODS: Self-administered measures of baseline QL were obtained on day 1 of adjuvant therapy or as close to that date as possible from 1389 pre- and post-menopausal women with operable breast cancer. RESULTS: Fifty-four percent of QL assessments were done on day 1 of adjuvant therapy, 18% before day 1 and 28% after. An ANOVA, controlling for surgery, institution and language, showed that: for patients receiving endocrine therapy alone, QL improved as time from surgery increased, but start of adjuvant treatment had no effect, while for chemotherapy patients, appetite, physical well-being and, in pre-menopausal patients, coping were worse 1 to 5 days after the start of treatment. Chemotherapy had little effect on mood and emotional well-being. CONCLUSIONS: Timing of QL assessment in relation to diagnosis affects global adjustment measures; timing in relation to chemotherapy affects measures sensitive to toxicity. Timing is an important consideration in study conduct and data analysis.

Adult↗