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R D Gelber

Publications and source records attributed to R D Gelber.

At least 145 records · Page 8Linked to original sources
PubMed1991

Quality-of-life-adjusted evaluation of adjuvant therapies for operable breast cancer. The International Breast Cancer Study Group.

OBJECTIVE: To evaluate a single cycle of adjuvant chemotherapy compared with longer duration chemotherapy for premenopausal women or chemoendocrine therapy for postmenopausal women with operable breast cancer using a quality-of-life-oriented end point, Q-TWiST (quality-adjusted analysis of TWiST: Time Without Symptoms and Toxicity). DESIGN: Multicenter randomized clinical trial--International Breast Cancer Study Group (IBCSG: formerly Ludwig Group) Trial V. SETTING: IBCSG participating centers in Sweden, Switzerland, Australia, Yugoslavia, Spain, New Zealand, Italy, Germany, and South Africa. PATIENTS: Data were available for 1229 eligible patients with node-positive breast cancer who were randomized to receive one of three adjuvant treatments after at least a total mastectomy and axillary clearance. INTERVENTIONS: Patients received either a single cycle of perioperative chemotherapy consisting of cyclophosphamide, methotrexate, fluorouracil, and leucovorin; or six cycles (6 months) of a conventionally timed chemotherapy consisting of cyclophosphamide, methotrexate, fluorouracil, and prednisone for premenopausal women or this combination plus tamoxifen for postmenopausal women; or both perioperative and conventionally timed chemotherapy for a 7-month course of adjuvant therapy. RESULTS: At 5 years of median follow-up, patients who received the longer duration therapies had an improved 5-year disease-free survival percentage (53% compared with 36%; P less than 0.001) and 5-year overall survival percentage (73% compared with 63%; P = 0.001) compared with those who received the single perioperative cycle alone. By 3.5 years, the greater burden of toxic effects associated with the longer duration treatments was balanced by their superior control of disease. Within 5 years of follow-up, even after subtracting time with adjuvant treatment toxicity, patients gained an average of 2.2 months of Q-TWiST if treated with the longer duration therapies compared with the single cycle (P = 0.03). The gain for premenopausal patients was 2.8 months (P = 0.05), whereas the gain for postmenopausal women was 1.5 months (P greater than 0.2). CONCLUSIONS: Six or seven months of adjuvant chemotherapy or chemoendocrine therapy improve both the quantity and quality of life for patients with node-positive breast cancer compared with a single short course of perioperative combination chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Late cardiac effects of doxorubicin therapy for acute lymphoblastic leukemia in childhood.

BACKGROUND: Cardiotoxicity is a recognized complication of doxorubicin therapy, but the long-term effects of doxorubicin are not well documented. We therefore assessed the cardiac status of 115 children who had been treated for acute lymphoblastic leukemia with doxorubicin 1 to 15 years earlier in whom the disease was in continuous remission. METHODS: Eighteen patients received one dose of doxorubicin (45 mg per square meter of body-surface area), and 97 received multiple doses totaling 228 to 550 mg per square meter (median, 360). The median interval between the end of treatment and the cardiac evaluation was 6.4 years. Our evaluation consisted of a history, 24-hour ambulatory electrocardiographic recording, exercise testing, and echocardiography. RESULTS: Fifty-seven percent of the patients had abnormalities of left ventricular afterload (measured as end-systolic wall stress) or contractility (measured as the stress-velocity index). The cumulative dose of doxorubicin was the most significant predictor of abnormal cardiac function (P less than 0.002). Seventeen percent of patients who received one dose of doxorubicin had slightly elevated age-adjusted afterload, and none had decreased contractility. In contrast, 65 percent of patients who received at least 228 mg of doxorubicin per square meter had increased afterload (59 percent of patients), decreased contractility (23 percent), or both. Increased afterload was due to reduced ventricular wall thickness, not to hypertension or ventricular dilatation. In multivariate analyses restricted to patients who received at least 228 mg of doxorubicin per square meter, the only significant predictive factors were a higher cumulative dose (P = 0.01), which predicted decreased contractility, and an age of less than four years at treatment (P = 0.003), which predicted increased afterload. Afterload increased progressively in 24 of 34 patients evaluated serially (71 percent). Reported symptoms correlated poorly with indexes of exercise tolerance or ventricular function. Eleven patients had congestive heart failure within one year of treatment with doxorubicin; five of them had recurrent heart failure 3.7 to 10.3 years after completing doxorubicin treatment, and two required heart transplantation. No patient had late heart failure as a new event. CONCLUSIONS: Doxorubicin therapy in childhood impairs myocardial growth in a dose-related fashion and results in a progressive increase in left ventricular afterload sometimes accompanied by reduced contractility. We hypothesize that the loss of myocytes during doxorubicin therapy in childhood might result in inadequate left ventricular mass and clinically important heart disease in later years.

Child↗
PubMed1991

Adjuvant therapy of breast cancer. International Breast Cancer Study Group.

Adjuvant systemic therapy has been shown to reduce relapses in treated women and to prolong their survival. This is true for all studied subpopulations. Multidrug chemotherapy for the duration of 6 months for the premenopausal patients, and tamoxifen or short-term chemotherapy with long-term tamoxifen for the postmenopausal patients represent the treatments of choice to reduce the risk of relapse. Some of the high priority questions relate to i) the definition of a population for which the risk of relapse is low enough to avoid the use of systemic adjuvant therapy, and ii) the definition of an optimal way of using available adjuvant therapies. These might find answers from ongoing research. The modest but real improvement of the prognosis in operable breast cancer was exclusively obtained only by means of clinical trials, and it is mandatory that participation in programs of clinical research becomes medically and socially the treatment of choice.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Association of c-erbB-2 expression and S-phase fraction in the prognosis of node positive breast cancer.

An immunohistochemical study was performed on 211 primary breast carcinomas for c-erbB-2 expression. All patients had involvement of axillary lymph nodes and all were randomised onto one of the Ludwig Breast Cancer Trials I-IV between July 1978 and August 1981. c-erbB-2 overexpression significantly correlated with high S-phase fraction, four or more positive axillary nodes involved, estrogen receptor negative primaries, progesterone receptor negative primaries, high grade tumours and DNA aneuploidy. With a nine year median follow-up c-erbB-2 positive tumours had worse disease-free survival (p = 0.0002) and overall survival (p less than 0.0001). Multivariate analyses using proportional hazard regression models demonstrated that c-erbB-2 positivity continued to predict a poor outcome even when accounting for the effects of other prognostic factors.

Antibodies, Monoclonal↗
PubMed1991

Meta-analysis: the fashion of summing-up evidence. Part I. Rationale and conduct.

Meta-analysis is the process of formally combining the quantitative results of separate studies in order to increase the statistical precession of estimated effects. It has become fashionable when individual studies fail to yield conclusive results. A recent update of a meta-analysis (overview) for treatments of patients with early breast cancer motivated this commentary to discuss the rationale, principles of conduct, statistical methods, and graphical display for summing up results. In part II we will approach the issue of interpretation and use of overview data.

Bayes Theorem↗
PubMed1990

Quality adjusted survival analysis.

We present a technique, quality adjusted survival analysis, for the analysis of controlled trials where patients may experience several health states which differ in their quality of life. When the data are censored, a survival analysis of the quality adjusted life years achieved may involve informative censoring, and produce biased estimates. To overcome this, we partition the survival curve; the resulting areas, which represent the mean time in each state, are multiplied by utility weights to provide an unbiased estimate of (restricted) quality adjusted survival. If the appropriate weights are in doubt, the results are best presented as a threshold analysis over the utility weights, allowing individual recommendation to be read from a simple graph. The certainty of the conclusions can be presented as confidence bands on the threshold line. The techniques are illustrated with a re-analysis of a large three-arm trial of adjuvant chemoendocrine therapy for stage II breast cancer in postmenopausal women. This shows that if the value of time spent in toxicity is greater than the time spent in relapse, we can be 95 per cent confident that chemoendocrine therapy is the preferred option.

Breast Neoplasms↗
PubMed1990

More is better! Update of Dana-Farber Cancer Institute/Children's Hospital childhood acute lymphoblastic leukemia trials.

Between 1973 and 1985, 553 children with childhood acute lymphoblastic leukemia were treated on Dana-Farber Cancer Institute/Children's Hospital, Boston, protocols. The programs featured intensive remission induction therapy, CNS treatment with cranial irradiation and intrathecal drugs, doxorubicin intensification with or without asparaginase, and 2-21/2 years of conventional continuation therapy. There has been progressive improvement in event-free survival for each successive program. Leukemia control concerns pertain to: 1. late relapses (at greater than 5 years) in "standard-risk" patients; 2. an increased incidence of CNS relapses, especially in "standard-risk" patients, as preventative treatment is reduced in intensity; and 3. bone marrow relapses in "high-risk"patients. Comparisons of patients receiving the more intensive arm of each protocol with those receiving the less intensive arm support the hypothesis that more intensive chemotherapy results in improved event-free survival.

Adolescent↗
PubMed1990

The magnitude of endocrine effects of adjuvant chemotherapy for premenopausal breast cancer patients. The International Breast Cancer Study Group.

We analysed the incidence of amenorrhoea and its association with outcome in a cohort of 1127 premenopausal women with breast cancer randomized to International Trial V (formerly Ludwig V). For 552 patients without axillary lymph node involvement, one course of perioperative cytotoxic drugs was compared with no-adjuvant chemotherapy. For 575 patients with node-positive disease, a single course of cytotoxic chemotherapy was compared with a prolonged treatment (6 or 7 courses). Amenorrhoea was defined as having no menstrual bleeding for a 3-month interval within the first 9 months after surgery. Amenorrhoea was observed in 21% of the 199 patients with node-negative breast cancer who received no adjuvant therapy, 31% of the 353 node-negative patients who had a single course of cytotoxic therapy, 31% of the 188 patients with node-positive disease who had the same short-duration therapy, and 68% of the 387 node-positive patients who had a prolonged adjuvant therapy. Amenorrhoea was associated with an increased disease-free survival (DFS) only in the patients with prolonged cytotoxic therapy: 4-year DFS % (+/- s.e.) was 68% +/- 3% vs. 61% +/- 5% for the amenorrhoea and the no-amenorrhoea groups, respectively, (p = 0.05). In contrast, the comparison between prolonged therapy and one single course among node-positive patients showed a much larger treatment effect (4-year DFS 66% vs. 38%, p less than 0.0001). We conclude that although cytotoxics-induced amenorrhoea is associated with a better outcome, it is unlikely that this form of endocrine manipulation is the main mechanism of response to adjuvant systemic chemotherapy.

Adult↗
PubMed1990

c-erbB-2 protein expression in node negative breast cancer.

We investigated the expression of c-erB-2 protein in two matched groups of breast cancer patients, one with and one without relapse. 37 patients with relapse were compared with 42 patients without recurrence for time of observation, adjuvant treatment, age, menopausal status and estrogen receptor content. Paraffin-embedded sections were stained with the polyclonal antibody 21N, raised against a synthetic peptide from the predicted sequence of the c-erbB-2 protein. The staining of c-erbB-2 was measured on a scale of 0 to 3+. C-erbB-2 staining was negative in 16 (38%) patients in the relapse-free group, and in 8 (22%) of the patients with metastases. Neither disease-free survival (DFS) nor overall survival (OS) were dependent upon the extent of c-erbB-2 expression. An analysis by estrogen receptor (ER) status (i.e. positive or negative) and by c-erbB-2 expression (i.e. positive or negative) revealed that patients with ER-positive primaries and negative c-erbB-2 have the longest disease-free survival (DFS) and overall survival (OS). We conclude that c-erbB-2 expression might be clinically useful only if other prognostic variables (e.g. estrogen receptor content in the tumor) are also considered.

Adult↗
PubMed1990

Bone marrow transplantation for myelodysplasia and secondary acute nonlymphoblastic leukemia.

Twenty-three patients with primary myelodysplasia (MDS) or secondary myelodysplasia/acute nonlymphocytic leukemia (MDS/ANLL) were treated with allogeneic or syngeneic bone marrow transplantation (BMT). Only one patient was in a chemotherapy-induced hematologic remission. Graft-versus-host disease prophylaxis included methotrexate, methotrexate plus cyclosporine, cyclosporine, or T-cell depletion using one of two anti-CD5 monoclonal antibodies. For patients with primary MDS, the median age was 19 years (range, 11 to 41 years) and the actuarial disease-free survival was 56% +/- 21% (median follow-up, 2 years; range, 0.8 to 5 years). There were three graft failures (two with autologous recovery) and two early deaths. Outcome appeared to be related to French-American-British (FAB) classification. For patients with secondary MDS/ANLL, the median age was 28 years (range, 3 to 16 years) and the actuarial disease-free survival was 27% +/- 13% (median follow-up, 5 years; range, 2.5 to 8.5 years). There were no graft failures, two relapses, and four early deaths. The presence of marrow fibrosis per se did not predict for graft failure (P = .21); however, the use of T-cell depleted marrow in patients with marrow fibrosis resulted in graft failure in three of five individuals. Our results suggest that in patients with primary MDS or secondary MDS/ANLL, BMT should be considered early in the course of the disease, and that attempts at inducing a remission prior to BMT appeared to be unnecessary. In MDS patients with marrow fibrosis, T-cell depletion should be avoided.

Actuarial Analysis↗
PubMed1990

Adjuvant systemic therapy for breast cancer in the elderly: competing causes of mortality. International Breast Cancer Study Group.

Between 1978 and 1981 we conducted a trial in which adjuvant endocrine therapy consisting of tamoxifen (T = 20 mg/d) and low-dose prednisone (p = 7.5 mg/d) for the duration of one year (p + T), was compared with no adjuvant therapy (observation) in 320 women with operable breast cancer aged 66 to 80 years (median age, 70 years). All patients had axillary lymph node metastases after at least a total mastectomy and axillary clearance. At 96 months median follow-up, 9.1% of the patients died without apparent relapse from cancer. An additional 1.9% had a second malignant neoplastic disease (not breast cancer). The 8-year disease-free survival (DFS) percentages (+/- SE) for the p + T and the observation groups were 36% (+/- 4%), and 22% (+/- 3%), (P = .004). The 8-year overall survival percentages were 49% (+/- 4%) and 42% (+/- 4%), respectively (P = .43). We conclude that despite a large proportion of deaths without relapse of breast cancer, a significant advantage for the p + T group in terms of DFS was demonstrated. We hypothesize that an endocrine therapy of longer duration might have an overall survival benefit in a population of elderly patients.

Aged↗
PubMed1989

Prognostic implications of cytogenetic studies in an intensively treated group of children with acute lymphoblastic leukemia.

We assessed the prognostic significance of leukemia cell cytogenetics by analyzing bone marrow aspirates obtained at time of diagnosis in 165 children on a single protocol for acute lymphoblastic leukemia (ALL). These children were assigned to six mutually exclusive cytogenetic categories as follows: (1) hyperdiploid, with 50 or more chromosomes (n = 35); (2) hyperdiploid, with 47 to 49 chromosomes (n = 11); (3) diploid (n = 42); (4) pseudodiploid (n = 34); (5) hypodiploid (n = 9); and (6) insufficient data (n = 34). At a median follow-up of 5 years, there were no statistically significant differences between any of these cytogenetic categories in either event-free or overall survival. Those children with chromosomal translocations (n = 26) appeared to fare the same as those lacking translocations (n = 105). The absence of karyotypic prognostic significance was observed not only within the overall group, but also when the results were stratified by standard-risk and high-risk status. Of the specific structural chromosome changes that we studied, only the Philadelphia chromosome (Ph) appeared to confer a poor prognosis, although there were too few such cases to achieve statistical significance. Although we did not detect the event-free survival differences that have been described previously in hyperdiploid, hypodiploid, and pseudodiploid childhood ALL, our findings must be viewed as preliminary given the small number of children in some of the cytogenetic categories. We think that the prognostic implications of these cytogenetic features might have been nullified by improvements in therapy.

Adolescent↗