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Biomedical subjects

A Goldhirsch

Publications and source records attributed to A Goldhirsch.

At least 199 records · Page 11Linked to original sources
PubMed1992

Prognostic importance of c-erbB-2 expression in breast cancer. International (Ludwig) Breast Cancer Study Group.

PURPOSE: To evaluate the prognostic importance of immunocytochemically determined c-erbB-2 overexpression in the primary tumors of patients with breast cancer. PATIENTS AND METHODS: Primary tumors from 1,506 breast cancer patients (760 node-negative and 746 node-positive) who were treated in the International (Ludwig) Breast Cancer Study Group Trial V were studied. Node-negative patients were allocated randomly to either a single cycle of perioperative chemotherapy (PeCT) or no adjuvant treatment, and node-positive patients received either a prolonged chemotherapy (with tamoxifen for postmenopausal patients) or a single perioperative cycle. RESULTS: Tumors from 16% of the node-negative patients and 19% of the node-positive patients were found to be c-erbB-2-positive. In both groups c-erbB-2 positivity correlated with negative progesterone receptors (PR), negative estrogen receptors (ER), and high tumor grade. Lobular carcinomas were all negative, and, thus support the view that such tumors represent a defined subtype of breast carcinoma. The expression of c-erbB-2 was prognostically significant for node-positive but not for node-negative patients. However, in both subgroups, the prognostic significance was greater for patients who had received more adjuvant therapy. For node-positive patients, the effect of prolonged-duration therapy on disease-free survival (DFS) was greater for patients without c-erbB-2 overexpression (hazards ratio [HR], = 0.57; 95% confidence interval [CI], 0.46 to 0.72) than for those with c-erbB-2 overexpression (HR, 0.77; 95% CI, 0.51 to 1.16). Similarly, for node-negative patients, the effect of PeCT on DFS was greater for those without c-erbB-2 overexpression (HR, 0.82; 95% CI, 0.61 to 1.09) than for those with c-erbB-2 overexpression (HR, 1.22; 95% CI, 0.66 to 2.25). CONCLUSION: We conclude that tumors with overexpression of the c-erbB-2 oncogene are less responsive to cyclophosphamide, methotrexate, and fluorouracil (CMF)-containing adjuvant therapy regimens than those with a normal amount of gene product.

Adult↗
PubMed1992

[Ulcerated breast cancer of the young patient: a case report].

A 29-year-old woman presented with an exulcerating cancer of the right breast. She underwent a total mastectomy and axillary clearance which revealed a pathological stage of T4 N+ (21/23) M0. She received chemotherapy followed by radiation therapy and by chemotherapy again. 30 months later, a contralateral breast cancer was diagnosed. A close team-work of gynaecologist, plastic surgeon, medical and radiation oncologists allowed to combine the operation with the reconstruction of both breasts together with chemotherapy and irradiation of the left chest wall (the tumor was focally infiltrating the pectoralis muscle). We would like to show that a reconstruction of the breast in a young woman presenting with a bad prognosis can be carried out provided a well-organized team-work.

Adult↗
PubMed1992

Quality of life in clinical trials of adjuvant therapies. International Breast Cancer Study Group (formerly Ludwig Group).

Clinical trials of adjuvant therapies usually measure the effectiveness of treatments by comparing disease-free survival or overall survival. These take into consideration only indirectly the quality of life experienced by the patients. We present some approaches that were developed to assess the impact of adjuvant therapy on the quality of life of breast cancer patients, as well as new methods created to compare treatments based on time spent without symptoms and toxicity (TWiST). The integration of these two methods (measuring quality and comparing duration of time) will provide a new tool for evaluating benefits from treatments given in the adjuvant setting.

Antineoplastic Agents↗
PubMed1992

Reporting and interpreting adjuvant therapy clinical trials. International Breast Cancer Study Group (formerly Ludwig Group).

Identifying effective adjuvant treatments for patients with node-negative breast cancer is made difficult by the heterogeneity of the disease, the relatively low event rate and long follow-up time required, and the small magnitude of effects of current therapies. Several aspects of clinical trials that influence the appropriate reporting and interpretation of statistical results are discussed. We point out that the P value is a measure of the statistical uncertainty of an observed outcome and depends on the number of events available for analysis; it is not a measure of the magnitude of a treatment effect. We recommend that the relative reduction in the risk of an event and its 95% confidence interval be presented as an estimate of the treatment effect size, and that absolute improvements be used to judge whether treatment benefits outweigh the costs for the patient population. We suggest that subgroup analyses are important to define treatment effects within groups with different prognoses, and should be used with the understanding that multiple comparisons increase the chance of a false-positive result. Subgroup analysis should rely on the estimates of relative treatment effect and should avoid the use of the P value to declare incorrectly that "treatment is effective for one subgroup but not for another." We present the meta-analysis (overview) as a powerful method to demonstrate the statistical significance of a modest treatment effect by increasing the number of events available for analysis. The interpretation of overviews should consider the potential for treatment interactions and the validity of indirect comparisons that are not protected by a randomized design.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Neoplasms↗
PubMed1992

A single perioperative adjuvant chemotherapy course for node-negative breast cancer: five-year results of trial V. International Breast Cancer Study Group (formerly Ludwig Group).

Twelve hundred seventy-five patients who were defined as having node-negative breast cancer were evaluated in a randomized trial that compared a single cycle of combination chemotherapy started within 36 hours of surgery (848 patients) with no adjuvant treatment (427 patients). The chemotherapy consisted of intravenous cyclophosphamide, methotrexate, and fluorouracil given on days 1 and 8. Leucovorin (given on days 2 and 9) was added to the regimen to decrease severe toxic effects attributed to drug interaction between nitrous oxide used in anesthesia and methotrexate given in the immediate postoperative period. At a median follow-up of 60 months, the 5 year disease-free survival (DFS) percentages (+/- SE) were 74% +/- 2% for the treated group, and 68% +/- 2% for the no adjuvant therapy group. The estimated hazard ratio [95% confidence interval (CI)] was 0.78 (0.63 to 0.96); P = .02, representing a 22% +/- 9% relative reduction in the risk of relapse. The overall survival (OS) difference was not statistically significant with 5-year OS percentages of 88% +/- 1% for the treated group, and 85% +/- 2% for the control group [estimated hazard ratio (95% CI) = 0.85 (0.62 to 1.16); P = .31]. A subgroup analysis by menopausal status and by estrogen-receptor (ER) status revealed that the treatment effect was largest among the postmenopausal women with ER-negative tumors. The 5-year DFS percentages were 79% +/- 4% and 56% +/- 7%, and the OS percentages were 91% +/- 3% and 70% +/- 6%, for the treated and control groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
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

Continuous 5-day infusion of ifosfamide with mesna in inoperable pancreatic cancer patients: a phase II study.

Phase II studies on ifosfamide and mesna in pancreatic cancer have mostly been inconclusive. In all of these studies ifosfamide was administered as an i.v. bolus or by short infusions. Since dose fractionation of ifosfamide over several days increases its therapeutic index, we chose to maximize the dose fractioning by selecting a continuous-infusion schedule (1.75 g/m2 on days 1-5 every 21-28 days, with mesna 60%-100% of the ifosfamide dose up to 12 h after ifosfamide). Since 1987 29 patients (performance status less than or equal to 2) with advanced inoperable adenocarcinoma of the pancreas were studied (8 women and 21 men; median age 58 years: 36-73 years). A total of 25 patients are evaluable for response (1 ineligible; 3 inevaluable: 2 early deaths due to disseminated intravascular coagulation, 1 refusal). One female patient with a complete response on computed tomography scan (after five cycles) but residual liver metastases on surgical exploration survived for 473 days. Three male patients with partial response survived for 205, 335 and 355 days. Six more patients with minor response (3) or no change (3) but significant decrease of tumour marker CA 19-9 had a median survival of 213 days (106-243). Responders seemed to benefit in terms of pain relief and general well-being. The median overall survival of all patients was 148 days (21-473). Haematotoxicity was rarely dose-limiting [median nadirs: white blood cells = 2.1 x 10(9)/l (0.45-6.4), Hb = 10.7 g/dl (7.5-13), platelets = 137 x 10(9)/l (21-411)]. Nausea and vomiting were mild with prophylactic oral metoclopramide. No central nervous system toxicity or urotoxicity was observed. Alopecia was seen in all patients who had received at least two cycles. Continuous infusion of ifosfamide was generally well tolerated and useful for palliation in 10 of 25 patients. A higher dose intensity is recommended.

Adenocarcinoma↗
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

Phase I study of the combination of monthly carboplatin and weekly cisplatin.

Two cycles of the combination of carboplatin (C), given every 4 weeks with weekly doses of cisplatin (P), were administered on an outpatient basis to 28 previously untreated patients. One cycle consisted of one dose of C and 4 doses of P. The toxicity of 250 mg/m2 of C, combined with escalating doses of P (20, 30, 35, 40 mg/m2) was evaluated first. Thrombocytopenia was dose-limiting and cumulative. At the dose level of 40 mg/m2 of P, the median Pt nadirs during the first and second cycles were 190 (range: 44 to 232) x 10(3)/microL and 90 (range: 15 to 165) x 10(3)/microL, respectively. The median delivered dose intensity (DI) of P was 40 mg/m2/wk in the first cycle and 40 mg/m2/wk in the second cycle. In the second part of the study, 40 mg/m2 of P were combined with a C dose adapted to individual renal function according to the formula dose (mg) = AUC x (GFR + 25) where AUC = 4.5 mg/mL/min. The administration of doses of C ranging from 219 to 493 mg/m2 was associated with a more severe and more variable thrombocytopenia, more frequent P delays and decrease of the median delivered DI of P (first cycle: 33 mg/m2/wk; second cycle: 32 mg/m2/wk). At all dose levels, leukopenia was mild to moderate, and neurotoxicity and severe GI toxicity were absent. No significant reductions of the creatinine clearance values were observed. All patients treated at 40 mg/m2 of P suffered from cumulative subjective toxicity during the second month of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
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

[Adjuvant systemic therapy in breast carcinoma in the 1990s: status of things and open questions].

Adjuvant systemic therapy of breast cancer has been shown to reduce relapses and prolong survival in the women treated. This is true of all subpopulations studied. Six-month multidrug chemotherapy in premenopausal patients, and tamoxifen or short-term chemotherapy in postmenopausal patients, are the treatments of choice in reducing the risk of relapse. In the near future ongoing research may answer some of the open questions surrounding the definition of populations for which the risk of relapse justifies therapy and the optimum manner of using available therapies. The modest but real improvement in prognosis of operable breast cancer was obtained solely by means of clinical trials. Participation in clinical research programs is becoming medically and socially mandatory.

Adult↗