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Biomedical subjects

A Goldhirsch

Publications and source records attributed to A Goldhirsch.

321 records · Page 18Linked to original sources

[Unusual autoimmune and neoplastic associated diseases in Sjogren's syndrome].

In an unselected series of 12 patients with Sjögren's syndrome the following autoimmune diseases were observed: severe myxedema due to Hashimotos thyroiditis in four, subclinical thyroid hypofunction in one, diffuse hyperthyroidism in one, glomerulonephritis in two, chronic active hepatitis in one, lupus erythematodes disseminatus in three (one with idiopathic thrombocytopenic purpura), classical rheumatoid arthritis in two. A rare familial occurrence was seen in two sisters. The only male in this group exhibited coexistence of a benign adenolymphoma of the parotid gland (Warthin's tumor) with a malignant non-Hodgkin lymphoma.

Adult↗

[Preliminary results of a phase-II study with DDP (cis-diaminedichloro-platinum) in the small cell bronchogenic carcinoma].

Eleven patients with measurable, previously treated oat-cell carcinoma of the lung received DDP 80 mg/m2 once every three weeks. The drug was given as a 6-hour infusion. In 4 patients a partial remission was achieved: 2 others showed a minor tumor regression. The main toxicity was vomiting, whereas generally myelosuppression and nephrotoxicity were manageable. Based on these preliminary data, a further investigation of DDP in the treatment of oat-cell carcinoma of the lung is definitely warranted.

Carcinoma, Small Cell↗

[Prolymphocytic leukaemia: a new clinical entity (author's transl)].

A 67-year-old woman, at first diagnosed to have acute lymphocytic leukaemia, developed all the characteristic signs of so-called prolymphocytic leukaemia, namely severe general symptoms of illness, marked hepatosplenomegaly in the absence of lymphadenopathy, extreme leukocytosis (at times more than 1000 x 10(9)/l). Prolymphocytic leukaemia is now considered to be an especially unfavourable form of chronic lymphocytic leukaemia.

Aged↗

Interpretation of results from subset analyses within overviews of randomized clinical trials.

Evaluating treatment effects within different subsets of patients is a common practice in the analysis of individual randomized clinical trials. Such analyses are limited, however, by the number of patients available. Overviews, by providing evidence based on large numbers of patients, can be useful for overcoming the difficulties of detecting therapeutic effects within subsets of patients. However, inconsistent subset definitions, misclassification of patients, and incomplete availability of patient subsets from the trials included in the overview bias the estimates of effect size. Separate analyses of subsets of studies are also possible within an overview. Studies being pooled generally differ with respect to treatments applied, control groups, patient eligibility, quality control, study conduct, and follow-up maturity. Separate comparisons within subsets defined by these features will be misinterpreted unless confounding factors are recognized. Indirect comparisons between overviews have the same informative value as nonrandomized trials with historical controls.

Breast Neoplasms↗

Cisplatin and vinorelbine as second-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) resistant to taxol plus gemcitabine.

The aim of the study was to evaluate the activity of cisplatin (CDDP) plus vinorelbine (VNR) in patients with advanced non-small cell lung cancer (NSCLC) progressing after paclitaxel plus gemcitabine. Treatment consisted of CDDP 80 mg/m(2) administered on day 1 and VNR 25 mg/m(2) administered on day 1 and 8, repeated every 3 weeks. Nine patients who relapsed after partial response and eight patients refractory to prior CT received a minimum of two treatment cycles: three patients achieved a PR (18%; 95% CI: 4-43%), four had stable disease and 10 had disease progression. All responses were observed among the nine patients responsive to prior treatment. Median survival was 35 weeks. No patients required dose-reduction, treatment discontinuation or delay because of toxicity. Our results indicate a reasonable antitumor efficacy and no relevant toxicity of a second-line CDDP-based chemotherapy in patients with advanced NSCLC. We recommend the use of this regimen for patients not refractory to primary treatment.

Adult↗

Acute erythroleukemia following chemotherapy for Hodgkin's disease.

A case of erythroleukemia developing in a patient 6.5 years after therapy for Hodgkin's disease (HD) is described. The patient had chemotherapy alone for a stage III B lymphocyte-predominant HD. He received six cycles MOPP-induction therapy followed by a chlorambucil maintenance therapy with procarbazine and prednisone reinforcements. To our knowledge this is the first case of erythroleukemia following HD treated with chemotherapy alone.

Acute Disease↗

Diagnosis of T1 bladder transitional cell carcinoma by denaturing gradient gel electrophoresis urinalysis.

OBJECTIVE: The diagnosis and follow-up of patients with T1 bladder cancer relies invasive procedures. We developed a non-invasive method for detection of T1 bladder cancer based on a feasible non-radioactive molecular approach. MATERIALS AND METHODS: Urine DNA samples were collected from 24 patients with T1 transitional cell carcinoma (TCC) of the bladder and were processed by denaturing gradient gel electrophoresis (DGGE) analysis. Urine samples obtained from 10 individuals with no clinical evidence of genitourinary malignancy were used as controls. RESULTS: Ten patients out of 24 (41%) had p53 mutations in their tumor samples. Seven of these presented the same mutation in matched urine samples. The p53 mutation pattern found in urine was always identical to that identified in the primary tumor. Decision diagnostic criteria showed that molecular screening by DGGE of amplified DNA from urine sediment had 69.2 % sensitivity, 100% specificity, 95.8 % accuracy, 100% prediction of positive result and 95.4 % prediction of negative result, respectively. No p53 mutation was found in the urine from control subjects. CONCLUSION: DGGE analysis of urine samples could be a useful tool for the early detection of T1 bladder cancer or its recurrence, potentially leading to a reduction in the frequency of invasive procedures used for the management of this disease.

Aged↗

Chemotherapy with vinorelbine, cisplatin and continuous infusion of 5-fluorouracil in locally advanced breast cancer: a promising low-toxic regimen.

Primary chemotherapy for locally advanced breast cancer, usually an anthracycline-containing regimen, improves local disease control allowing for an initially inoperable tumour to be resected. The feasibility and efficacy of a regimen containing vinorelbine (V), cisplatin (P) and 5-fluorouracil (5-Fu) as continuous infusion (ViFuP regimen) for patients with locally advanced breast cancer were evaluated. Twenty-six patients with a T4 breast cancer presentation (eight also had synchronous distant metastases) were treated with V (20 mg total dose i.v. on day 1 and day 3), P (60 mg/m2 i.v. on day 1) and 5-Fu (200 mg/m2/d as continuous infusion) all given every 3 weeks for a maximum of 6 courses. Eleven patients had an inflammatory breast lesion, 4 had a T4a and 11 a T4b presentation. Among those with metastases, 6 had one site and 2 had two sites of disease. After chemotherapy all tumors except one became operable. Objective response was observed in 19 out of the 26 evaluable patients (73%; 95% CI: 52-88%): fourteen had a partial response (54%); 5 had a clinically complete response (19%) and 5 had complete pathological response (20%; 95% CI: 7-41%). Seven patients had stable disease (27%) while no disease progression under treatment occurred. Mild or moderate side-effects included neutropenia (G1-G2 in 58% and G3 in 31% of patients), anemia (G1 in 19%), nausea and/or vomiting (G1-G2 in 92% of patients), mucositis (G1-G2 in 23%), diarrhea (G1 in 19%), plantar-palmar erythema (G1 in 12%) and alopecia G1 in 27% of patients. We conclude that the ViFuP regimen is well-tolerated and its use results in a high response rate. Thus ViFuP may be considered a relevant alternative to more toxic regimens, with an acceptable response rate. Despite the lack of a formal demonstration of equal efficacy with more toxic regimens commonly applied in locally advanced breast cancer, testing new modalities or drugs might provide a more fruitful strategy for relevant therapeutic progress.

Adult↗

Vinorelbine-based chemotherapy in hormone-refractory prostate cancer.

BACKGROUND: No consensus exists regarding further therapy for the management of hormone-refractory prostate cancer. In this phase II study, the combination of Vinorelbine with 5-Fluorouracil and folinic acid (FLN regimen) was evaluated in patients with progressive or resistant disease after hormone therapy. PATIENTS AND METHODS: Thirty-four patients were treated with Vinorelbine at a dose of 20 mg/m2 intravenously (i.v.) on days 1 and 3, folinic acid (FA), 100 mg/m2 i.v. and 5-Fluorouracil (5-FU), 350 mg/m2 i.v. as a short infusion on days 1 to 3. The therapy was given in an out-patient setting, every 3 weeks. RESULTS: All of the 34 eligible patients were evaluable for toxicity and 30 for activity. A total of 127 cycles was administered (91% at full dose). Among thelS5 patients with measurable disease, four had a partial response (26.6%; C.I. 95%, 28.3% to 65.7%) and four achieved stable disease. In 14 patients (47%) a clinical benefit was documented. Six out of 15 patients with bone-only involvement had stable disease (40%). The median duration of stabilization and partial response was 16 weeks (range 4-24 weeks). The most common toxicity was hematological: Grade 4 (NCI-CTC scale) in five patients at re-cycle. Other toxicities were of low incidence and easy to manage. CONCLUSION: The encouraging results obtained with the FLN regimen in terms of clinical benefit and its predictable and manageable toxicity support the palliative role of this chemotherapeutic strategy in hormone-refractory prostate patients.

Adenocarcinoma↗

A phase II study of primary dose-dense sequential doxorubicin plus cyclophosphamide and docetaxel in cT4 breast cancer.

BACKGROUND: Dose-dense chemotherapy with anthracyclines and taxanes has improved either disease free survival or overall survival in high risk patients with early breast cancer. PATIENTS AND METHODS: The activity and safety of a dose-dense schedule (q14 days) of adriamycin 60 mg/sqm and cyclophosphamide 600 mg/sqm (AC) x 4 cycles followed by docetaxel 75 mg/sqm for 4 cycles with hematopoietic support in patients with stage IIIB breast cancer was explored. Patients with ER > or =10% tumors received concomitant endocrine therapy with 3-month triptorelin and letrozole. RESULTS: Fifteen patients with histologically proven cT4b (three patients) and cT4d (twelve patients) M0 breast cancer were enrolled. Median age was 48 years (range 25-66). Eight clinical responses including one pathological complete remission (pCR), three stable disease (including minor responses) and four progression of disease, one during AC and three during taxotere, were observed. Four patients had grade 3-4 non hematological toxicities and all except one discontinued treatment. CONCLUSION: Due to the high rate of progressive disease, this schedule should not represent a standard option in cT4 breast cancer.

Adult↗

Combination chemotherapy with VM-26, adriamycin bleomycin, and prednisone as a secondary treatment of malignant lymphoma.

Thirty-eight pretreated patients with Hodgkin's disease (HD) and malignant non-Hodgkin's lymphoma were given combination chemotherapy with VM-26, Adriamycin, bleomycin, and prednisone. Four of 15 evaluable patients with HD achieved a partial remission (PR), with a median duration of 8 months. Of 12 patients with diffuse poorly differentiated lymphocytic lymphoma, one achieved a complete remission (30+ months) and five achieved a PR (median, 6 months). One of three patients with histiocytic lymphoma had a PR of 1.5 months. There was one drug-related death. Five patients developed life-threatening hematologic toxicity. Two HD responders died of acute nonlymphocytic leukemia.

Adult↗

The best available adjuvant treatments are within the framework of clinical trials. The International Breast Cancer Study Group.

The International Breast Cancer Study Group (IBCSG, formerly the Ludwig Group) is currently conducting several trials to improve available adjuvant therapies for operable breast cancer. Within the framework of clinical trials, treatment is available for several subpopulations of patients with operable disease. Two trials for patients with node-negative breast cancer question the efficacy of the combination of chemotherapy and endocrine manipulation. Four trials for patients with node-positive disease investigate questions of chemoendocrine therapy and of delayed reintroduction of chemotherapy after an initial cytotoxic treatment. One trial for elderly patients investigates the role of axillary lymph node dissection in terms of treatment outcome and quality of life. The ongoing trials are based on the results of past investigations by the Group: seven clinical trials, conducted since 1978, tested hypotheses of timing, duration, and the combined use of chemo- and endocrine therapies. Several ancillary studies were conducted using the database amassed from these trials, including pathological findings in node-negative disease, significance of micrometastases detected by serial sectioning of axillary nodes, importance of c-erbB-2 oncogene expression for prediction of treatment responsiveness, patterns of relapse, and assessing the impact of adjuvant treatment for breast cancer on the patients' quality of life. This report presents updated results of the seven IBCSG trials conducted from 1978 to 1993 and describes the trials currently open to patient accrual.

Aged↗

Adjuvant chemotherapy for premenopausal breast cancer: a meta-analysis using quality-adjusted survival.

PURPOSE: Adjuvant chemotherapy for early breast cancer has been shown to offer an improvement in recurrence-free and overall survival, especially for younger women, but the acute toxic effects of this treatment discourage some physicians from prescribing it. The purpose of this analysis was to determine whether the benefit of 6 months of adjuvant CMF (cyclophosphamide, methotrexate, fluorouracil) treatment outweighs its costs in terms of toxic effects. METHODS: A meta-analysis of quality-adjusted survival was performed based on data from 1229 patients, aged 49 years or younger, randomized in eight trials comparing CMF versus no adjuvant systemic therapy. The eight trials were included in the worldwide overview conducted by the Early Breast Cancer Trialists' Collaborative Group. The Q-TWiST method was used in a meta-analysis that provided treatment comparisons incorporating differences in quality of life associated with the amount of time patients spend with subjective toxic effects, after relapse, and without symptoms of relapse. RESULTS: Within 6 years of follow-up evaluation for patients with node-positive disease, the benefit in terms of increased relapse-free and overall survival balanced the costs in terms of acute toxic side effects. This was true even for the extreme case in which a zero value was assigned to all 6 months during which patients might receive adjuvant CMF chemotherapy. Within 10 years of follow-up evaluation, treated patients gained an average of 1.5 years of relapse-free survival time, almost 1 year of overall survival time, and 1 year of time without symptoms and toxicity. CONCLUSIONS: Adjuvant chemotherapy for younger women with node-positive breast cancer provided substantial amounts of quality-adjusted survival time, even after accounting for costs associated with toxic effects of the treatment. The Q-TWiST method represents a valuable tool for comparing treatments because it incorporates patients' perceptions of their quality of life for therapeutic decision-making.

Antineoplastic Combined Chemotherapy Protocols↗