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Biomedical subjects

Jonas Bergh

Publications and source records attributed to Jonas Bergh.

48 records · Page 3Linked to original sources
PubMed2003

Quality of life in women with breast cancer during the first year after random assignment to adjuvant treatment with marrow-supported high-dose chemotherapy with cyclophosphamide, thiotepa, and carboplatin or tailored therapy with Fluorouracil, epirubicin, and cyclophosphamide: Scandinavian Breast Group Study 9401.

PURPOSE: To compare, in high-risk breast cancer patients, the effects on health-related quality of life (HRQoL) of two adjuvant treatments. Treatments were compared at eight points during the first year after random assignment to treatment with tailored fluorouracil, epirubicin, and cyclophosphamide (FEC) therapy for nine courses versus induction FEC therapy for three courses followed by high-dose chemotherapy with cyclophosphamide, thiotepa, and carboplatin (CTCb) supported by peripheral-blood stem cells. PATIENTS AND METHODS: From March 1994 to March 1998, 525 breast cancer patients (estimated relapse risk > 70% within 5 years with standard therapy) were included in the Scandinavian Breast Group 9401 study. HRQoL evaluation, using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30 and EORTC Breast Cancer Module-23, included 408 of 446 eligible patients in Finland, Norway, and Sweden. RESULTS: Eighty-four percent to 95% of the patients completed questionnaires at eight points of assessment. Nostatistically significant overall differences were found between the tailored FEC group and the CTCb group for any of the HRQoL variables. Statistically significant differences over time were found for all HRQoL variables. HRQoL in the CTCb group demonstrated a steeper decrease, but a faster recovery than in the tailored FEC group. Emotional functioning improved with increased time from randomization. Higher levels of problems in body image and arm symptoms were reported in the tailored FEC group compared with the CTCb group. Sexual functioning and satisfaction were impaired during the study period. CONCLUSION: Both treatments had a negative influence on HRQoL during the treatment period. Despite the aggressive therapies, the patient's HRQoL returned to levels found at inclusion on most variables.

Adult↗
PubMed2003

Best use of adjuvant systemic therapies II, chemotherapy aspects: dose of chemotherapy-cytotoxicity, duration and responsiveness.

The overall survival improvement by adjuvant chemotherapy is partly related to patient age, stage and chemotherapy regimens used. Too low dose dose-intensities or total doses will result in inferior outcomes. Conventional dose escalations above standard doses will not be beneficial for doxorubicin or cyclophosphamide, while an epirubicin dose of 90-100mg/m2 given every third week in polychemotherapy regimens results in overall survival gains. The issue is more complex, while retrospective analysis of adjuvant regimens have revealed inferior outcomes for patients receiving standard chemotherapy doses and regimens without toxicity. Most cytostatics demonstrate a marked inter-individual variation in different pharmacokinectic parameters, not compensated for by dosage based on body surface area. These facts have partly been the basis for the randomised Scandinavian Breast Group (SBG) studies SBG 9401 and 2000-1, respectively, using tailored dosage strategies aiming at interpatient equivalent dosage. Randomised studies using marrow supported-high dose strategies have so far not been demonstrated to result in overall survival improvements. G-CSF (granulocyte-colony stimulating factor) and dose-dense paclitaxel containing regimens have resulted in a small but significant survival gain compared with conventional three weekly regimens, challenging the present dogma of conventional three-four weekly scheduling, based on normal tissue side-effects rather than tumour biological considerations. The recent microarray based studies demonstrated marked inter-patient variability in gene expression and underline the potential for better patient selection and more tailored therapy strategies.

Anthracyclines↗
PubMed2003

Attainment and importance of life values among patients with primary breast cancer.

The main aims of this study were to investigate the extent to which women with recently diagnosed primary breast cancer (N = 29) and matched control subjects without cancer (N = 29) differ in perceived attainment and importance of life values and to study prospectively life value ratings during 1 year in a large group of recent attendees at mammography screening (N = 706). Life values were assessed by a study-specific version of a life value questionnaire, including ratings of the perceived attainment and importance of seven life value dimensions. Women with a recent diagnosis of primary breast cancer were found to attribute significantly more importance to positive relations than healthy controls. No other differences between these groups were found regarding the attainment or importance of life values. Perceptions of life values were found to vary as a function of age, marital or cohabitation status, and parenthood, and to be stable over a 9-month period in screening attendees. The implications of the current findings for the understanding of women's psychological adaptation to breast cancer are discussed.

Adaptation, Psychological↗
PubMed2003

Doxorubicin-resistant, MRP1-expressing U-1285 cells are sensitive to idarubicin.

A doxorubicin-resistant subline (U-1285dox(900)) was derived from the human small cell lung carcinoma cell line U-1285. U-1285dox(900) was exposed to a wide range of anticancer agents to determine its resistance profile. In contrast to U-1285 cells, the resistant subline U-1285dox(900) expressed elevated MRP1 mRNA detected by reversed transcriptase-polymerase chain reaction (RT-PCR) and MRP1 protein analyzed with Western blot. Neither MDR1 mRNA nor P-glycoprotein could be detected in the parental cell line or resistant subline. U-1285dox(900) exhibited high resistance to doxorubicin, epirubicin, daunorubicin, and vincristine, an intermediate resistance to mitoxantrone, and a low resistance to etoposide. A collateral sensitivity to cytosine arabinoside, chlorodeoxyadenosine, and melphalan was observed. The resistance could be reversed by buthionine-sulphoximine and verapamil for all tested drugs. Compared with daunorubicin, resistance to idarubicin was very low, 14-fold and 2.6-fold, respectively. This was associated with a higher accumulation due to a slower transport of idarubicin out of U-1285dox(900) cells.

Area Under Curve↗
PubMed2003

Prognostic correlation of basic fibroblast growth factor and vascular endothelial growth factor in 1307 primary breast cancers.

This study was designed to investigate the possible relationship between the protein expression of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) with p53 status, breast cancer prognostic factors, metastatic site, and survival after adjuvant therapy. Basic fibroblast growth factor and VEGF expression were determined by enzyme-linked immunosorbent assays in cytosol specimens obtained from 1307 patients with T1-3 primary breast cancer (789 node-negative, 518 node-positive) diagnosed between 1990 and 1997. The median follow-up time was 70 months. Increased bFGF expression was more frequently found in tumors with low VEGF expression (r = -0.286; P = 0.095). Increased bFGF was associated with smaller tumors (P < 0.001), absence of axillary metastasis (P = 0.003), low S-phase fraction (P < 0.001), and longer recurrence-free survival (RFS; P = 0.0038) and overall survival (OS; P = 0.0316). Vascular endothelial growth factor was a prognostic factor for RFS (P < 0.0001) and OS (P < 0.0001) in univariate and multivariate analyses (RFS: 95% CI, 1.1-1.7; P = 0.036; OS: 95% CI, 1.2-2.2; P = 0.002), whereas bFGF expression was not correlated with RFS or OS. Increased VEGF content was correlated with shorter survival after adjuvant endocrine therapy (RFS, P = 0.0004; OS, P = 0.0009). Patients with estrogen receptor-negative disease were excluded from the analysis. Basic fibroblast growth factor was not a prognostic factor after adjuvant systemic therapy, nor was it related to metastatic site. Expression of VEGF is an independent prognostic factor for patients with primary breast cancer. High bFGF expression was related to good prognostic features and longer survival times, but did not add prognostic information in multivariate analysis. The results might implicate that different angiogenic pathways exist in human breast cancer.

Breast Neoplasms↗
PubMed2002

Pulmonary toxicity after radiotherapy in primary breast cancer patients: results from a randomized chemotherapy study.

PURPOSE: Pulmonary toxicity was prospectively evaluated within a randomized trial for breast cancer patients at high risk for relapse, who postoperatively received as adjuvant therapy either 9 cycles of tailored chemotherapy (20 patients) (cyclophosphamide, epirubicin, 5-fluorouracil [FEC]) or standard FEC x 3 followed by high-dose chemotherapy (cyclophosphamide, thiotepa, carboplatin [CTCb]) supported by peripheral blood stem cell transplantation (14 patients). After high-dose chemotherapy or tailored FEC, all patients received locoregional radiotherapy (50 Gy/5 weeks), plus tamoxifen for 5 years. METHODS AND MATERIALS: Lung function tests (FVC, FEV1, and DL(CO)) were performed before chemotherapy and 9 months after radiotherapy. Computed tomography of the lungs was performed before radiotherapy and 6 weeks, 3 months, and 9 months after radiotherapy. RESULTS: Clinical signs of suspected pneumonitis were noted in 29% of patients, but only 1 patient needed symptomatic therapy. Radiologic changes were detected in 68% of patients, and they were most frequent at 3 months after radiotherapy. FVC decreased in both groups (tailored FEC: mean difference, -6.5%, p = 0.0005; CTCb: -2.0%, p = 0.21; tailored FEC vs. CTCb: -4.5%, p = 0.05). DL(CO) decreased significantly in both groups (tailored FEC: mean difference, -11.2%, p < 0.0001; CTCb: -5.6%, p = 0.02; tailored FEC vs. CTCb: -5.6%, p = 0.07). FEV1 decreased by 7.3% in patients treated with tailored FEC (p < 0.0001) and by 2.5% in patients treated with CTCb (p = 0.03) (tailored FEC vs. CTCb: 3.7%, p = 0.08). CONCLUSIONS: Changes in pulmonary function were thus detected in both groups, although to a greater extent in the tailored FEC group. The clinical significance of these findings should be balanced carefully against the improved, statistically significant relapse-free survival achieved with the tailored FEC regimen compared to high-dose CTCb + peripheral blood stem cell transplantation (PSCT).

Adult↗
PubMed2002

Life values before versus after a breast cancer diagnosis.

The main aim of this study was to investigate whether women's life values change with a breast cancer diagnosis. In addition, associations between life values and anxiety/depression ratings were investigated. Life value changes were prospectively studied in 517 women recalled for further examination after attending mammographic screening, 38 of whom were diagnosed with primary breast cancer. Life values were assessed by a study-specific version of a life value questionnaire, including ratings of the perceived attainment and importance of seven life value dimensions. Three months after being recalled, women diagnosed with primary breast cancer reported a reduction of the attainment and the importance of Health. In addition, these women reported changes in the perceived importance of Responsibility and Involvement. High levels of anxiety and depression in particular were associated with large discrepancies between attainment and importance for some life values. This suggests that changes in the perceived importance of some life values may constitute one part of women's psychological adaptation to a breast cancer diagnosis.

Adaptation, Psychological↗
PubMed2002

A population-based study on the first forty-eight breast cancer patients receiving trastuzumab (Herceptin) on a named patient basis in Sweden.

Several studies have presented data on the efficacy and tolerability of trastuzumab within clinical trials. As a minority of patients is included in these trials, we undertook this retrospective study to describe trastuzumab therapy in clinical routine and its tolerability. We reviewed the medical records of the first 48 patients in Sweden who received treatment with trastuzumab on a named patient basis with (n = 29) and without (n = 19) chemotherapy. Forty-six patients had metastatic disease and had failed to respond to several prior regimens before starting antibody treatment. Two patients had locally advanced breast cancer failing on given neoadjuvant therapy. Patients with breast cancers with strong (3+) c-erbB-2 overexpression tended to have an improved survival from start of trastuzumab treatment versus those with a moderate (2+) overexpression (p = 0.09). Adverse events were registered in 22 patients (46%). The most common and acute side effects were fever and chills (7 patients, 15%). The toxicity seemed reasonable but two patients (4%) suffered serious cardiac events, both of them having received previous treatment with antracyclines.

Antibodies, Monoclonal↗
PubMed2002

A novel B-cell line (U-2932) established from a patient with diffuse large B-cell lymphoma following Hodgkin lymphoma.

Little is known about mechanisms leading to secondary non-Hodgkin lymphomas (NHL) in patients treated for Hodgkin lymphoma (HL). Our aim was to characterise in detail a cell line derived from a diffuse large B-cell lymphoma (DLBCL) that had developed in a patient with relapsing HL. The cell line U-2932 was established from ascites in a patient suffering from DLBCL previously treated for HL with multiple chemotherapy regimens. Characterisation was based on morphology, immunophenotype, Epstein-Barr virus (EBV)-status, IgH gene rearrangement status, tumourigenicity, p53 sequencing, and immunohistochemical expression of p53, BCL-2 and BCL-6. The karyotype was investigated using G-banding, comparative genomic hybridisation (CGH) and spectral karyotype (SKY) analysis. This cell line shows typical morphological features of a DLBCL and grows as colonies in nude mice. It expresses a B-cell phenotype with a somatically hypermutated V(H)4-39 gene and is negative for EBV. The origin of U-2932 was confirmed by demonstrating an identical V(H)4 rearrangement in ascites from the patient. A point mutation of the tumour-suppressor gene p53 was detected in amino acid position 176 and immunohistochemical over-expression of the p53 protein was also demonstrated. U-2932 carries a complex karyotype including high-level amplifications of the chromosomal bands 18q21 and 3q27 and expresses aberrant BCL-2 and BCL-6 immunohistochemically. We were unable to investigate the clonal relationship between the original HL and U-2932. In conclusion, U-2932 is a unique B cell line established from a patient suffering from HL followed by NHL. Overexpression of BCL-2, BCL-6 and p53 may play a role in the tumourigenesis and drug resistance. This cell line may become a useful tool to better understand the mechanisms responsible for development of secondary NHL in patients treated for HL.

Adult↗
PubMed2002

Selection of chemotherapy by ex vivo assessment of tumor sensitivity to cytotoxic drugs: results of a clinical trial.

The feasibility of tumor sampling followed by ex vivo assessment of drug sensitivity, using the short-term fluorometric microculture cytotoxicty assay (FMCA), for selection of chemotherapy was investigated prospectively in patients with advanced cancer not amenable to standard treatment. Taxol (175 mg/m2 every 3 wk) was given to patients with tumor samples being low drug resistant (LDR) to Taxol ex vivo, to patients with no LDR drug, and if other drugs were unsuitable. The remaining patients received the most optimal drug(s) based on the FMCA results. Gastrointestinal cancer was dominating among the 61 eligible patients. Tumor sampling was safely performed in 75% by ultrasound-guided core biopsy. Eighty-two percent of the patients had Taxol. Five patients (8%) had a partial remission and 18 (30%) had stable disease. Tumor response was poorly predicted, probably because the Taxol excipient Cremophor EL is cytotoxic exclusively ex vivo. However, patients with tumor cells being LDR to at least one drug ex vivo lived significantly longer than those with no such drug.

Adolescent↗
PubMed2002

A Phase I study of CHS 828 in patients with solid tumor malignancy.

CHS 828 is a cyanoguanidine, which has demonstrated potent antitumor activity in preclinical tumor models. The activity of CHS 828 in vitro showed only low to moderate correlation to other antineoplastic agents suggesting a unique mechanism of action. Ten females and 6 males (median age 58 years) with solid tumors refractory to standard therapy were included in this Phase I study. The study drug was administered to fasting patients as a single oral dose on days 1-5 of each treatment cycle. Patients received one to six cycles of treatment. The doses ranged from 30 mg to 200 mg (total dose within a cycle). Hematological toxicity was generally mild and dominated by transient thrombocytopenia and lymphocytopenia. Nonhematological toxicity most frequently consisted of nausea, vomiting, diarrhea, fatigue, and localized genital mucositis. The dose-limiting toxicities were thrombocytopenia, thrombosis, esophagitis, diarrhea, and constipation. The recommended Phase II dose of CHS 828 was 20 mg once daily for 5 days in cycles of 28 days duration. The extent of systemic exposure of CHS 828 across patients was approximately dose proportional. The time at which the highest drug concentration occurs was 2.2 +/- 1.3 h and half-life was 2.1 +/- 0.52 h (mean +/- SD). Large intra- and interindividual variation in dose level-adjusted maximum plasma concentration and the area under the curve from time 0 h to infinity were observed. There was an apparent inverse relationship between systemic exposure of CHS 828, and thrombocyte and lymphocyte nadir levels. No objective tumor responses were observed, and 7 patients showed stable disease after two courses of therapy.

Administration, Oral↗