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Biomedical subjects

C Blomqvist

Publications and source records attributed to C Blomqvist.

At least 91 records · Page 5Linked to original sources
PubMed1996

Antiatherogenic effects of adjuvant antiestrogens: a randomized trial comparing the effects of tamoxifen and toremifene on plasma lipid levels in postmenopausal women with node-positive breast cancer.

PURPOSE: To evaluate whether a novel antiestrogen, toremifene, has similar antiatherogenic effects as tamoxifen. PATIENTS AND METHODS: Forty-nine postmenopausal patients with node-positive breast cancer were randomized in a trial that compared the effects of tamoxifen and toremifene on serum lipoproteins. Tamoxifen was given at 20 mg and toremifene at 60 mg orally per day for 3 years. Serum concentrations of apolipoprotein (apo) A-I, A-II, and B, and lipoprotein(a) [Lp(a)], cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol were measured before and after 12 months of antiestrogen therapy. RESULTS: Both antiestrogens significantly reduced serum total and LDL cholesterol and apo B levels. However, the response of HDL cholesterol to treatments was clearly different between the groups. Toremifene increased the HDL level by 14%, whereas tamoxifen decreased it by 5% (P = .001). As a consequence, both cholesterol-to-HDL and LDL-to-HDL ratios decreased more in the toremifene than tamoxifen group (P = .008 and P = .03, respectively). Toremifene also increased the apo A-I level (P = .00007) and apo A-I-to-A-II ratio (P = .018). Both tamoxifen and toremifene decreased the Lp(a) concentration significantly (change, 34% v 41%). CONCLUSION: These results provide positive evidence that toremifene has antiatherogenic properties with potency to improve all lipoproteins that are associated with increased coronary heart disease (CHD) risk.

Antineoplastic Agents, Hormonal↗
PubMed1996

Anastrozole, a potent and selective aromatase inhibitor, versus megestrol acetate in postmenopausal women with advanced breast cancer: results of overview analysis of two phase III trials. Arimidex Study Group.

PURPOSE: To compare the efficacy and tolerability of anastrozole (1 and 10 mg once daily), a selective, oral, nonsteroidal aromatase inhibitor, and megestrol acetate (40 mg four times daily), in postmenopausal women who progressed following tamoxifen treatment. PATIENTS AND METHODS: Two randomized, double-blind for anastrozole, open-label for megestrol acetate, parallel-group, multicenter trials were conducted in 764 patients. Because both trials were identical in design, an analysis of the combined results was performed to strengthen interpretation of results from each trial. RESULTS: The median follow-up duration was approximately 6 months. The estimated progression hazards ratios were 0.97 (97.5% confidence interval [CI], 0.75 to 1.24) for anastrozole 1 mg versus megestrol acetate and 0.92 (97.5% CI, 0.71 to 1.19) for anastrozole 10 mg versus megestrol acetate. The overall median time to progression was approximately 21 weeks. Approximately one third of patients in each group benefited from treatment. Twenty-seven patients (10.3%) in the anastrozole 1-mg group, 22 (8.9%) in the anastrozole 10-mg group, and 20 (7.9%) in the megestrol acetate group had a complete or partial response, and 66 (25.1%), 56 (22.6%), and 66 (26.1%) patients, respectively, had stable disease for > or = 24 weeks. For all end points, individual trial results were similar to the results of the combined analysis. Anastrozole and megestrol acetate were well tolerated. Gastrointestinal disturbance was more common among patients in the anastrozole groups than the megestrol acetate group; the difference between the anastrozole 10 mg and megestrol acetate groups was significant (P = .005). Significantly fewer patients in the anastrozole 1-mg (P < .0001) and 10-mg (P < .002) groups had weight gain than in the megestrol acetate group. More than 30% of megestrol acetate-treated patients had weight gain > or = 5%, and 10% of patients had weight gain > or = 10%. Patients who received megestrol acetate continued to gain weight over time. CONCLUSION: Anastrozole, 1 and 10 mg once daily, is well tolerated and as effective as megestrol acetate in the treatment of postmenopausal women with advanced breast cancer who progressed following tamoxifen treatment. Moreover, anastrozole therapy avoids the weight gain associated with megestrol acetate treatment.

Adult↗
PubMed1996

Effects of chemotherapy-induced castration on serum lipids and apoproteins in premenopausal women with node-positive breast cancer.

The purpose of this study was to determine the effect of adjuvant chemotherapy on serum lipids and lipoproteins in premenopausal nonmetastatic breast cancer patients. Fifty-nine premenopausal breast cancer patients were treated with adjuvant chemotherapy comprising cyclophosphamide, methotrexate, and 5-fluorouracil. Levels of serum FSH, LH, and estradiol; fasting plasma levels of total cholesterol, high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), triglyceride, and apolipoprotein A-I, A-II, and B levels; and lipoprotein(a) [Lp(a)] were measured before treatment and 12 months after the beginning of chemotherapy. The changes in serum lipids after chemotherapy correlated significantly to changes in menstruation. Total cholesterol, LDL, and HDL cholesterol levels increased significantly only in patients with chemotherapy-induced ovarian dysfunction. Changes in apo B paralleled those in LDL and apo A-I and A-II HDL cholesterol. The serum concentration of Lp(a) increased significantly only in patients who developed permanent amenorrhea. There were no significant changes in triglyceride levels. Chemotherapy per se has no effect on serum lipids unless associated with induction of ovarian dysfunction. Ovarian failure after chemotherapy has an unfavorable effect on serum total and LDL cholesterol, apo B, and Lp(a) levels, but a favorable effect on HDL cholesterol.

Adult↗
PubMed1996

Bisphosphonate therapy in metastatic breast cancer.

Five long-term controlled studies on the effect of supportive bisphosphonate treatment in metastatic breast cancer with bone metastases have been published. In two of the studies pamidronate was used and in three clodronate. According to these trials supportive bisphosphonate treatment in metastatic breast cancer diminishes the risk of malignant, pathological fractures and bone pain. In several of these trials a retarding effect on the progression of previous and new bone metastases could also be documented. One further large trial, hitherto published only in abstract form, indicates that the development of bone invasion can also be retarded by bisphosphonate treatment in patients with metastatic breast cancer without bone metastases.

Antineoplastic Agents↗
PubMed1996

Results of treatment in testicular nonseminoma.

Seventy-one testicular nonseminomatous germ cell tumours were treated in the Helsinki University Central Hospital between 1980 and 1990. Thirty-five (49%) were stage I, 16 (23%) stage II and 20 (28%) stage III tumours. The 5-year survival rates were 91%, 94% and 70%, respectively. Five of the eight patients relapsing in stage I had adverse histopathological risk factors in their tumours. In the retrospective evaluation two stage I patients had actually a higher stage. The good results in stage II were achieved with a routine combination of chemotherapy and retroperitoneal lymph node dissection. All five patients lost for stage III nonseminoma had risk factors for unfavourable prognosis: liver metastases or very high serum markers at diagnosis. The results presented here are considerably better than in the 1970s in this country and well comparable to results from countries where this malignancy is more common. Still some patients were lost. Co-operation in different fields of medicine is essential to find and treat optimally those with more aggressive disease and those who are cured with less strenuous treatment modalities.

Adolescent↗
PubMed1995

Reduced expression of proapoptotic gene BAX is associated with poor response rates to combination chemotherapy and shorter survival in women with metastatic breast adenocarcinoma.

Bax is a homologue of Bcl-2 that promotes apoptosis. Bax protein levels were assessed by immunohistochemical methods in primary tumors derived from 119 women with metastatic breast cancer. These patients had received combination chemotherapy either with a once a month dosage schedule or in 4 weekly divided doses. The BAX immunostaining results were retrospectively compared with overall survival, time to tumor progression (TTP), and response, as well as several laboratory markers. Normal breast epithelium and in situ carcinomas immunostained positively for Bax. Marked reductions in Bax immunostaining were observed in 40 (34%) of 119 evaluable tumors. Reduced Bax correlated with shorter overall survival (median, 8.1 versus 15.7 months; P = 0.04), faster TTP (median, 2.0 versus 6.3 months; P = 0.009), and failure to respond (complete response, partial responses; 6% versus 42%, P = 0.01) in the subgroup of patients who received divided dose therapy. Reduced Bax immunostaining was not significant in the monthly dose group. When the two groups were combined, however, reduced Bax was significantly correlated in univariate analysis with failure to respond (21 versus 43% achieving complete response or partial response; P = 0.02), faster TTP (median, 3.7 versus 9.0 months; P = 0.02), and shorter survival (median, 10.7 versus 17.1 months; P = 0.04). Bax immunostaining was not significantly correlated with tumor histology, S-phase fraction, aneuploidy, p53 HER2, or cathepsin D, but was positively associated with Bcl-2 (P = 0.005). In multivariate analysis (Bax, tumor grade, and treatment group), reduced Bax was strongly associated with faster TTP (P approximately equal to 0.009) and shorter survival (P approximately equal to 0.001). Although highly preliminary, the finding suggest that loss of Bax immunostaining represents a novel prognostic indicator of poor response to chemotherapy and shorter survival in women with metastatic breast cancer, and raise the possibility that the subgroup of women with Bax-negative tumors may benefit from more aggressive therapy.

Adenocarcinoma↗
PubMed1995

Oral trofosfamide: an active drug in the treatment of soft-tissue sarcoma.

A total of 23 patients with metastatic sarcomas were treated with continuous oral trofosfamide, an alkylating agent structurally related to cyclophosphamide and ifosfamide. In all, 12 of the patients were chemotherapy-naive. Doses were escalated every 3rd week until the development of leukopenia of WHO grade 2. The treatment was well tolerated and produced little subjective toxicity. Leukopenia was the dose-limiting toxicity. The daily dose that produced grade 2 leukopenia was 200-250 mg in 65% of the patients. Three patients responded, all of whom had been treated with trofosfamide as first-line treatment.

Administration, Oral↗
PubMed1995

A cytogenetic study of malignant fibrous histiocytoma.

We report the results of cytogenetic analysis of malignant fibrous histiocytoma of soft tissue (MFH). Seven of 12 successfully cultured MFHs had complex clonal aberrations, including translocations, deletions, and unidentifiable marker chromosomes. Telomeric associations were observed in five and the double minute phenomenon in four of seven MFHs with abnormal karyotypes. In one case (a storiform-pleomorphic MFH, grade IV) with a complex polyploid karyotype, two clonal ring chromosomes were present, one interpreted as r(19)(p13q13), one unidentified. In two tumors, clonal structural rearrangements of chromosome 1 were seen: del(1)(q21) in a storiform-pleomorphic MFH, grade IV, and add (1)(q21 or q32), t(1;10)(p22;q22) in a myxoid MFH, grade I. The remaining five MFHs had normal karyotypes, but in two of them nonclonal, structural aberrations were found. The modal chromosome number in the studied MFHs varied widely, but the majority of tumors with abnormal karyotypes had polyploid chromosome complements (five of seven cases). Our results confirm many of the previous findings and indicate that double minutes (dmins) may be more frequent in MFH than previously reported.

Adolescent↗
PubMed1995

Vinorelbine and epirubicin in metastatic breast cancer. A dose finding study.

The aim of the study was to define the maximum tolerated dose (MTD) of vinorelbine given as one or two weekly doses in combination with epirubicin 60 mg/m2 every third week. The MTD was defined as the dose resulting in a WHO grade III or IV leucopenia exceeding 50% of patients. Patients were treated in groups of 10 at escalating doses of vinorelbine. The number of patients at the final dose level was expanded to 20. The dose of epirubicin was kept constant at 60 mg/m2 every third week. At dose level 1, 15 mg/m2 vinorelbine was given on day 1 at level 2, 20 mg/m2 was given on day 1 and at level 3, 20 mg/m2 was given on days 1 and 8. The MTD was reached at dose level 3. WHO haematological toxicity grade IV occurred in 0, 10 and 45% and grade III at 60, 30 and 30% of patients at dose levels 1, 2 and 3, respectively. Despite the common occurrence of grade IV haematological toxicity, only two serious infections were noted. Non-haematological toxicity of vinorelbine included neurotoxicity, manifesting as muscle weakness, constipation and paresthesias in the majority of patients. Neurotoxicity was usually mild and did not require treatment discontinuation. Phlebitis at the injection site was troublesome in many patients. Alopecia and nausea, probably due to epirubicin, occurred in most patients. The response rates were 22% (95% CI (confidence interval) 3-60%), 40% (12-74%) and 60% (36-81%) at levels 1, 2 and 3, respectively (non-significant).

Aged↗
PubMed1995

The prognosis of stage III breast cancer treated with postoperative radiotherapy and adriamycin-based chemotherapy with and without tamoxifen. Eight year follow-up results of a randomized trial.

Sixty-one patients with primary node positive stage III breast cancers were randomized to receive postoperative radiotherapy and doxorubicin-based chemotherapy (eight cycles of CAFt: cyclophosphamide, adriamycin, oral ftorafur) with or without tamoxifen as adjuvant treatment. The five-year overall survival for all patients was 49% (with tamoxifen 48% and without tamoxifen 50%) and disease-free survival 33% (with tamoxifen 27% and without 39%). Local control for all patients was only 64% despite the postoperative radiotherapy. There was no significant difference between these two treatment groups in overall and disease-free survival or local control. The prognosis of stage III breast cancer remains grim despite modern adjuvant therapy. In addition to more effective systemic treatment more effective local therapy is also needed in order to obtain satisfactory local control. The most important studies in stage III breast cancer with 5-year survival results are reviewed here.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Do DNA ploidy and S-phase fraction in primary tumour predict the response to chemotherapy in metastatic breast cancer?

The relationship between the response to chemotherapy with cyclophosphamide, epirubicin and fluorouracil as well as the time to progression of metastasised breast cancer and DNA ploidy and S-phase fraction (SPF) of primary tumours was examined using paraffin-embedded tumour tissue from 81 patients. The response to chemotherapy was significantly better in patients with tumours with a high SPF, and in addition the time to progression was longer in the high-SPF group. There was no significant difference when the DNA ploidy and response to treatment were compared.

Adult↗
PubMed1995

Clodronate and other bisphosphonates as supportive therapy in osteolysis due to malignancy.

Clodronate, one of the most investigated bisphosphonates, has been clinically utilised for over 10 years in malignancy. It is the most used, most effective and safest drug in the treatment of hypercalcaemia. It inhibits lytic bone destruction, prevents bone fractures and relieves bone pain. Supportive clodronate therapy may even reduce hypercalcaemia mortality and the morbidity caused by osteolysis. These results have stimulated studies on the patients' quality of life. New methods for the measurement of bone resorption, such as the degradation product of type I collagen (ICTP), may improve the possibility of monitoring the effect of clodronate. Comparative studies with different bisphosphonates in hypercalcaemia and long-term controlled trials using bisphosphonates as supportive therapy in osteolysis due to malignancy are reviewed.

Clodronic Acid↗
PubMed1994

Salvage therapies in women who fail to respond to first-line treatment with fluorouracil, epirubicin, and cyclophosphamide for advanced breast cancer.

PURPOSE: We studied all salvage therapies given until death or the end of follow-up evaluation in women who failed to respond to the same first-line cytotoxic therapy for metastatic breast cancer. PATIENTS AND METHODS: The study cohort consisted of 140 women who had received the fluorouracil, epirubicin, and cyclophosphamide (FEC) regimen for metastatic breast cancer. Eight patients were excluded. No exclusions with respect to disease site, performance status, or biochemical abnormalities were made. The median follow-up time was 29 months for surviving patients. RESULTS: Most patients (88%) died during the follow-up period. Patients received a median of three salvage therapies (range, zero to eight) during the course of disease. Most courses (52%) were not assessable for response. Fifty-percent of courses consisted of chemotherapy: 35% of hormonal and 15% of combination of cytotoxic and hormonal therapies. The median duration of therapy (DT) ranged from 4 to 1 months, and decreased with advancing stages of therapy. Similarly, median time to treatment failure (TTF) ranged from 3 to 0.5 months. For unknown causes, patients who received second-line hormonal therapy fared better than those who received other forms of therapy. Of 366 analyzed courses, only one complete response (CR) and 18 partial responses (PRs) were observed (response rate, 11% for assessable and 5% for all courses). Stable disease for at least 3 months was found in 20% to 25% of courses. Most responses (n = 10) occurred during first salvage therapy, and no responses were observed after third salvage therapy. CONCLUSIONS: Response rates for salvage therapies were low, and median treatment times short. The value of offering more than two salvage chemotherapy regimens to an unselected group of patients is questionable.

Adult↗
PubMed1993

Comparative effects of clodronate and calcitonin on bone in metastatic breast cancer: a histomorphometric study.

We studied the effects of long-term treatment with clodronate, calcitonin or placebo on bone in 36 normocalcaemic women with osteolytic metastases due to breast cancer. Clodronate (1.6 g daily given to 12 patients) induced a significant decrease in osteoclast surface and osteoclast number, and a significant fall in serum calcium and urinary excretion of calcium and hydroxyproline, an effect not noted after treatment with calcitonin (100 U in 12 patients) or in 12 placebo-treated patients. Treatment with clodronate did not abnormally suppress bone turnover nor impair mineralisation, as measured by bone formation and mineral apposition rates.

Adult↗
PubMed1993

Measurement of growth rate of lung metastases in 21 patients with bone or soft-tissue sarcoma.

The volume doubling time (T2) of 52 lung metastases in 21 patients was calculated from measurements done on plain chest radiographs. Follow-up times ranged from 14 to 819 days. The measurements were fairly well reproducible in the majority of patients, although considerable discrepancies in T2 estimates made by two independent observers were found in a few patients. The median doubling time was 34.9 days (estimated 95% range 3.9 to 352 days). The variation of T2:s between patients was significantly (P = 0.0001) larger than that between T2: of multiple metastases in the same patients. The growth of the metastases seemed to be well described by a simple exponential function in all patients with more than two measurements, without evidence of Gompertzian growth. There seemed to be a linear correlation between the logarithm of T2 and log-survival time from diagnosis of metastatic disease, even if only one third of the variation of survival times between patients could be explained by differences in T2. T2 was not a significant factor for survival in Cox-analysis (P = 0.10).

Adult↗
PubMed1993

Influence of treatment schedule on toxicity and efficacy of cyclophosphamide, epirubicin, and fluorouracil in metastatic breast cancer: a randomized trial comparing weekly and every-4-week administration.

PURPOSE: To compare the effect on toxicity and efficacy of the fluorouracil 500 mg/m2, epirubicin 60 mg/m2, and cyclophosphamide 500 mg/m2 (FEC) regimen divided into 4 weekly doses with conventional every-4-week administration in metastatic breast cancer. PATIENTS AND METHODS: The inclusion criteria demanded measurable or assessable metastases from breast cancer and a World Health Organization (WHO) performance index of 2 or less. One hundred seventy-three patients with metastatic breast cancer who had not been treated with anthracyclines were randomized to receive FEC once every 4 weeks or once a week. The scheduled monthly doses of the cytotoxic agents were identical in both groups. Three patients were excluded from analysis. RESULTS: Hematologic toxicity, alopecia, nausea, and vomiting were significantly more severe in the group that received treatment every 4 weeks. The response rate was higher in the group that received FEC every 4 weeks than in the group treated weekly (47% v 30%, P = .02). Time to progression was significantly (P = .005) longer with every-4-week FEC treatment (median, 9.2 months v 5.4 months for weekly treatment). Patients in the group treated every 4 weeks lived significantly (P = .01) longer than patients treated weekly (median survival times, 21.2 months v 11.8 months, respectively). The actually delivered monthly dose levels and treatment duration were similar in the two groups. CONCLUSION: Both efficacy and toxicity of FEC were greater when treatment was administered every 4 weeks rather than once a week, despite identical dose intensity.

Adult↗