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Biomedical subjects

J W Nortier

Publications and source records attributed to J W Nortier.

At least 19 recordsLinked to original sources
PubMed2004

[A patient with an extremely severe immunohaemolytic anemia due to diclofenac].

A 77-year-old male was diagnosed with immunohaemolytic anaemia. He presented with fever, jaundice and oliguric renal insufficiency. He had been taking diclofenac for three days. Additional examinations and tests revealed a Coombs-positive haemolytic anaemia and thrombopenia. The micro-card gel-agglutination test demonstrated antibodies against diclofenac metabolites. After discontinuation of diclofenac and short-term treatment with prednisone and haemodialysis for two days, the patient made an almost full recovery. Haemolytic anaemia caused by diclofenac is rare. It can be caused by autoantibodies against erythrocytes and complement-fixing antibodies that bind to erythrocytes only in the presence of diclofenac or its metabolites. A timely diagnosis-supported by the appropriate laboratory tests--is of critical importance in this rare but extremely serious complication of the use of diclofenac. The treatment consists of withdrawal of diclofenac and supportive measures, possibly in combination with immunosuppressants.

Aged↗
PubMed2001

Effects of epoetin alfa on hematologic parameters and quality of life in cancer patients receiving nonplatinum chemotherapy: results of a randomized, double-blind, placebo-controlled trial.

PURPOSE: This randomized, double-blind, placebo-controlled clinical trial assessed the effects of epoetin alfa on transfusion requirements, hematopoietic parameters, quality of life (QOL), and safety in anemic cancer patients receiving nonplatinum chemotherapy. The study also explored a possible relationship between increased hemoglobin and survival. PATIENTS AND METHODS: Three hundred seventy-five patients with solid or nonmyeloid hematologic malignancies and hemoglobin levels < or = 10.5 g/dL, or greater than 10.5 g/dL but < or = 12.0 g/dL after a hemoglobin decrease of > or = 1.5 g/dL per cycle since starting chemotherapy, were randomized 2:1 to epoetin alfa 150 to 300 IU/kg (n = 251) or placebo (n = 124) three times per week subcutaneously for 12 to 24 weeks. The primary end point was proportion of patients transfused; secondary end points were change in hemoglobin and QOL. The protocol was amended before unblinding to prospectively collect and assess survival data 12 months after the last patient completed the study. RESULTS: Epoetin alfa, compared with placebo, significantly decreased transfusion requirements (P =.0057) and increased hemoglobin (P <.001). Improvement of all primary cancer- and anemia-specific QOL domains, including energy level, ability to do daily activities, and fatigue, was significantly (P <.01) greater for epoetin alfa versus placebo patients. Although the study was not powered for survival as an end point, Kaplan-Meier estimates showed a trend in overall survival favoring epoetin alfa (P =.13, log-rank test), and Cox regression analysis showed an estimated hazards ratio of 1.309 (P =.052) favoring epoetin alfa. Adverse events were comparable between groups. CONCLUSION: Epoetin alfa safely and effectively ameliorates anemia and significantly improves QOL in cancer patients receiving nonplatinum chemotherapy. Encouraging results regarding increased survival warrant another trial designed to confirm these findings.

Activities of Daily Living↗
PubMed2001

Aromatase and COX-2 expression in human breast cancers.

We have investigated aromatase and the inducible cyclooxygenase COX-2 expression using immunocytochemistry in tumors of a series of patients with advanced breast cancer treated with aromatase inhibitors. Aromatase was expressed in 58/102 breast cancers. This is similar to the percentage previously reported for aromatase activity. Interestingly, aromatase was expressed in a variety of cell types, including tumor, stromal, adipose, and endothelial cells. Since prostaglandin E2 is known to regulate aromatase gene expression and is the product of COX-2, an enzyme frequently overexpressed in tumors, immunocytochemistry was performed on the tissue sections using a polyclonal antibody to COX-2. Aromatase was strongly correlated (P<0.001) with COX-2 expression. These results suggest that PGE2 produced by COX-2 in the tumor may be important in stimulating estrogen synthesis in the tumor and surrounding tissue. No correlation was observed between aromatase or COX-2 expression and the response of the patients to aromatase inhibitor treatment. However, only 13 patients responded. Nine of these patients were aromatase positive. Although similar to responses in other studies, this low response rate to second line treatment suggests that tumors of most patients were no longer sensitive to the effects of estrogen. Recent clinical studies suggest that greater responses occur when aromatase inhibitors are used as first line treatment. In the intratumoral aromatase mouse model, expression of aromatase in tumors is highly correlated with increased tumor growth. First line treatment with letrozole was effective in all animals treated and was more effective than tamoxifen in suppressing tumor growth. Letrozole was also effective in tumors failing to respond to tamoxifen, consistent with clinical findings. In addition, the duration of response was significantly longer with the aromatase inhibitor than with tamoxifen, suggesting that aromatase inhibitors may offer better control of tumor growth than this antiestrogen.

Adipocytes↗
PubMed2001

Importance of local aromatase activity in hormone-dependent breast cancer: a review.

The cytochrome P-450 enzyme complex aromatase is the rate-limiting step in the production of oestrogens. It catalyses the conversion of androgens to oestrogens. In the treatment of hormone-dependent breast cancer in postmenopausal women, aromatase is the target for treatment with aromatase inhibitors. Recently registered aromatase inhibitors like anastrozole, letrozole and exemestane have proven to be effective therapy for advanced breast cancer in postmenopausal patients failing to respond to treatment with tamoxifen. Intratumoural aromatase activity has predictive value for response to treatment with aromatase inhibitors. Attempts are being made to find an immunohistochemical technique to determine aromatase in tumour tissue, which may serve as a predictive factor. In situ oestrogen synthesis through local aromatase activity in the tumour and adjacent tissue is probably a very important growth-stimulating system in hormone-dependent breast cancer. This synthesis can be blocked with aromatase inhibitors. The regulation of aromatase activity and the cell types that contribute to this process are the subject of extensive research. There seems to be a complex interaction between malignant cells and adjacent cells in which factors such as IL-6 and its soluble receptor, TNF-alpha and prostaglandin E2 play an important role in stimulating aromatase activity.

Journal Article↗
PubMed2000

[Adjuvant systemic therapy for patients with resectable breast cancer: guideline from the Dutch National Breast Cancer Platform and the Dutch Society for Medical Oncology].

There is an abundance of evidence that adjuvant systemic therapy with chemotherapy or endocrine therapy results in better survival for all patients with resectable breast cancer. The absolute 10-year survival advantage however varies for the different patient groups. Therefore, for each individual patient the choice of adjuvant therapy must take into account the potential benefits and the possible side effects. A group of medical oncologists from the Dutch National Breast Cancer Platform (NABON) and the Dutch Society for Medical Oncology (NVMO) prepared a guideline for the treatment of patients with early resectable breast cancer. The criterium for choosing adjuvant systemic therapy for the individual patient is an expected increase in 10-year survival of 5% or more. In the guideline a difference is made between patients with and without axillary lymph node metastasis. In patients with axillary lymph node metastasis the choice for adjuvant systemic therapy depends on the following prognostic factors: menopausal status, age, and the presence of estrogen and progesterone receptors in the tumour. In patients without axillary lymph node metastasis the choice depends also on the following prognostic factors: the size of the tumour, the mitotic activity index, or the histopathologic grade of differentiation.

Adult↗
PubMed2000

Extrapulmonary small-cell carcinoma: report of three cases and update of therapy and prognosis.

Three male patients with extrapulmonary small-cell carcinoma originating from esophagus, pancreas and prostate are described. The patient with the esophagus tumor had a combined small-cell and undifferentiated carcinoma. The other two patients had a pure small-cell carcinoma. All patients were treated with primary combination chemotherapy consisting of etoposide and cisplatin followed in one patient by locoregional radiotherapy. The patients with the esophagus and the pancreas tumor showed a partial response; the patient with the prostate tumor achieved a complete remission but relapsed with brain metastasis. All patients are alive 7, 13 and 19 months, respectively after initiation of the therapy. As in pulmonary small-cell carcinoma, primary chemotherapy is the treatment of choice in extrapulmonary small-cell carcinoma.

Aged↗
PubMed2000

Randomized phase II study of FEC day 1 + 8 and FEC day 1 in patients with advanced breast cancer.

BACKGROUND: Dose-intensive chemotherapy regimens without stem cell support have not resulted in an improved survival compared to standard dose regimens in patients with metastatic breast cancer. Combinations of an anthracycline, cyclophosphamide and 5 fluorouracil are still standard in such patients. The aim of this study was to investigate the two different schedules of epirubicin in a standard dose FEC regimen with respect to response and toxicity. MATERIALS AND METHODS: Patients were randomly assigned to receive a day 1 + 8 schedule (5FU and CTX 500mg/m2 day 1, epirubicin 40 mg/m2 day 1 and 8) or a day 1 schedule (5FU, CTX 500 mg/m2 and epirubicin 80 mg/m2 day 1), q day 21, both given without hematopoietic growth factors. A total of 104 eligible patients were analyzed, 52 in each arm. RESULTS AND CONCLUSIONS: A significantly higher relative dose-intensity was found for the day 1 schedule compared to the day 1 + 8 schedule. Although the trial was not set up to reliably detect a difference in response rate, this difference in relative dose-intensity in favour of the day 1 schedule does not suggest any improvement in response rate or duration of response for the day 1 schedule. Myelosuppression was severe in the day 1 + 8 schedule. We conclude that a day 1 + 8 FEC schedule has no advantage over a day 1 FEC schedule without hematopoietic growth factors in patients with metastatic breast cancer.

Adult↗
PubMed2000

Dose-dense epirubicin and paclitaxel with G-CSF: a study of decreasing intervals in metastatic breast cancer.

Anthracyclines and taxanes are very effective drugs in the treatment of advanced breast cancer. With G-CSF support, the dose-intensity of this combination can be increased by reducing the interval between chemotherapy cycles, the so-called 'shortening of cycle time'. We treated 36 patients with advanced breast cancer in a multicentre phase I/II study. The treatment regimen consisted of epirubicin 75 mg m(-2) followed by paclitaxel 135 mg m(-2) (3 h) in combination with G-CSF. At least six patients were treated in each cohort and were evaluated over the first three cycles. Starting at an interval of 14 days, in subsequent cohorts of patients the interval could be shortened to 10 days. An 8-day interval was not feasible due mainly to incomplete neutrophil recovery at the day of the next scheduled cycle. In the 10-day interval cohort it was feasible to increase the paclitaxel dose to 175 mg m(-2). The haematological and non-haematological toxicity was relatively mild. No cumulative myelosuppression was observed over at least three consecutive cycles. In combination with G-CSF, epirubicin 75 mg m(-2) and paclitaxel 175 mg m(-2) could be safely administered every 10 days over at least three cycles, enabling a dose intensity of 52 and 122 mg m(-2) per week, respectively.

Adolescent↗
PubMed1999

[Fever due to antithyroid agents].

Three patients, females aged 62, 67 and 32 years, were presented with fever and sore throat and had severe agranulocytosis (granulocyte count < 100/microliter). All had Graves' disease and were being treated with thiamazole 30 mg once a day. Thiamazole was discontinued and treatment with antibiotics initiated. None of the patients received granulocyte-colony stimulating factor (G-CSF). The mean recovery time of granulocytes was 9 days and there were no fatalities. Patients who receive antithyroid agents should be warned against the serious and potentially lethal side effect of agranulocytosis.

Adult↗
PubMed1999

Prospective randomized trial of docetaxel versus mitomycin plus vinblastine in patients with metastatic breast cancer progressing despite previous anthracycline-containing chemotherapy. 304 Study Group.

PURPOSE: This phase III study compared docetaxel with mitomycin plus vinblastine (MV) in patients with metastatic breast cancer (MBC) progressing despite previous anthracycline-containing chemotherapy. PATIENTS AND METHODS: Patients (n=392) were randomized to receive either docetaxel 100 mg/m2 intravenously (i.v.) every 3 weeks (n=203) or mitomycin 12 mg/m2 i.v. every 6 weeks plus vinblastine 6 mg/m2 i.v. every 3 weeks (n=189), for a maximum of 10 3-week cycles. RESULTS: In an intention-to-treat analysis, docetaxel produced significantly higher response rates than MV overall (30.0% v 11.6%; P < .0001), as well as in patients with visceral involvement (30% v 11%), liver metastases (33% v 7%), or resistance to previous anthracycline agents (30% v 7%). Median time to progression (TTP) and overall survival were significantly longer with docetaxel than MV (19 v 1 weeks, P=.001, and 1 1.4 v 8.7 months, P=.0097, respectively). Neutropenia grade 3/4 was more frequent with docetaxel (93.1 % v62.5%; P < .05); thrombocytopenia grade 3/4 was more frequent with MV (12.0% v 4.1%; P < .05). Severe acute or chronic nonhematologic adverse events were infrequent in both groups. Withdrawal rates because of adverse events (MV, 10.1%; docetaxel, 13.8%) or toxic death (MV, 1.6%; docetaxel, 2.0%) were similar in both groups. Quality-of-life analysis was limited by a number of factors, but results were similar in both groups. CONCLUSION: Docetaxel is significantly superior to MV in terms of response, TTP, and survival. The safety profiles of both therapies are manageable and tolerable. Docetaxel represents a clear treatment option for patients with MBC progressing despite previous anthracycline-containing chemotherapy.

Adult↗
PubMed1998

[Taxoids in ovarian and breast carcinoma: the role of the medical profession and the government].

After registration in 1993/1995 of paclitaxel and docetaxel for the treatment of ovarian and mammary carcinomas, the costliness of these drugs caused Dutch hospitals to adopt different policies for their use. This prompted the Minister of Health to ask the professional group of oncological internists to draw up a guideline for the use of taxoids, following which the government decided to supply extra money for the hospitals to use according to this guideline. Meanwhile new, contradictory study results have become known, still unpublished and in part originating from studies not yet conclude. The pharmaceutical industry advocates terminating the current research and maintaining the existing indications. However, patients are entitled to unbiased, complete research findings. The pathway for introducing new expensive drugs should be as follows: the professionals determine the indications for the new drug, the government pays attention to the financial consequences. The pharmaceutical industries should have no voice in the relevant decision-making.

Antineoplastic Agents, Phytogenic↗
PubMed1996

Carcino-embryonic antigen--no help with the differential diagnosis.

Two patients who were referred because of an increase in serum carcino-embryonic antigen (CEA) were diagnosed after a number of years as having a medullary thyroid carcinoma. The relationship between CEA and medullary thyroid carcinoma is discussed. The serum level of CEA is neither sensitive nor specific enough to serve as a diagnostic tool. Its determination, however, is useful in the follow-up of patients with carcinoma of the breast, colo-rectal carcinoma and medullary thyroid carcinoma.

Aged↗