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Biomedical subjects

E Engelsman

Publications and source records attributed to E Engelsman.

At least 19 recordsLinked to original sources
PubMed1991

Meningeal carcinomatosis in breast cancer. Prognostic factors and influence of treatment.

In 58 breast cancer patients with meningeal carcinomatosis (MC) pretreatment characteristics, clinical course, and response to treatment were evaluated. Forty-four patients were uniformly treated with intraventricular chemotherapy. Fourteen patients did not receive intraventricular treatment. In the intraventricularly treated group the median survival was 12 weeks. Multivariate analysis of the pretreatment characteristics of the intraventricularly treated patients demonstrated a prognostic significance with respect to survival for age older than 55 years, lung metastases, cranial nerve involvement, cerebrospinal fluid (CSF) glucose less than 2.5 mmol/l, and CSF protein 0.51 to 1.0 g/l. Based on the significance of these predicting factors a prognostic index (PI) identified four groups of patients with a median survival of 43 weeks, 22 weeks, 11 weeks, and 3 weeks, respectively. After 6 weeks of intraventricular treatment 22 patients showed a neurologic improvement or stabilization, and nine patients showed a worsening of the neurologic signs, whereas 13 patients (30%) had already died. The responders had a median additional survival of 5 months versus 1 month for nonresponders. No relation was found between survival and intensity of the intraventricular treatment after the first 6 weeks of treatment. Almost all long survivors had also received systemic treatment for systemic disease, whereas most patients who died within 6 months did not receive systemic therapy. Radiation therapy had no influence on the survival time. Early death due to the intensive treatment occurred in three patients. In 11 of the 17 patients who survived more than 4 months an often seriously debilitating late neurotoxicity developed. The survival curve of the nonintraventricularly treated patients appeared to be essentially the same as the curve of the intraventricularly treated patients. Using the same PI the predicted survival time was also the same as in the intraventricularly treated group. It is concluded that survival in MC from breast carcinoma may be more dependent on some pretreatment characteristics than on treatment intensity. On the basis of these pretreatment characteristics the survival time seems to be predictable. Finally, late neurotoxicity due to aggressive treatment leads to impairment of the quality of life in more than 50% of the long survivors. The exact value of intraventricular and systemic therapy in patients with MC still has to be determined.

Adult↗
PubMed1991

"Classical" CMF versus a 3-weekly intravenous CMF schedule in postmenopausal patients with advanced breast cancer. An EORTC Breast Cancer Co-operative Group Phase III Trial (10808).

The "classical" CMF (cyclophosphamide/methotrexate/5-fluorouracil) schedule was compared with a modified 3-weekly intravenous CMF schedule in postmenopausal patients with advanced breast cancer, as concern had arisen as to whether the classical schedule was the optimal way to give these drugs. The response rate with classical CMF was 48% compared with 29% for intravenous CMF (P = 0.003). Response duration was similar at 11 months, but survival longer for the classical schedule (17 versus 12 months, P = 0.016). We conclude that classical CMF is the superior regimen and attribute this to the higher dose intensity achieved.

Aged↗
PubMed1989

Locally advanced breast cancer: the contribution of cytotoxic and endocrine treatment to radiotherapy. An EORTC Breast Cancer Co-operative Group Trial (10792).

Patients with locally advanced carcinoma of the breast were randomized to receive either radiotherapy alone, radiotherapy + endocrine therapy, radiotherapy + chemotherapy or radiotherapy + endocrine therapy + chemotherapy. In 363 evaluable patients, time to first progression was delayed significantly by both endocrine treatment and chemotherapy, the greatest effect being achieved by the combination of endocrine treatment and chemotherapy. This effect was almost entirely due to a major effect of systemic treatment on time to loco-regional progression, for which the result is highly significant, rather than time to distant metastasis in which only a non-significant trend was observed. For survival, a trend was seen in favour of the combination of hormone treatment and chemotherapy, but this effect did not achieve statistical significance. This trial suggests that current endocrine and cytotoxic treatments are only of marginal value in improving the prognosis in locally advanced breast cancer.

Adult↗
PubMed1988

[Oncolytic agents].

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Antineoplastic Agents↗
PubMed1988

Production of and response to interleukin-2 in Graves' disease.

Interleukin-2 is a lymphokine which is believed to play a central role in the regulation of the immune response. The production of and response to interleukin-2 were determined in hyperthyroid Graves' patients together with thyroid function and serum thyrotropin receptor antibody, a marker of autoimmune activity. Interleukin-2 production by mitogen-induced peripheral blood mononuclears was markedly low in 24 of 29 patients when compared to controls. Five patients in remission had normal values. In nine patients followed during antithyroid drug therapy, interleukin-2 production returned gradually to normal levels within 4-6 months. This rise and the concomitant decrease in serum thyrotropin receptor antibody correlated with the decline in the free thyroxin index. Antithyroid drugs and triiodothyronine had no effect on interleukin-2 production in vitro. Mitogen-activated mononuclears from hyperthyroid Graves' patients did not proliferate as well as the controls in response to interleukin-2. However, seven patients treated with antithyroid drugs and three in remission responded normally. Flow cytometry using anti-Tac antibody revealed that the interleukin-2 receptor density on mononuclears from five patients was low. This parameter was normal in treated patients and those in remission. We conclude that the production of and response to interleukin-2 by peripheral blood mononuclears from hyperthyroid Graves' patients are poor, the latter being due to impaired receptor expression. Both aberrations are restored to normal by antithyroid drug therapy or in remission. The relative roles of the autoimmune process and thyroid function in modulating the interleukin-2 pathway and the question of whether antithyroid drugs act directly or through thyroid inhibition remain to be clarified.

Adult↗
PubMed1985

Combined cytotoxic and endocrine therapy in postmenopausal patients with advanced breast cancer. A randomized study of CMF vs CMF plus tamoxifen.

In this study 263 patients with advanced measurable breast cancer were randomized to receive cyclophosphamide, methotrexate and 5-fluorouracil (CMF) or CMF + tamoxifen (T). Each cycle of CMF (C, 100 mg/m2 p.o. days 1-14, M 40 mg/m2 i.v. days 1 and 8, F, 600 mg/m2 i.v. days 1 and 8) was repeated every 4 weeks. Tamoxifen, 20 mg twice daily, was given continuously. The treatment results have been assessed by external review for the 220 evaluable patients and were the following for the CMF and CMF + T groups, respectively: PD: 24 and 10%; NC: 27 and 15%; PR: 29 and 44%; and CR: 20 and 31%. The difference between response (CR + PR) rates is highly significant (P = 0.0001). The median duration of remission was 12 months in the CMF-treated group and 18 months in patients treated with CMF + T (P = 0.09). The median duration of survival was 19 months and 24 months respectively (P = 0.07). However, in the group of responders patients receiving CMF + T survived significantly longer than those who received CMF alone (32 months vs 21 months, P = 0.005). The addition of T appeared to be of benefit in all subgroups. The largest differences were seen in patients with the dominant site of disease in the viscera, in patients with a Karnofsky index of 100, and in patients of more than 60 yr of age. The amount of CMF given was identical in the two treatment groups and there was a trend toward a decrease in dose with increasing age. No relationship between response and dose given was observed. In conclusion, the simultaneous use of T and CMF improves the therapeutic results in patients with advanced breast cancer.

Adult↗
PubMed1985

Adjuvant chemo- and hormonal therapy in locally advanced breast cancer: a randomized clinical study.

UNLABELLED: Between 1977 and 1980, 118 breast cancer patients with locally advanced disease, T3B-4, any N, M0 or T1-3, tumor positive axillary apex biopsy, were randomized to one of three arms: I: radiotherapy (RT) to the breast and adjacent lymph node areas; II: RT followed by 12 cycles of cyclophosphamide, methotrexate, 5 fluorouracil (CMF) and tamoxifen during the chemotherapy period; III: 2 cycles of adriamycin and vincristine (AV), alternated with 2 cycles of CMF, then RT, followed by another 4 cycles of AV, alternated with 4 CMF; tamoxifen during the entire treatment period. The median follow-up period was 5 1/2 years. The adjuvant chemo- and hormonal therapy did not improve the overall survival; the 5-year survival was 37% for all three treatment arms. There was no statistically significant difference in RFS between the three modalities, nor when arm I was compared to arm II and III together, p = 0.11. Local recurrence (LR) was observed in 24 of the 86 patients (28%) who had reached complete remission (CR). LR was not statistically different over the three treatment arms. In 18 of the 24 patients with LR, distant metastases appeared within a few months from the local recurrence. In arm III, the CR rate after 4 cycles AV plus CMF and RT hardly changed after another 8 cycles of chemotherapy. The menopausal status did not influence the treatment results. Dose reduction in more than 4 cycles of chemotherapy was accompanied by better results, p = 0.04. IN CONCLUSION: adjuvant chemo- and hormonal therapy did not improve RFS and overall survival. These findings do not support the routine use of adjuvant chemo- and endocrine therapy for inoperable breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Placental-site trophoblastic tumor: diagnosis, treatment, and biological behavior.

The clinical history of a patient with a placental-site trophoblastic tumor is presented. The diagnostic and therapeutic value of dilatation and curettage, the human chorionic gonadotropin titer, hysteroscopy, laparoscopy, chemotherapy, and hysterectomy is discussed, as well as the possibility of metastatic disease. In this patient there was radiological evidence of pulmonary metastasis with apparent spontaneous regression. A proposal is made to change the name of this disease to gestational trophoblastic neoplasia of low potential malignancy.

Adult↗
PubMed1978

Pilot study on adjuvant chemotherapy and hormonal therapy for irradiated inoperable breast cancer.

A pilot study of adjuvant chemotherapy and hormonal therapy for inoperable breast cancer was performed. The patients were known to have a bad prognosis because of occult generalized disease. At the time of first treatment, the patients selected showed no signs of systemic disease. Local control of the breast and regional lymph nodes was achieved by radiotherapy. Adjuvant therapy consisted of alternating chemotherapy and tomoxifen. Adriamycin was dropped from the treatment schedule after 1 year because of enchanced radiation side-effects. Meanwhile the radiotherapy schedule was changed. A questionable control group was formed by patients radiated in the same period who failed to meet the entry criteria for various reasons. At presents, patients in the treated group show a better relapse-free survival than patients in the control group. The differences is statistically significant for premenopausal women. There is no significant difference in the overall survival between the treated group and the control group after an average follow-up of 2 years. After 2 years, the pilot study was closed. A randomized controlled clinical trial was started. In one group of this trial intensive chemotherapy is the first treatment employed.

Antineoplastic Agents↗
PubMed1975

Comparative trial of nafoxidine and ethinyloestradiol in advanced breast cancer: an E.O.R.T.C. study.

A randomized clinical trial of nafoxidine, a non-steroidal oestrogen antagonist, and ethinyloestradiol in postmenopausal patients with advanced breast cancer produced objective remissions in 31% of 49 women receiving nafoxidine and in 14% of 49 receiving ethinyloestradiol. The differences in remission rates was almost significant (0.05 less than P less than 0.10). Life-threatening complications were more frequent with ethinyloestradiol than with nafoxidine but the latter produced specific toxic reactions on skin and hair that may limit its practical usefulness. Synthetic oestrogen antagonists may occupy a privileged place in the treatment of breast cancer, and other representatives of this new class of compounds should be accurately assessed in randomized clinical trials.

Administration, Oral↗
PubMed1975

Controlled clinical trial of L-dopa and nafoxidine in advanced breast cancer: an E.O.R.T.C. study.

L-Dopa lowers plasma prolactin levels, and there have been reports that patients with advanced breast cancer have been successfully treated with L-dopa. To test the potential value of L-dopa in this disease a randomized clinical trial of L-dopa and nafoxidine (as the reference compound) was conducted in postmenopausal women with advanced breast cancer. Objective remissions were obtained in sever out of 36 patients (19%) treated with nafoxidine but in none out of 40 patients treated with L-dopa. L-Dopa in the dose schedule used seems to be ineffective in advanced breast cancer.

Administration, Oral↗