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Biomedical subjects

H Brincker

Publications and source records attributed to H Brincker.

At least 55 records · Page 3Linked to original sources
PubMed1988

Adjuvant therapy of premenopausal and menopausal high-risk breast cancer patients. Present status of the Danish Breast Cancer Cooperative Group Trials 77-B and 82-B.

From September 1977 to November 1987 high-risk (i.e. with positive axillary lymph nodes, or tumor size greater than 5 cm or skin/facia invasion) premenopausal and menopausal breast cancer patients have been included in 2 randomized trials. In both trials the primary surgical treatment was total mastectomy with axillary sampling. In the first trial (DBCG 77-B) 1034 patients all received postoperative radiotherapy (RT) and were further randomized to 1) no systemic treatment (0), 2) cyclophosphamide (C), or 3) cyclophosphamide + methotrexate + 5-fluorouracil (CMF). The chemotherapy was given for 1 year. With a median observation time of 7 years the actuarial survival after 9 years is 50, 60 and 65% respectively. Retrospectively, the survival benefit was observed to be most pronounced in patients with tumor size less than or equal to 5 cm and with less than or equal to 3 positive lymph nodes. In the subsequent study initiated in 1982 (82-B) all patients received CMF for 9 months. Furthermore they were randomized to 1) RT, 2) no further treatment, or 3) tamoxifen (TAM) for 1 year. As of November 1, 1987, 1308 patients have been included. At 4 years and with a median observation time of 2 years the survival is similar in the 3 groups. In conclusion, in high-risk premenopausal and menopausal patients adjuvant chemotherapy combined with RT resulted in a 20-30% relative reduction in mortality at 9 years compared with RT alone. Preliminary analysis of adjuvant CMF + RT, compared with CMF alone or with CMF + TAM, shows after a median observation time of more than 2 years no significant survival differences.

Adult↗
PubMed1988

Postmastectomy irradiation in high-risk breast cancer patients. Present status of the Danish Breast Cancer Cooperative Group trials.

All pre- and postmenopausal high-risk breast cancer patients in the protocols DBCG 77 of the Danish Breast Cancer Cooperative Group received postmastectomy irradiation before randomization to either adjuvant systemic therapy or no such treatment. The actuarial loco-regional recurrence rate at 9 years was 6-17%, with the lowest rate in patients who also received additional adjuvant chemotherapy or tamoxifen. In a subsequent study (DBCG 82) the role of postmastectomy irradiation together with systemic treatment was evaluated in high-risk patients. Pre- and menopausal patients were randomized to postmastectomy irradiation + CMF (cyclophosphamide, methotrexate, 5-fluorouracil), CMF alone or CMF + TAM (tamoxifen). Postmenopausal patients were randomized to postmastectomy irradiation + TAM, TAM or CMF + TAM. At 4 years the loco-regional recurrence rate was significantly lower in the irradiated patients (5-7% vs. 23-33%). Further, disease-free survival was significantly improved in both pre- and postmenopausal irradiated patients compared with those who had only systemic treatment. At present, there are no significant differences between survival in the treatment groups. Thus, adjuvant systemic treatment alone (chemotherapy and/or tamoxifen) did not prevent loco-regional recurrences in high-risk patients after mastectomy and axillary lymph node sampling. However, a longer observation time is necessary to evaluate the consequence of primary optimal loco-regional tumour control in high-risk breast cancer patients with respect to survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Distant recurrence in breast cancer. Survival expectations and first choice of chemotherapy regimen.

Controversial questions in recurrent breast cancer include the magnitude of the survival benefit of combination chemotherapy and the best choice of first line chemotherapy. Data from the files of the Danish Breast Cancer Cooperative Group (DBCG) show that with current systemic treatment median survival after distant recurrence is 19 months. Since historical data from the pre-chemotherapy era indicate a median survival of 12 months, the survival benefit of standard chemotherapy appears to be around 7 months in the average patient. The DBCG trial 80-R2 is the largest randomized trial of CAF (cyclophosphamide, doxorubicin, 5-fluorouracil) versus CMF (cyclophosphamide, methotrexate, 5-fluorouracil) in recurrent breast cancer. A review of this study and 6 other similar studies shows that CAF is clearly superior to CMF in terms of better tumor shrinkage, prolonged overall time to progression, and decreased need of secondary therapy. The adverse effects of the two treatments are largely comparable, but CAF causes severe alopecia and is more expensive than CMF. On balance, the existing evidence indicates that CAF rather than CMF should be chosen as first line chemotherapy in recurrent breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Solid tumors preceding or following sarcoidosis.

Eight cases of sarcoidosis diagnosed after a preceding malignant solid tumor are presented. An analysis of these eight cases along with four previously reported cases was unable to answer the question whether in some cases the development of sarcoidosis may be triggered or modified by a preceding treatment of a malignant tumor. However, in the reverse situation--sarcoidosis preceding cancer--an analysis of 23 such cases from the literature suggests that sarcoidosis preceding cancer appears to be of the chronic active variety and that lung and breast cancer may occur more often than expected after sarcoidosis. Thus, it is conceivable that the immunologic abnormalities associated with sarcoidosis may somehow promote the development of certain malignant tumors. True sarcoidosis may be confused with local sarcoid reactions in cancer patients. One such case is reported in which the finding of a regional sarcoid reaction to a solitary lung metastasis from a uterine adenocarcinoma led to insufficient treatment in the belief that the patient had systemic sarcoidosis.

Adult↗
PubMed1987

Cyclic alternating polychemotherapy with or without upper and lower half-body irradiation in small cell anaplastic lung cancer. A randomized study.

Ninety-six patients with small cell anaplastic lung carcinoma were given monthly chemotherapy with vincristine-doxorubicin-cyclophosphamide alternating with CCNU-methotrexate-etoposide for 18 months or until evidence of progressive disease. Forty-four patients were randomized to chemotherapy alone and 52 patients to chemotherapy plus 600 cGy of both upper and lower half-body irradiation given day 60 and 100, respectively. In 78 evaluable patients surviving more than 100 days the overall response rate was identical in the two arms of the study, 68% vs. 66%. However, time to progression was significantly shorter in the irradiated patients (P = 0.05). Only 25% of the irradiated patients tolerated greater than or equal to 75% of the scheduled dose of chemotherapy, against 91% of the non-irradiated patients (P = 0.0001). Thus, half-body irradiation was associated with a shorter time to progression and a decreased ability to give maintenance chemotherapy at proposed doses.

Adult↗
PubMed1987

Chemotherapy of progressive hairy-cell leukaemia.

5 patients with hairy-cell leukaemia were treated with chemotherapy. 3 of them received multiple courses of CHOP (cyclophosphamide-doxorubicin-vincristine-prednisolone); 1 patient received cyclophosphamide monotherapy for 6 months. The 5th patient developed a Mikulicz's syndrome after splenectomy and was initially treated with cyclophosphamide monotherapy, then received 1 course of CHOP, and finally 9 courses of intermediate-dose methotrexate. 1 complete remission (45 months+) and 3 partial remissions (75+, 68, 32+ months) were observed, while 1 patient had progressive disease. Our results indicate that chemotherapy may be a valuable alternative to alpha-interferon in the treatment of hairy-cell leukaemia progressing after splenectomy.

Adult↗
PubMed1987

Evidence of a castration-mediated effect of adjuvant cytotoxic chemotherapy in premenopausal breast cancer.

This prospective randomized trial, conducted by the Danish Breast Cancer Cooperative Group, is the largest study, so far, of adjuvant chemotherapy in premenopausal breast cancer. The trial is unique in that it is nationwide and based on a nonselected population of patients, and is the only adjuvant trial studying the effect of cyclophosphamide monotherapy. After total mastectomy with axillary node sampling, followed by local radiotherapy, 1,032 pre- and perimenopausal women with operable breast cancer were randomized to observation alone, or to adjuvant chemotherapy for 1 year with either cyclophosphamide monotherapy or with a combination of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF). As of January 1987, median follow-up was 68 months. From early on both cyclophosphamide alone and CMF were found to improve recurrence-free survival (RFS) significantly and to a similar degree (P = .0001). However, an overall survival advantage did not become evident until 5 years after the start of treatment. So far, this advantage appears to be more pronounced in CMF (P = .0065) than in cyclophosphamide-only patients (P = .08). Thus, the study confirms the findings of the National Surgical Adjuvant Breast Project (NSABP) and Milan trials that adjuvant chemotherapy prolongs the survival of premenopausal women with early breast cancer. A retrospective analysis revealed that, in contrast with CMF, cyclophosphamide alone did not improve RFS significantly in subsets of patients without amenorrhea, with estrogen-receptor (ER) negative tumors, and with tumors of low histological differentiation. Assuming that cyclophosphamide alone is a less tumoricidal treatment than CMF, these findings suggest that the effect of adjuvant cytotoxic chemotherapy is mediated partly through chemical castration, and partly through a purely cytotoxic effect.

Adult↗
PubMed1987

Problems associated with comparisons of response-defined subsets of patients in randomized trials. Treatment-related bias and response migration.

Subset analysis may be justified between various arms of randomized trials as long as subsets are defined by variables which do not cause distortion of other prognostic factors. However, bias will occur when treatment response is used to define a subset of patients in which the results of the same treatment are analyzed. Thus, comparisons between groups of responders in randomized studies are just as inherently biased as comparisons between responders and non-responders. Using a constructed example the effects of treatment-related bias on the interpretation of trial results are demonstrated, and the concept of response migration is introduced. It is shown that in randomized trials the only unbiased measures of treatment efficacy are response rate, overall time to progression, and overall survival.

Clinical Trials as Topic↗
PubMed1986

Fifty-five patient years' experience with a totally implanted system for intravenous chemotherapy.

A subcutaneously implanted injection system represents a new method of central venous access. Seventy-eight injection capsules were implanted in 75 cancer patients undergoing intermittent chemotherapy. The actuarial median functional survival of the injection capsules was 16 months, and with a cumulative function time of 55 patient years the complication rate was only one complication every 990 days. No cases of septicemia and few cases of local infection or clotting of the system were seen. Patient activities were not restricted, and maintenance of the system between treatment courses was unnecessary. However, in 9% of the implants a tendency to erosion through the skin was observed, necessitating explantation or reimplantation. Injection capsules seem to be particularly suited for intermittent chemotherapy, including short-term infusions and blood sampling.

Adolescent↗
PubMed1986

Medroxyprogesterone acetate and prednisone in advanced breast cancer. A randomized trial.

In a randomised trial patients with progressive metastatic breast cancer were allocated to one of three different treatments. A: Prednisone 10 mg X 3 daily. B: Medroxyprogesterone acetate (MPA) orally 500 mg daily. C: MPA i.m. 1000 mg daily for 3 weeks followed by 500 mg i.m. weekly. The study included 150 patients and was well-balanced with respect to different prognostic parameters. Most patients (83%) were postmenopausal, and 95% had previously received chemo- or hormonal therapy. In the MPA treated patients, analysis of serum MPA levels was performed once a month. The response rates were 4.6, 7.9 and 12.5% in treatments A, B and C, respectively. This difference was not statistically significant (P greater than 0.05). Furthermore, the follow-up of serum MPA levels revealed no significant difference between responders and non-responders. Analysis of time to progression did not indicate any advantage of MPA over prednisone, irrespective of MPA schedule. In accordance with these data, there was no difference as regards survival in the three groups. In conclusion, the study indicated that MPA is not superior to prednisone in this group of heavily pretreated patients with advanced breast cancer.

Administration, Oral↗
PubMed1986

Sarcoid reactions in malignant tumours.

Tumour-related tissue reactions resulting in the formation of epithelioid-cell granulomas have been known for almost 70 years. Such sarcoid reactions may occur in lymph-nodes draining an area housing a malignant tumour, in the tumour itself, and even in non-regional tissues. Overall, sarcoid reactions occur in 4.4% of carcinomas, in 13.8% of patients with Hodgkin's disease, and in 7.3% of cases of non-Hodgkin lymphomas. Similar histologic changes in sarcoma appear to be extremely rare. Most probably, sarcoid reactions are caused by antigenic factors derived from the tumour cells, eliciting an immunological hypersensitivity reaction leading to the formation of epithelioid-cell granulomas. Sarcoid reactions may be a marker of an immunologically mediated antitumour response of macrophages activated by T-lymphocytes, and in Hodgkin's disease there is evidence that patients with sarcoid reactions have a better prognosis. On occasion sarcoid reactions may be so extensive that they complicate the diagnosis of an underlying malignant disease. Problems may also arise of distinguishing between tumour-related sarcoid reactions and true systemic sarcoidosis.

Antigens, Neoplasm↗
PubMed1986

The sarcoidosis-lymphoma syndrome.

Analysis of 17 cases of coexistent sarcoidosis and malignant lymphoproliferative disease, supplemented with 29 similar cases reported in the literature indicates that this association is not fortuitous. In addition, significantly more malignancies other than lymphoma were found in this group of patients. A sarcoidosis-lymphoma syndrome appears to exist in which malignant lympho-proliferative disease develops at least 5.5 times more often than expected in middle-aged patients with chronic active sarcoidosis, possibly as a consequence of the immunologic abnormalities observed in the latter disease.

Adult↗
PubMed1986

Combined endocrine treatment of postmenopausal patients with advanced breast cancer. A randomized trial of tamoxifen vs. tamoxifen plus aminoglutethimide and hydrocortisone.

The therapeutic efficacy of combined endocrine therapy with tamoxifen, aminoglutethimide and hydrocortisone (T+AG+H) was evaluated against treatment with tamoxifen (T) alone in 210 patients above 65 years of age with metastatic breast cancer. The treatment results have been assessed for the 166 fully evaluable patients and were the following for the T and T+AG+H groups, respectively: PD: 31 and 35%; NC: 35 and 37%; PR: 13 and 16%; and CR: 21 and 12%. The overall treatment results are not statistically different (p = 0.35) and the 95% C.L. of the difference of the response rates are -8% to +20%. The median duration of remission was approximately 24 months in both treatment groups (p = 0.31). The time to treatment failure was comparable with median values of 10 and 8 months in the T and the T+AG+H groups respectively (p = 0.17). Toxicity was more frequent and severe in the combined treatment group and could in most instances be attributed to treatment with AG+H. In conclusion, the simultaneous use of T and AG and H does not seem to improve the therapeutic results in postmenopausal patients with advanced breast cancer.

Aged↗
PubMed1986

Adjuvant tamoxifen in postmenopausal high-risk breast cancer patients: present status of Danish Breast Cancer Cooperative Group trials.

The aim of the present study was to analyze the efficacy of adjuvant tamoxifen (TAM) in postmenopausal patients with high-risk breast cancer. The primary surgical treatment was total mastectomy with axillary sampling. There were 1,650 eligible patients; 829 were randomized to receive postoperative radiotherapy (RT) and 821, to receive RT + TAM (10 mg three times daily for 1 yr). The 2 groups were identical with respect to age, tumor size, number of positive lymph nodes, degree of anaplasia, and estrogen and progesterone receptor content. Overall recurrence-free survival at 6 years was 39% in the RT group, compared to 48% in the RT + TAM group (P = 0.0008), but there was no significant difference in survival (P = 0.14). From retrospective analyses of recurrence-free survival according to prognostic variables, it appears that 4 subgroups of patients benefited from adjuvant TAM: those less than 69 years of age, those with 4 or more positive nodes, those with grade I-II tumors, and those with high estrogen receptor values (greater than 100 fmol/mg cytosol protein).

Aged↗
PubMed1985

Estimate of overall treatment results in acute nonlymphocytic leukemia based on age-specific rates of incidence and of complete remission.

It is widely assumed that most patients with acute nonlymphocytic leukemia (ANLL) are less than 60 years old, that greater than 50% of all patients can now achieve a complete remission (CR), and that bone marrow transplantation (BMT) represents a significant therapeutic breakthrough in this disease. New epidemiological data, presented in this study, show that the median age of patients with ANLL is 62-64 years, with 54%-59% of the patients being greater than 60 years old. When combining age-specific incidence data with age-specific data on CR derived from the recent literature, it can be calculated that the cumulated rate of CR for all ages combined will be only between 35.3% and 49.2% with current therapy. It can also be calculated that BMT with its present limitations can at most cure 1.44%-2.5% of all patients with ANLL. These findings suggest that some of the accepted conceptions in ANLL regarding age distribution of patients, cumulated rates of CR, and value of BMT cannot stand up to closer scrutiny. Treatment priorities and resource allocation in ANLL should be reconsidered, and more attention should be given to solving the problems of treatment in elderly patients.

Acute Disease↗