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Biomedical subjects

B Cedermark

Publications and source records attributed to B Cedermark.

At least 55 records · Page 3Linked to original sources

Randomized trial of adjuvant tamoxifen combined with postoperative radiation therapy or adjuvant chemotherapy in postmenopausal breast cancer.

From 1976 to 1984, 427 postmenopausal women with high-risk breast cancer (pN + or pT greater than 30 mm) were randomized between postoperative radiation therapy (RT), radiation therapy plus tamoxifen (RT-TAM), adjuvant chemotherapy (CT), or chemotherapy plus tamoxifen (CT-TAM). Surgery was a modified radical mastectomy in all cases. The radiation therapy was given with high-voltage techniques and included the chest wall and regional nodes. The dose was 4600 cGy/4 1/2 weeks. Tamoxifen was given at a dose of 40 mg daily for 2 years. The adjuvant chemotherapy consisted of 12 cycles of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) (or chlorambucil, methotrexate, and 5-fluorouracil [LMF] for patients entered before 1978). At a median follow-up time of 6 1/2 years the recurrence-free survival was significantly better for patients allocated to radiation therapy compared to chemotherapy and for patients allocated to tamoxifen compared to no adjuvant endocrine treatment (P less than 0.01). At 10 years the recurrence-free survival for patients in the RT-TAM, RT, CT-TAM, and CT groups was 63%, 57%, 47%, and 31%, respectively. A significant reduction of treatment failures with tamoxifen was only observed among patients with estrogen receptor-positive tumors. The overall survival difference in favor of patients allocated to radiation therapy or tamoxifen was not significant: the respective survival percentage at 10 years in the RT-TAM, RT, CT-TAM, and CT group was 65%, 62%, 52%, and 50%. The results indicate that postoperative radiation therapy continues to play an important role in the primary management of postmenopausal women with high-risk breast cancer and that the addition of tamoxifen may further improve the results among ER-positive patients.

Aged↗

Adrenocortical carcinoma. A retrospective study of a rare tumor with a poor prognosis.

A retrospective study was performed on 54 patients diagnosed as having adrenocortical carcinoma during 1974-1983. The initial symptoms were often diffuse: abdominal pain, weight loss, or fever, and more than 60% of the patients showed no evidence of overproduction of hormone. The median tumor diameter was 13 cm and almost half of the tumors had metastasized at diagnosis. A radical tumor resection could be performed in less than 50% of the patients, and at histopathological re-examination some tumors were not conclusively verified as malignant. Capsular invasion, nuclear pleomorphism and mitoses were found more commonly in patients who succumbed to the disease. Seven of 29 patients treated with chemotherapy showed an objective response and two of them are still alive and free of disease. The overall 5-year-survival rate was 19%, compared with 45% for patients with radically resected tumors. Patients with no biochemical signs of overproduction of adrenocortical hormone appeared to have a better prognosis than those with hormone excess. Together with increased use of ultrasound and computed tomography, a urinary steroid profile might hopefully contribute to earlier discovery of these often clinically silent tumors. However, it remains to be determined whether these diagnostic improvements, together with more aggressive surgery and adrenolytic chemotherapy, can improve the poor prognosis.

Adolescent↗

Adjuvant tamoxifen in early breast cancer: occurrence of new primary cancers.

The frequency of new primary cancers was studied in 1846 postmenopausal patients included in a randomised trial of tamoxifen as an adjunct to primary surgery for early breast cancer. The median follow-up was 4.5 years (range 0.5-10.5 years). The number of new cancers in the tamoxifen group (n = 57) did not differ significantly from that in the control group (n = 70). However, in tamoxifen patients second breast cancers occurred less often and endometrial cancer occurred more often than in the controls. The increase in endometrial cancers was probably related to the agonistic oestrogenic effects of tamoxifen and was most pronounced in those treated for over 2 years.

Adenocarcinoma↗

Implantable catheter system for long-term intravenous chemotherapy.

Fifty-three implantable catheter systems (Port-A-Cath) were placed subcutaneously in 48 patients with malignant tumours. This device consists of a stainless steel chamber covered by a silicone membrane connected to a silicone catheter placed in a central vein. All systems were used for administration of chemotherapy. The mean function time was 187 days (range 0-867). Complications necessitating reoperation occurred in six patients. In three cases, the catheter occluded from thromboses. In two patients, wound dehiscence occurred, and in one a wound infection developed. In one case, the catheter was disconnected from the port. Four patients who had had the port removed later received new ports. One patient had the second port removed and was given a third catheter system. It is concluded that subcutaneously implantable injection ports constitute a safe and convenient access for long-term intravenous chemotherapy. The complication rate is low, and it should be possible to avoid most recorded complications in the future.

Adolescent↗

Insulin and C-peptide co-localization in the beta granules of normal human pancreas and insulinomas. A quantitative immunocytochemical approach.

It has been shown, by using the immunogold technique, that C-peptide and insulin are co-localized in the mature granules of human pancreatic beta cells and insulinomas with typical granules. The mean gold bead densities of both C-peptide and insulin were at least twice as high in the normal pancreas when compared with the insulinomas. The mean granule diameter of the insulinoma cells (D = 0.30 +/- 0.12 micron) was smaller than that of human pancreatic cells (D = 0.45 +/- 0.15 micron). The morphometric data indicate that each of the antigens (C-peptide and insulin) is distributed similarly in the halos and the dense cores of the beta granules. Thus, no topological segregation of these two antigens occurs within the beta granules of either normal human pancreas or insulinomas.

Adenoma, Islet Cell↗

The clinical use of monoclonal antibodies, MAb 17-1A, in the treatment of patients with metastatic colorectal carcinoma.

Increasing doses of MAb 17-1A (mouse IgG2A) have been given for therapy of patients with metastatic colorectal carcinoma (n = 28). Serum half-life (T beta 1/2) of MAb 17-1A after a single infusion was about 24 h. A constant serum level of MAb 17-1A could be maintained for a long time period by infusions every 2-3 days. Patients received 500 mg 3 days a week for 12 weeks (total dose 12 g). Side effects were mild and dose related but never required medical intervention except for three times (out of 243 infusions) when allergic reactions appeared. All patients developed IgM and IgG antibodies. Two patients experienced immune complex-related symptoms. Six out of 22 evaluable patients (27%) had objective evidence of tumor cell regression/lysis. One of these achieved a complete remission. Median survival for all patients was 12 months, for responding patients 19 months and for non-responding 11 months. 5/17 patients were studied for the development of anti-anti-idiotypic antibodies (Ab3). The presence of Ab3 in serum correlated favourably to the clinical outcome of the disease.

Adult↗

Oral treatment with RU 41.740 (Biostim) in patients with advanced colorectal cancer: influence on the blood lymphocyte population.

Twelve patients with advanced colorectal carcinoma received oral treatment with RU 41.740, an immunomodulatory drug obtained from Klebsiella pneumoniae. The patients received three courses of RU 41.740, each consisting of 8 mg daily for 7 consecutive days, with free intervals of 3 weeks. This treatment did not significantly change the distribution of various lymphocyte subsets in the blood or the NK activity of the lymphocytes. However, PHA reactivity of purified lymphocytes increased significantly and exhibited a 2-3-fold enhancement 3 weeks after the last course. Such an increase was not observed in lymphocyte preparations which were not depleted of monocytes. It is concluded that 41.740 may be immunopharmacologically active in man when administered by the oral route.

Administration, Oral↗

Radiotherapy, chemotherapy, and tamoxifen as adjuncts to surgery in early breast cancer: a summary of three randomized trials.

The paper summarizes up-dated results of three randomized adjuvant trials from the Stockholm Breast Cancer Group. The objective of all studies included an evaluation of the role of megavoltage radiation in the primary management of patients with early breast cancer. The first trial was started in 1971 and included 960 pre- and postmenopausal patients with operable disease. The study compared adjuvant radiotherapy with surgery alone. All patients were treated with a modified radical mastectomy. There was a sustained improvement of the recurrence-free survival with radiotherapy (p less than 0.001). Among node positive cases radiation reduced the frequency of both loco-regional recurrence (p less than 0.001) and distant metastasis (p less than 0.01). This observation indicates that distant dissemination in subgroups of patients can originate from uncontrolled local deposits of tumor cells, for instance in the regional lymph nodes. No adverse effect from radiation on long-term survival was observed. The second study was started in 1976 and compared postmastectomy radiation with adjuvant chemotherapy in pre- and postmenopausal high-risk patients. At a mean follow-up of 6 1/2 years there was no significant difference in recurrence-free survival between the two treatments. However, postmenopausal patients fared better with radiotherapy (p less than 0.01). In this subgroup, radiation was more effective than adjuvant chemotherapy in reducing both distant metastases (p less than 0.01) and loco-regional recurrences (p less than 0.001). In the third trial--which only included postmenopausal patients--2 years of adjuvant tamoxifen was compared with no adjuvant endocrine treatment. The number of treatment failures was significantly reduced with tamoxifen (p less than 0.01) but there was no significant overall survival benefit. Subset analysis indicated that tamoxifen improved the recurrence-free survival among patients treated with adjuvant chemotherapy (p less than 0.01) but only to a level close to that achieved with radiotherapy alone. Addition of tamoxifen to radiotherapy failed to further increase the recurrence-free survival.

Aged↗

The relationship between hormone receptor content and the effect of adjuvant tamoxifen in operable breast cancer.

The relationship between hormone receptor status and the effect of adjuvant tamoxifen in early breast cancer remains controversial. This article presents the results of a randomized trial of adjuvant tamoxifen (40 mg daily for 2 years) versus no adjuvant endocrine therapy in postmenopausal patients. During 1976 to 1984, 1,407 patients were included in the study. Of these, 427 (30%) had high-risk tumors (pN + or pT greater than 30 mm) and were included in a concurrent randomized comparison of postoperative radiotherapy versus adjuvant polychemotherapy. The mean follow-up time was 61/2 years. Tamoxifen improved the recurrence-free survival (RFS) (P less than .01), but the overall survival difference in favor of the tamoxifen-allocated patients was not significant. Data on estrogen (ER) and progesterone receptor (PgR) content were available in 750 patients. Their mean follow-up time was 41/2 years. The effect of tamoxifen was significantly related to ER level (P less than .01). No benefit with tamoxifen was observed among ER-negative patients. The relation to PgR level was of borderline significance (P = .06). Multivariate analysis indicated that most of the interaction between treatment and receptor content was explained by the interaction with ER (P less than .01). The PgR status appeared to modify the effect of tamoxifen among the ER-positive patients and the greatest effect was observed among patients who were positive for both receptors. However, the additional predictive information provided by the PgR assay did not help to identify an unresponsive subgroup of patients.

Aged↗

Chromogranin A and B and secretogranin II in bronchial and intestinal carcinoids.

Carcinoid tumours (bronchial and intestinal) were analyzed by immunoblotting for the presence of chromogranin A, B and secretogranin II. In all tumours an antigen corresponding in electrophoretic behaviour to adrenal chromogranin A was present. Lung carcinoids (3 out of 5) contained a relatively high concentration of a proteoglycan form of this antigen in addition. Chromogranin B was found in all tumours. In one and two dimensional immunoblotting it appeared identical to the corresponding adrenal antigen. Secretogranin II was also present, however concentrations (especially in intestinal carcinoids) were low and variable. Furthermore, in intestinal tumours it differed from the adrenal antigen by having a slightly higher molecular size and a more alkaline pI. Immunohistochemistry revealed that the tumour tissues stained positively for all three antigens. For secretogranin II the staining in intestinal tumours was relatively weak and quite variable. These results should provide a defined basis for immunohistochemical screening of carcinoids for the chromogranin/secretogranin antigens.

Bronchial Neoplasms↗

Two randomised phase II trials of intermittent intravenous versus subcutaneous alpha-2 interferon alone (trial 1) and in combination with 5-fluorouracil (trial 2) in advanced colorectal cancer.

Sixty-five patients with advanced colorectal cancer were randomised to one of two schedules of recombinant alpha-2 interferon (IFN). In the first study, 36 patients received single-agent IFN, either 50 X 10(6) U/m2 intravenously on 5 consecutive days every 4 weeks, or 20 X 10(6) U/m2 subcutaneously three times per week. No tumour responses were seen and toxicity was unacceptable. In the second study, 29 patients received IFN in two similar schedules, but the dose of IFN was reduced to 20 X 10(6) U/m2 per day in the intravenous arm and to 5 X 10(6) U/m2 per day in the subcutaneous arm. In addition these patients were administered intravenous 5-Fluorouracil (5-FU), 250-500 mg/m2 per day on the first 5 days of each 4-weekly cycle. Although the toxicity of this second study was tolerable, only one short-lived partial remission was observed. Alpha-2 interferon, alone or in combination with 5-FU, is ineffective in advanced colorectal cancer.

Adenocarcinoma↗

The Stockholm trial on adjuvant tamoxifen in early breast cancer. Correlation between estrogen receptor level and treatment effect.

The paper presents interim results of an on-going randomized trial of adjuvant tamoxifen (40 mg daily for 2 years) versus no endocrine adjuvant therapy in postmenopausal women with early breast cancer. A total of 1407 patients were included in the study between November 1976 through June 1984. Estrogen receptor (ER) data were available on 1184 patients (84%). The median follow-up was 53 months. Adjuvant tamoxifen increased the recurrence-free interval (P less than 0.01) but had no significant effect on overall survival. Treatment failures were reduced by 25% (P less than 0.01) and deaths by 7% (P greater than 0.05). Tamoxifen mainly decreased the frequency of loco-regional recurrence whereas distant metastases were less affected. The treatment effect was independent of tumor stage but was significantly related to the estrogen receptor (ER) content of the primary tumor. Tamoxifen appeared ineffective among ER negative patients, and the greatest effect was seen among those with high levels of ER. The results indicate that the main mechanism of action of adjuvant tamoxifen is similar to that suggested in advanced disease, i.e. an interaction with the estrogen receptor.

Aged↗

Enteral and parenteral nutrition in anorectic patients with advanced gastrointestinal cancer.

Seventeen patients with advanced, noncurable gastrointestinal cancer with symptoms of anorexia and malnutrition were treated with controlled enteral or total parenteral nutrition over a 3-week period. Eleven patients received enteral and six parenteral nutrition. The nutrition was given with 30-40 kcal/kg b.w. daily. No anticancer treatment was given. Before and after the treatment period, the patients were assessed regarding their nutritional, immunological, and performance status. None of the studied nutritional parameters changed significantly over the 3-week period and there was no clear indication of an improved lymphocyte reactivity. There was a tendency toward improvement in performance status for the patients on enteral nutrition, while the reverse seemed to be true for the parenteral group. It is concluded that nutritional support may halt the progressive malnutrition often seen in patients with cancer and serve as a palliative treatment in selected patients.

Aged↗

Preoperative short-term radiotherapy in rectal carcinoma. A preliminary report of a prospective randomized study.

Between 1980 and 1983, 373 patients with clinically resectable rectal adenocarcinoma entered a prospective randomized study aimed to evaluate the effect of short-term preoperative radiotherapy. Protocol violations were identified in 21 instances. Of the remaining 352 patients, 182 were randomized to surgical treatment only (S-group). Immediately, before surgery, 170 patients were irradiated to the pelvic region with 25 Gy (2500 rad) during a 5-day period (RT-group). Of these patients, 59% underwent abdominoperineal excision, 38% anterior resection, and 3% laparotomy only. At surgery distant metastases were discovered in 32 patients (9%). There were no significant differences between the groups in the distribution of age, sex, operative methods, and tumor stage according to the original Dukes' classification. During the follow-up time, ranging between 6 months and 3 years, tumor recurrence occurred in 35 patients, 19 in the S-group and 16 in the RT-group. Fifteen patients in the S-group had pelvic recurrence compared to 10 patients in the RT-group. Distant metastases occurred in six and eight patients, respectively. Two patients in each group had both pelvic and distant recurrence. There was no correlation between tumor recurrence and type of operation. Median time interval from diagnosis to pelvic recurrence was 10 months in the S-group and 16 months in the RT-group. Postoperative complications in the form of wound sepsis were slightly more common in the RT-group. In summary, the applied treatment regimen, is well-tolerated and apparently does not affect the Dukes' stage of the tumor. Although there is no statistically significant difference, there is a trend of less pelvic recurrence in patients receiving preoperative radiotherapy.

Adenocarcinoma↗