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Biomedical subjects

A Goldhirsch

Publications and source records attributed to A Goldhirsch.

At least 253 records · Page 14Linked to original sources
PubMed1985

Adjuvant treatment in operable breast cancer.

The object of Ludwig III was to assess adjuvant therapy after total mastectomy and axillary clearance in postmenopausal women with breast cancer and axillary node metastases. Chemo-endocrine therapy (cyclophosphamide, methotrexate, 5-fluorouracil, prednisone and tamoxifen: CMFp + T) was compared with endocrine therapy (prednisone and tamoxifen: p + T) and with no adjuvant treatment in 463 evaluable patients aged 65 years or less. Treatment results are available (Ludwig Breast Cancer Study Group, Lancet i (1984) 1256-1260). Nodal status and receptor content of the primary were found to have prognostic value, while tumor size did not.

Aged↗
PubMed1985

A clinical trial of aminoglutethimide in advanced postmenopausal breast carcinoma: low response in patients previously treated with medroxyprogesterone.

In an attempt to define the influence of prior hormonal treatments upon aminoglutethimide activity in advanced cancer of the breast, 42 heavily pretreated postmenopausal patients received aminoglutethimide, 4 X 250 mg daily, with hydrocortisone or cortisone. Twenty-six received high doses of medroxyprogesterone before entering this study. There was no significant difference in patients' characteristics with or without medroxyprogesterone pretreatment. A comparison of patients with and without prior medroxyprogesterone shows a significant difference in the response rate to aminoglutethimide-hydrocortisone (4 vs 32%, P = 0.02). In patients pretreated with tamoxifen but not with medroxyprogesterone the response rate to aminoglutethimide was 36%. These results suggest that aminoglutethimide has a low activity in breast cancer patients previously exposed to medroxyprogesterone, an agent with glucocorticoid-like activity inducing adrenal suppression.

Adult↗
PubMed1985

Prognostic significance of peritumoral vessel invasion in clinical trials of adjuvant therapy for breast cancer with axillary lymph node metastasis.

To assess the prognostic significance of peritumoral vessel invasion, data were examined for 1,510 women entered into the Ludwig Breast Cancer Group Trials I to IV evaluating adjuvant therapy for operable breast cancer with axillary nodal metastasis. Vessel invasion by tumor cells was identified by routine light microscopy in 59 per cent (889 of 1,510) of the patients and was equally distributed between premenopausal/perimenopausal (60 per cent, 468 of 778) and postmenopausal (58 per cent, 421 of 732) women. In logrank analyses stratified by nodal status (one to three or four or more positive nodes), the four-year disease-free survival (DFS) rate was significantly lower in patients with vessel invasion than in women without vessel invasion (50 per cent versus 65 per cent, P less than 0.0001). This DFS difference was seen for both premenopausal/perimenopausal (P = 0.0004) and postmenopausal (P = 0.0002) patients. The four-year overall survival rate was also lower in patients with vessel invasion (71 per cent versus 82 per cent, P = 0.0006), both for premenopausal/perimenopausal (P = 0.002) and postmenopausal (P = 0.04) women. The presence of vessel invasion was significantly associated with increasing numbers of positive axillary lymph nodes, rising tumor grade, nonstellate tumor border growth pattern, and higher steroid hormone receptor content of the primary tumor. The assessment of peritumoral vessel invasion continued to have prognostic significance for DFS (P less than 0.0001) and overall survival (P = 0.003) when evaluated in multivariate models controlling for treatment assigned, nodal status, tumor size, estrogen receptor status, menopausal status, and age. Depending on the subpopulation, patients with vessel invasion had a 41 per cent to 54 per cent greater risk of treatment failure than those without vessel invasion and a 29 per cent to 64 per cent greater risk of death. The percentage of treatment failures at distant sites was higher for women with than for those without vessel invasion (27 per cent versus 18 per cent, P = 0.003). In patients with axillary lymph node metastases, peritumoral vessel invasion may be a sign of increased systemic disease burden.

Aged↗
PubMed1985

[Chemotherapy as primary therapy in non-radically operated ovarian cancer].

Forthwith the results of chemotherapy on advanced ovarian carcinoma are summarized. The following conclusions can be drawn: stages Ia and Ib of low malignancy degrees should receive follow-up treatment. Stages II and I of high malignancy degrees should receive radiotherapy to the whole abdomen. The value of intensive chemotherapy is examined. Stage II with residual tumor should undergo combined cis-platin treatment for 4 to 6 months. Stage III with residual tumor should receive intensive chemotherapy followed by a second-look operation and radiotherapy to the whole abdomen. The prognosis of cases with large residual tumors is very unfavorable so that the value of radical therapy must be further investigated.

Antineoplastic Agents↗
PubMed1985

[Total abdominal irradiation following combination chemotherapy and second-look laparotomy in the treatment of advanced ovarian cancer].

From 1980 to 1984 fifty-four patients with advanced ovarian carcinoma after operation and concluding chemotherapy with alkeran (n = 7) or cis-platin/alkeran +/- hexamethylmelamine (n = 47) as well as second-look laparotomy received follow-up radiotherapy either with the moving-strip technique (n = 35) or later the open-field technique (n = 19). 32 patients in CR received radiation therapy. 15 patients in CR are without relapse after undergoing open-field radiation therapy and a mean observation period of 25 months. At this point of time 5 of 17 patients had relapses under the moving-strip radiation treatment. The frequency of the relapses is apparently due to the very long periods of radiation and numerous interruptions in treatment. If residual tumors were present at the begin of ray therapy, a CR could only be achieved in cases where the previous monotherapy was with alkeran.

Adenocarcinoma↗
PubMed1985

The treatment of ovarian cancer by a multimodality approach: remission induction with chemotherapy--hexa PAMP and PAMP regimens--followed by whole-abdominal radiation.

Seventy-six evaluable patients with ovarian carcinoma stages FIGO IIb, IIc, III, and IV, either received cis-platin (P) (80 mg/m2 iv. day 1), melphalan (PAM) (12 mg/m2 i.v. day 2) and hexamethylmelamine (HEXAPAMP) (135 mg/m2 orally days 8 to 21) or the same dose of cis-platin and melphalan but no hexamethylmelamine (PAMP) every four weeks. In 24 patients (32%) a surgically ascertained CR was achieved. 16 of these received follow-up radiation treatment to the whole abdomen. At present 19 patients are without relapse (average time 24 months). The trial has not been concluded. Particularly no predictions can be made on the value of follow-up radiation therapy in obtaining long-term remission rates.

Adult↗
PubMed1985

Subcapsular liver metastasis in ovarian cancer. Computed tomography and surgical staging.

In 38 patients with surgically-staged ovarian carcinoma, the role of CT scan in diagnosis of subcapsular liver metastases as well as its importance in determining the stage of ovarian carcinoma were investigated. Assessment of the perihepatic space was not possible intraoperatively in 14% of the cases because of tumourous adhesions. Subcapuslar metastases were revealed by CT scan in five (20%) patients whose livers were found normal during surgery (24 patients). In two of these (8%) the surgically-determined stage IIc had to be converted to stage III. These findings make a case for a more thorough visual examination of the dorsal surface of the liver during the staging process.

Adenocarcinoma↗
PubMed1984

A phase I trial of cis-diammine-1,1-cyclobutane dicarboxylate platinum II (Carboplatin, CBDCA, JM-8) with a single dose every five week-schedule.

Carboplatin, a new platinum analogue, was administered intravenously on a schedule of a single dose every five weeks to 23 patients with advanced malignant solid tumors. Patients were treated at six dosage levels ranging from 200-550 mg/m2 every five weeks. Thrombocytopenia was dose-limiting. At 550 mg/m2 Carboplatin, the median platelet nadir was 65 000/mm3. Leukopenia was common, but usually of mild to moderate degree. Gastrointestinal upset was commonly seen at all dose levels, but 35% of the patients experienced no vomiting. No significant increase of the serum creatinine following Carboplatin was seen. In 16 patients serial determinations of the creatinine clearance were performed. The median base line creatinine clearance was 87 (50-155) ml/min and dropped to a median lowest creatinine clearance of 69 (23-171) ml/min on day four (p less than 0.05). The median creatinine clearance before the next Carboplatin treatment was 89 (42-155) ml/min. No significant proteinuria or electrolyte disturbances were noted. Carboplatin exhibited antitumor activity in ovarian, endometrial, thyroid and gastric carcinomas. The maximally tolerated dose appears to be 550 mg/m2 every five weeks. A starting dose of 450 mg/m2 seems to be appropriate for Phase II studies. In patients with impaired renal function and/or prior cis-Platin chemotherapy, Carboplatin at doses of 200-500 mg/m2 induced renal and severe hematological toxicity.

Adult↗
PubMed1984

Whole-abdomen radiation in patients with advanced ovarian carcinoma after surgery, chemotherapy, and second-look laparotomy.

Forty-three patients with ovarian carcinoma were treated with whole-abdomen radiation (moving strip +/- pelvic radiation), 15 patients had not received prior chemotherapy, and 28 patients were irradiated following chemotherapy and second-look laparotomy. Ten of these had been treated with a variety of chemotherapy regimens (L-PAM, CHAD, Hexa-CAF). Eighteen patients were treated in an ongoing prospective trial with combination chemotherapy consisting of melphalan, cis-platinum, and hexamethylmelamine++ (HexaPAMP). Thrombocytopenia was the limiting toxicity. A temporary pause in the radiation schedule allowing platelets to recover made it possible to complete treatment in 80% of the patients. The acute toxic effects, which included the expected side effects of radiation therapy on intestine, liver and lung, were not more frequent or more severe in the patients who had received prior chemotherapy than in those who had radiation therapy alone. Thirty-four of 43 patients (stage I, seven patients; stage II, seven patients; stage III, 27 patients; stage IV, two patients) are alive and without evidence of disease 26 + months (range 7 to 64 months) after entering the postsurgical treatment program.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Pathologic data of prognostic significance for remission induction in advanced ovarian carcinoma.

Sixty-eight patients with "advanced ovarian carcinoma" were entered into an ongoing phase-II trial for remission induction with cis-platinum (DDP) 80 mg/m2 i.v. on day 1 followed by forced saline diuresis, melphalan (L-PAM) 12 mg/m2 i.v. on day 2 and hexamethylmelamine (HMM) 130 mg/m2 p.o. X 14 days from days 8-21 in six monthly cycles following operative resection and/or staging. Fifty-one patients were evaluable for response, ten had not completed six courses and could not be assessed, two patients died early (one probably of toxicity), and five patients refused treatment and follow-up. Thirty-Two patients had serous, endometrioid or undifferentiated carcinomas of the ovary. Of these, 11 (35%) achieved a pathologically proven complete remission (CR), five (16%) were NED after second-look (residual disease in ovary or removed omentum with all other biopsies and cytology washings negative), eight (32%) achieved a partial remission (PR), and three (12%) had progressive disease. None of the seven patients with clear-cell carcinoma and none of the three patients with Mullerian tumor of the ovary responded. Six of nine patients with tumors of uncertain origin or proven metastasis to ovary did not respond to treatment. These preliminary results indicate that advanced ovarian carcinomas form a heterogeneous group of recognizable neoplastic diseases with striking variation in response to treatment.

Adenocarcinoma↗
PubMed1984

Receptor heterogeneity of human breast cancer as measured by multiple intratumoral assays of estrogen and progesterone receptor.

Multiple intratumoral tissue samples from the primary mass of 30 consecutive invasive breast cancer patients were assayed for estrogen receptor (ER) and progesterone receptor (PR) by the dextran-coated charcoal method following frozen section histopathological examination. Steroid receptor status of each sample was classified as positive (R+) or negative (R-), based only upon quantitative guide lines from the ER/PR results. Four out of 32 (12.5%) of the invasive cancers had an intratumoral sample classified as R+ and one sample as R-. R+ invasive ductal carcinomas has a highly significant degree of tubule formation (P = 0.005) when compared with R- invasive ductal cancers. While the quantitative ER content (r = 0.18) and the degree of quantitative variation in ER content (P = 0.04) did not correlate with the tumor cellularity of the individual samples, tumor cellularity (P = 0.005) and ER content (P = 0.005) were lower in the samples from the tumor border than from the central tumor samples. Variations in ER and PR content may be found on a regional basis within a breast tumor mass resulting from heterogeneity of tumor subpopulations and/or differences in tumor cellularity.

Adult↗
PubMed1984

[Intratumoral regional differences in hormone receptor status of breast cancer].

Biopsy specimens of tissue were taken from 32 invasive carcinomas of the breast, in each case from the centre of the tumour, the tumour margin and the surrounding mammary gland tissue. After preparation of a frozen section for tissue identification, the concentration of oestrogen and progesteron receptors (ER and PR, respectively) was determined in each specimen by means of the dextrane-coated charcoal method. On the basis of these measured values, the receptor status of each specimen was classified either as positive (R+), borderline value (BL) or as negative (R-). Various morphological parameters were compared with the measured data. 9 (28%) of the 32 carcinomas demonstrated such high intratumoural differences in receptor concentration that the receptor status was classified quite differently in each of them. Formation of tubuli of the invasive ductal carcinomas was more marked with the R+ tumours (p = 0.005) than with the R- tumours. The quantitative ER content did not correlate with the abundance of the tissue specimen (r = 0.182). The regional differences in receptor status could not be explained, neither by the abundance in cells nor by morphological peculiarities of the tumour. - It follows from the results of this study that intratumoural regional variations in ER and PR concentrations can occur in carcinoma of the breast, and that such variations can have clinical significance.

Breast Neoplasms↗
PubMed1984

[Computed tomography, primary laparotomy and second look surgery in ovarian carcinoma].

The value of computed tomography for staging and for observing the course of ovarian carcinomas was analysed in 56 patients in whom the diagnosis had been verified by laparotomy. Ct achieved correct staging in 85% of cases. The ability of CT to demonstrate a variety of abnormalities varies; ascites and pleural effusions were shown in 100%, lymph node metastases in 90%, infiltration of the recto-sigmoid and terminal ileum in 70-80%, sub-capsular liver metastases in 70%, involvement of the omentum in 70%, of the peritoneum in 65% and of the mesentery in 35%. A 'second-look' operation remains necessary in order to confirm complete remission after chemotherapy, since CT is only rarely able to show residual tumours smaller than 1 1/2-2 cm.

Adenocarcinoma↗
PubMed1984

[Value of computed tomography for the assessment of lymph node metastases in ovarian cancer].

The value of CT for demonstrating iliac and retroperitoneal lymph nodes involved by ovarian carcinoma was examined following primary or secondary laparotomy in 62 patients. CT had an accuracy of 74%, sensitivity of 80%, a specificity of 67%; there were false negatives in 20% and false positives in 33%. Local tumours of grade I and II, with no evidence of retroperitoneal metastases and normal palpation, must have intra-operative lymph node biopsies in order to exclude micrometastases. Under these circumstances, pre-operative lymphography need not be carried out.

Adult↗
PubMed1984

Immunohistochemical localization of galactosyltransferase in the normal human ovary and fallopian tube.

Galactosyltransferase (UDP-galactose: 2-acetamido-2-deoxy beta-D-glucopyranose beta-(1-4) transferase) in human tissue specimens from ovaries and the corresponding fallopian tubes was localized immunohistochemically for light microscopy. An affinity-purified rabbit anti-human milk galactosyltransferase antibody was used. Intracellular galactosyltransferase was found to be localized to the juxtanuclear (Golgi) region of the secretory cells of the fallopian-tube epithelium and to the ovarian stromal cells involved in steroid-hormone production. Cell-surface galactosyltransferase was localized to ciliated cells of the fallopian-tube epithelium. During the follicular phase of the menstrual cycle, galactosyltransferase was found only in the Golgi regions of theca interna cells of the ovarian graafian follicle, and in the fallopian tube was found predominantly on the cilia of epithelial cells. During the luteal phase, galactosyltransferase was abundant in the Golgi regions of granulosa lutein cells of the corpus luteum, and was predominant in the secretory cells of the tubal epithelium. Galactosyltransferase was not detected on the mesothelial ovarian surface. The results demonstrate that the cellular distribution and location of galactosyltransferase correlates with phenotypic differentiation and varies during the human female hormonal cycle.

Adolescent↗