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Biomedical subjects

A Goldhirsch

Publications and source records attributed to A Goldhirsch.

At least 271 records · Page 15Linked to original sources
PubMed1984

Randomized trial of low- versus high-dose medroxyprogesterone acetate in the induction treatment of postmenopausal patients with advanced breast cancer.

In a randomized trial, 210 postmenopausal women with advanced measurable breast cancer were allocated to two different schedules of medroxyprogesterone acetate (MPA). In the induction phase they received either 1,000 mg intramuscular (IM) MPA (high dose) daily or 500 mg IM MPA (low dose) twice weekly for four weeks. The maintenance treatment consisted of 500 mg MPA IM once weekly for all patients. In total, 184 patients were considered evaluable. The response rate was significantly higher (p = 0.004) for patients receiving high-dose MPA (30 [33%] of 91) as compared to the women receiving the low-dose regimen (14 [15%] of 93) and was consistent across all prognostic subgroups. These prognostic subgroups included soft-tissue and osseous metastases, two metastatic sites, patients greater than 60 years, disease-free interval greater than 60 months, no prior chemotherapy, patients with a response to the last hormonal treatment before MPA, unknown estrogen receptors, and positive progestin receptors. The two different schedules of MPA did not influence the time to progression and the survival. Toxicity was similar in both regimens. These results confirm that a higher response rate can be achieved with a more intensive MPA schedule. This treatment may represent an ideal second-line choice in the endocrine therapy of advanced breast cancer; however, its role as a first-line treatment remains to be defined.

Age Factors↗
PubMed1984

Combination chemotherapy for non-small cell lung cancer with doxorubicin and mitomycin or cisplatin and etoposide.

The combinations of doxorubicin (40 mg/m2 iv every 3 weeks) and mitomycin (12 mg/m2 iv every 6 weeks) or cisplatin (80 mg/m2 iv every 3 weeks X 3, then every 6 weeks) and etoposide (80 mg/m2 iv on Days 1-3 every 3 weeks X 3, then every 6 weeks) were evaluated in a randomized phase II trial in 77 patients with measurable or evaluable non-small cell lung cancer. No patient had been pretreated with prior chemotherapy. The overall response rate for the doxorubicin and mitomycin regimen was 11% and for the cisplatin and etoposide regimen was 23%. Responses lasted a median of 5.5 months. Median survival was 7.0 months for the doxorubicin and mitomycin regimen and 8.0 months for the cisplatin and etoposide regimen. One treatment-related death was observed after doxorubicin and mitomycin in a patient who had received radiation therapy immediately prior to study entry. Otherwise, the hematologic toxicity of both chemotherapy regimens was moderate, with only six patients (10%) having World Health Organization grade 3 toxicity and no patients having World Health Organization grade 4 toxicity. However, subjective tolerance gastrointestinal upset) of the cisplatin and etoposide combination was poor.

Adenocarcinoma↗
PubMed1983

[Ultrasonic diagnosis of ovarian carcinoma].

Gray-scale ultrasonography was performed prior to surgery in 68 patients with tumors of the ovary. Thirty-four of the 38 benign tumors were considered benign by sonographic criteria. Three of 4 borderline epithelial tumors were considered malignant sonographically, as were 22 of the 26 cancers of the ovary (sensitivity 84%). Nineteen of them were malignant epithelial neoplasms and most were classified as FIGO stages III and IV (76%). In 6 of the 7 patients with stage I and II cancers the latter were considered malignant by sonographic criteria. Twenty-three of the 26 cancers were classified as having a complex structure using the classic ultrasonographic criteria. Histopathological evaluation did not correlate with the ultrasonic findings: sonography could not predict the correct stage and a particular histological type. Nevertheless, ultrasonography is a valuable diagnostic tool as a preoperative procedure in patients with a suspected ovarian neoplasm.

Adolescent↗
PubMed1983

[High-dosage methylprednisolone as an antiemetic in cytostatic-induced vomiting].

The antiemetic efficacy of 375 mg methylprednisolone given as slow i.v. push injection was assessed in 27 tumor patients receiving strongly emetic cytostatic treatment. 13 of 27 patients were partially or completely protected from nausea and vomiting. Only minor side effects from methylprednisolone were observed: two patients complained of increased fatigue and four patients experienced facial rash with swelling 1 to 24 hours after the injection of methylprednisolone. High-dose methylprednisolone is an effective antiemetic treatment for patients receiving cancer chemotherapy.

Adult↗
PubMed1983

Estrogen and progesterone receptors in meningiomas in relation to clinical and pathologic features.

Tumor estradiol and progesterone binding sites were studied in 34 patients with meningioma. Twenty of the meningiomas contained very low titers (mean, 45 fmol/g of tumor; range, 0-201 fmol/g of tumor) of a nonspecific cytoplasmic [3H]estradiol binding component, whereas 26 of the tumors contained high titers of specific high-affinity cytosol [3H]promegestone (R5020; progesterone) binding sites (mean, 1476 fmol/g of tumor; range, 0-8328 fmol/g of tumor). No nuclear binding activity for [3H]estradiol could be detected in 12 of the 34 meningiomas studied, irrespective of the progesterone binding activity. There was no correlation between high progesterone binding activity and the age or the sex of the patient, nor between tumor location and cellular mitotic index. However, progesterone binding activity was present more frequently in meningothelial (95%, 18/21 patients) than in transitional (55%, 5/9 patients) or fibroplastic (25%, 1/4 patients) tumor histologic types. These data suggest that the cellular biosynthesis of the progesterone binding component in meningiomas is not estrogen regulated as it is in other classic estrogen target tissues, such as the breast.

Adolescent↗
PubMed1983

Estrogen receptor in malignant melanoma: fact or artefact?

A model system is presented to explain how tyrosinase, an enzyme unique to pigmented cells such as normal and malignant melanocytes can oxidize [3H]-estradiol to radiolabeled products which closely resemble the tight binding of [3H]-estradiol to estrogen receptor. In the model system studied, tyrosinase oxidized [2,4,6,7-3H]-estradiol to [3H]-water and [3H]-estradiol metabolites, the latter of which formed ring-substituted conjugates with nucleophiles like monothioglycerol and BSA. Radiolabeled estradiol without tritium in the C-2 position (i.e. [6,7-3H]-estradiol) failed to liberate [3H]-water when exposed to tyrosinase but, nevertheless, did form ring-substituted [3H]-estradiol adducts with nucleophiles. The [3H]-water and the ring-substituted radiolabeled products possessed several characteristics of a genuine estrogen receptor protein in that they were resistant to dextran-coated charcoal (DCC) adsorption and their enzymatic formation was inhibited with non-steroidal estrogens like diethylstilbestrol. Other natural (estradiol) and synthetic (hydroxytamoxifen) estrogens which contain the phenol grouping also inhibited the enzymatic oxidation of [3H]-estradiol. Although it was difficult to differentiate estrogen receptor from tyrosinase using the conventional DCC assay system, several differences in these two proteins permitted a distinction to be made between them. First, tyrosinase oxidation of [3H]-estradiol was markedly inhibited by sulfhydryl reducing agents (monothioglycerol) that stabilize [3H]-estradiol binding to estrogen receptor. Second, estrogen receptor adsorbed by hydroxylapatite whereas tyrosinase did not, thus permitting the separation of these two proteins prior to incubation with [3H]-estradiol. We conclude that the [3H]-estradiol binding components in melanoma previously reported to be estrogen receptor probably represent instead the radiolabeled products of the tyrosinase-catalyzed oxidation of [3H]-estradiol.

Breast Neoplasms↗
PubMed1983

Randomized trial of 3 different regimens of combination chemotherapy in patients receiving simultaneously a hormonal treatment for advanced breast cancer.

We report the results of a randomized trial carried out by the Swiss Group for Clinical Cancer Research (SAKK) and in which 230 patients with advanced breast cancer receiving concurrently a hormonal treatment (oophorectomy for pre- and tamoxifen for postmenopausal women) were randomly allocated to three different regimens of combination chemotherapy. The therapeutic results registered with the two more intensive combinations (LMP/FVP and LMFP/ADM) were similar with regard to response rates, time to progression and survival. The patients receiving the low-dose chemotherapy lmfp showed a statistically significant lower response rate (32%, P less than 0.001) and a shorter survival (P = 0.03) than the results observed in patients treated with the two other regimens. This difference was particularly pronounced, at least regarding survival, in the following subgroups: postmenopausal women, patients with a poor performance status, dominant visceral lesions, two sites of disease and a disease-free interval longer than 12 months. Patients with bony metastases as dominant lesion fared similarly with all three regimens of chemotherapy. This latter subset of advanced breast cancer patients should probably be spared too intensive cytotoxic treatment. This is, to our knowledge, the first report of a randomized trial showing an evident correlation between response rate and survival in various subgroups of patients with advanced breast cancer treated with different chemotherapeutic regimens.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1983

A phase I trial of marcellomycin with a weekly dose schedule.

Marcellomycin, a new anthracycline antibiotic, was administered intravenously on a weekly schedule to 22 patients with advanced malignant solid tumors. Patients were treated at 6 dosage levels ranging from 5 to 30 mg/m2 weekly for 4 weeks. Courses were repeated after a 3-week rest period. Hematologic toxicity was dose-limiting but unpredictable. Of 10 patients treated with weekly doses of 27.5 mg/m2, 3 patients exhibited myelosuppression and 2 died in agranulocytosis. Moderate to severe nausea and vomiting occurred in 19 of 22 evaluable patients. Other toxic effects were non-acute and consisted of mild stomatitis, diarrhea, phlebitis and moderate fatigue in 1-3 patients each. In 17 patients evaluable for antitumor activity no partial or complete responses occurred. One patient with advanced breast cancer showed a mixed response. Marcellomycin given on a weekly dose schedule has unpredictable and erratic hematologic toxicity. The maximally tolerated dose appears to be between 27.5 and 30 mg/m2 weekly. However, no firm recommendations can be given for a dose level that results in tolerable, predictable and reversible toxicity.

Adult↗
PubMed1983

Acute cerebrovascular accident after treatment with cis-platinum and methylprednisolone.

A 53-year-old woman with recurrent ovarian cancer sustained an intracerebral hemorrhage after the 4th course of a chemotherapy regimen which included cis-platinum (DDP). She received high-dose methylprednisolone as an antiemetic along with the DDP. No metastases or abnormal vascularity were found on histological examination of the right frontal lobe which had been removed surgically. Causes of cerebrovascular accidents during and following chemotherapy are discussed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1983

An enzyme-linked immunosorbent assay for lactose synthase (galactosyltransferase) in serum and its application as a tumor marker in ovarian carcinoma.

This assay for lactose synthase (galactosyltransferase, EC 2.4.1.22) in serum involves two sequential incubations: serially diluted standard or sample antigen is reacted with a fixed amount of antibody; unbound antibody is then adsorbed to wells of antigen-coated microtiter plates and determined by a second antibody directed against the first antibody and coupled to phosphatase. The standard curve is linear for galactosyltransferase concentrations of 10 to 600 micrograms/L. The within-assay CV of a serum sample was 9.3% (SD 4.1%), the between-assay was 3.8% (SD 2.4%). Serum galactosyltransferase concentrations computed from three different dilutions yielded CVs of 6.5% (SD 5.7%, n = 14). We evaluated the method's accuracy by recovery analysis and by comparing enzyme activity in serum with that of purified galactosyltransferase from human milk. The normal reference interval, as estimated from data on 27 healthy blood donors, was 60-436 micrograms/L (mean 224, SD 101 micrograms/L). We applied the assay to samples of serum from ovarian carcinoma patients grouped according to tumor burden. We also determined galactosyltransferase in ascites fluid and found these values useful for diagnosis, whereas determinations in serum may serve mainly for patient monitoring.

Ascitic Fluid↗
PubMed1983

Computed tomography prior to second-look operation in advanced ovarian cancer.

Twenty-six patients treated with chemotherapy for ovarian cancer underwent a second-look laparotomy after clinical response (or in the absence of evidence of progressive disease). Abdominopelvic computed tomography (CT) was performed before this operation. Five patients (19%) who had been demonstrated as being free of disease by computed tomography were found to have a tumor larger than 1 cm. Computed tomography sensitivity was good in detection of lymph node metastases (83%), average for pelvic residual tumor (63%) and the omentum (50%), and low for other peritoneal locations (11%). Before second-look operation, the computed tomography scan provides useful surgical information about residual disease in retroperitoneal lymph nodes. However, negative computed tomography findings do not exclude residual tumor or confirm complete remission and therefore cannot replace the second-look laparotomy at this time.

Female↗