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Biomedical subjects

A Howell

Publications and source records attributed to A Howell.

At least 217 records · Page 12Linked to original sources
PubMed1985

Preliminary report on use of depot formulation of LHRH analogue ICI 118630 (Zoladex) in patients with prostatic cancer.

A study was conducted of the response of the pituitary-testicular axis to two different methods of administration of the luteinising hormone releasing hormone (LHRH) analogue ICI 118630 (Zoladex) in patients with prostatic cancer. The analogue was given by continuous infusion to four previously untreated patients with prostatic cancer for 60 days (group 1). Subsequently a further four patients were given a depot formulation of the same analogue by subcutaneous injection once every 28 days (group 2). Both methods of administration produced similar, successful suppression of luteinising hormone (LH) associated with a reduction of testosterone to castrate concentrations. The median basal testosterone concentrations before treatment in groups 1 and 2 were 20.6 and 14.1 nmol/l (5.94 and 4.07 ng/ml) respectively; these were reduced to 1.4 and 1.1 nmol/l (0.40 and 0.32 ng/ml) within four weeks of the start of treatment. The median basal LH concentration in groups 1 and 2 were 7.9 and 16.6 IU/1 respectively, which were suppressed to 2.6 and 2.4 IU/1 by four weeks. The suppression of LH and testosterone was maintained with continuous subcutaneous infusion for up to 60 days in group 1, and by subsequent injections of the depot every 28 days in group 2. The use of depot preparation of an LHRH analogue to suppress gonadotrophin and sex hormone secretion offers the convenience of once monthly injections when LHRH analogues are required for the long term treatment of elderly patients with prostatic cancer and children with precocious puberty.

Aged↗
PubMed1985

Retroperitoneal tumour infiltration detected by bone scanning in patients with infiltrating lobular carcinoma of the breast.

Radionuclide bone scans performed in some patients with carcinoma of the breast showed abnormal retention of isotope in the renal pelvis which developed and progressed during the period of follow-up after mastectomy. This phenomenon was seen in 15 of 30 patients with infiltrating carcinoma of the breast (ILC) but in none of 29 with infiltrating duct carcinoma (IDC). Autopsies were performed in eight of the patients with ILC and three of those with IDC. Diffuse retroperitoneal and ureteric infiltration was seen in seven (88 per cent), with ILC and none with IDC. These data suggest that this scan abnormality is an indicator of retroperitoneal spread by ILC.

Bone Neoplasms↗
PubMed1985

Carcinomatous meningitis associated with infiltrating lobular carcinoma of the breast.

The records of 365 patients with advanced carcinoma of the breast were examined to identify those with CNS involvement. Nineteen (5.2%) developed parenchymal cerebral deposits and 10 (2.7%) developed meningeal infiltration during the course of their disease. Parenchymal cerebral deposits were almost exclusively associated with infiltrating duct carcinoma (95%) and meningeal infiltration (carcinomatous meningitis) was almost exclusively associated with infiltrating lobular carcinoma. Meningeal infiltration occurred late in the course of advanced disease and was associated with diffuse involvement of the bone marrow and abdominal structures.

Adult↗
PubMed1985

Activity of JM9 in advanced ovarian cancer: a phase I-II trial.

Thirty-nine patients with advanced solid tumors, including 28 with ovarian cancer, were entered in a phase I-II trial of a new platinum analog, JM9. Twenty-three patients had received prior chemotherapy which did not include cisplatin. Based on preliminary information from an ongoing study, our starting dose was 180 mg/m2. The total dose of JM9 was administered in 1 L of saline infused over 1 hour, with no additional hydration or electrolyte supplementation. Courses were repeated at 3-week intervals or after full recovery from thrombocytopenia. One hundred thirty-nine courses (range, one to six per patient) were administered at four dose levels: 180 mg/m2 (13 courses); 240 mg/m2 (64 courses); 300 mg/m2 (45 courses); and 350 mg/m2 (17 courses). The dose-limiting toxic effect was thrombocytopenia, which was dose-related and cumulative. Median platelet count nadirs were 50, 47, 25, and 28 X 10(9)/L for previously treated patients at dose levels of 180, 240, 300, and 350 mg/m2, respectively. For patients who had not received prior chemotherapy, the corresponding values were 403, 61, 44, and 36 X 10(9)/L. The nadir was predictable at Day 14 with recovery by Day 21 in earlier courses, but with delay of recovery to Days 28-42 in later courses and at higher dose levels. Twenty-five courses of chemotherapy in 15 patients were associated with a platelet count nadir of less than 20 X 10(9)/L, but despite this, serious hemorrhage was rare. Leukopenia was dose-related and mild; the median wbc count (X 10(9)/L) was 2.2 (range, 1.0-7.3) at the highest dose level of 350 mg/m2. The leukocyte count nadir was later than that for the platelet count (Days 21-28), and recovery was often not complete by the time of retreatment. All patients showed a progressive rise in mean corpuscular volume in successive courses, often accompanied by a fall in hemoglobin. Transfusions were required in 14 patients, 12 of whom had received prior chemotherapy. Nausea and vomiting, starting within 1 hour of drug administration, occurred in all patients, but appeared to be less severe and prolonged compared to that occurring with cisplatin. Diarrhea occurred in most patients at the two higher dose levels. There was no evidence of significant renal impairment, electrolyte disturbance, hearing loss, or peripheral neuropathy. Two patients had mild allergic reactions shortly after drug infusion and two others developed vasculitic rashes which were self-limiting.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1984

Controlled trial of adjuvant chemotherapy with cyclophosphamide, methotrexate, and fluorouracil for breast cancer.

327 patients with cancer of the breast and involvement of axillary lymph nodes were randomised, after total mastectomy and axillary clearance, to receive either no additional treatment or oral cyclophosphamide 80 mg/m2 on days 1-14, intravenous methotrexate 32 mg/m2 on days 1 and 8, and intravenous fluorouracil 480 mg/m2 on days 1 and 8 (CMF), which was repeated every 28 days for twelve cycles. There was a significantly longer relapse-free survival (RFS) in patients treated with CMF. A prolonged RFS was seen in premenopausal patients, those with 1-3 nodes involved, and those with 4 or more nodes involved, but a similar trend in postmenopausal patients failed to reach statistical significance. RFS was greater in patients with CMF-induced amenorrhoea than in controls and in treated patients whose primary tumour contained progesterone receptors. Dose of chemotherapy did not have a significant effect on RFS. Survival was not influenced by treatment.

Adult↗
PubMed1984

Steroid-hormone receptors and survival after first relapse in breast cancer.

Oestrogen receptors were measured in the primary breast tumours of 508 patients and progesterone receptors in those of 486 patients. Survival from mastectomy was significantly longer in patients with receptor-positive tumours. There was no significant difference between patients with receptor-positive and receptor-negative tumours in the relapse-free interval, but survival from first relapse was longer in patients with receptor-positive tumours. Axillary node status and tumour size indicated the probability of relapse but did not influence the length of survival after relapse. Response to tamoxifen or ovarian ablation was known in 65 of the 137 patients who relapsed. Survival from first relapse was significantly longer in patients who both responded to hormone therapy and had receptor-positive tumours. Patients who did not respond to hormone therapy and had receptor-positive tumours had the same survival characteristics as those with receptor-negative tumours who did not respond.

Breast Neoplasms↗
PubMed1984

The prognostic significance of two epithelial membrane antigens expressed by human mammary carcinomas.

As many patients with mammary carcinoma are now treated by conservative forms of surgery, there is a need for prognostic information obtainable from the primary tumour alone. One possible source is the antigenic profile of tumour cells. Using an indirect immunoperoxidase technique, we stained histological sections of the primary tumour from 175 patients with each of two monoclonal antibodies (HMFG-1, HMFG-2), raised against milk fat globule membrane antigens known to be preserved in formalin-fixed tissues. Sections were assessed by light microscopy as to both the overall distribution of antigen expressed and its site in tumour cells. The findings were related to relapse-free survival by life-table analysis. The median duration of follow-up was 36 months. Two patterns of staining with antibody HMFG-1 gave information of prognostic significance but staining with HMFG-2 was without significance. Complete absence of staining with HMFG-1 in 13 patients was associated with an extremely poor prognosis and 10 (77%) of these patients developed metastases within 18 months of follow-up (p less than 0.001). Extracellular staining (ECS) in 22 patients, however, was associated with a favourable prognosis. As assessed by a semi-quantitative method, only one patient (5%) demonstrating a high level of ECS developed metastases (p less than 0,004). These two patterns were analysed for a relationship to other prognostic indicators. Absence of staining was independent of histological grade, tumour size, axillary lymph node status and menopausal status. ECS was associated with low histological grade although this relationship was not absolute. In addition to their use in diagnosis, we conclude that monoclonal antibodies such as HMFG-1 may be useful as prognostic indicators.

Antibodies, Monoclonal↗
PubMed1984

The value of serial bone scanning in operable breast cancer.

The value of initial and serial isotope bone scans was assessed in 685 patients with operable primary breast cancer. Nineteen (2.8 per cent) patients had a positive initial scan and negative skeletal radiographs; only nine of these developed other evidence of metastatic disease after a mean follow up of 21 months. Five hundred and ten patients had serial scans up to five years after simple mastectomy; 51 (10 per cent) had scan conversion, of whom 37 developed clinical or radiological confirmation of recurrent disease at a mean follow-up of 13 months. Compared with clinical or radiological methods for the detection of first metastases serial bone scans gave a mean lead time of five months in 15 patients and no lead time in the remaining 22 patients. Twelve of forty-five patients with radiologically proven bone metastases had negative scans. Neither initial or serial bone scanning is clinically useful or economically viable as a routine screening or follow-up procedure for patients with operable breast cancer.

Adult↗
PubMed1984

A phase I toxicity study of human rDNA interferon in patients with solid tumours.

This study was designed to evaluate the clinical tolerance to multiple IM injections of rDNA-produced human alpha-2 interferon (IFN) (Schering-Plough 30500) in patients with solid tumours. IFN was administered in escalating IM doses in separate groups of patients daily for 14 days and then twice weekly for a further 10 weeks. The dosage levels were 1, 3, 10, and 30 million U/injection. Subjective toxicity could be divided into two types, acute and chronic. The acute reactions took the form of an influenza-like syndrome consisting in chills, rigors, headache, tremor, nausea, vomiting, and myalgia. These symptoms were dose-related but tachyphylaxis developed with continued dosing. The chronic toxicity consisted of malaise, lethargy, fatigue, anorexia, and confusion. These symptoms were not so dose-dependent and tended to become more severe with prolonged treatment. Objective toxicity consisted of myelosuppression and liver dysfunction. Granulocyte counts below 1.0 X 10(9)/l were seen in three patients at the 30-million-U level, with platelet counts less than 100 X 10(9)/l in two of these. Elevation of the liver enzymes were seen in all five patients treated at 30 million U, but returned to normal after 1 week without IFN in all but one patient. A tolerable dose (IM) for phase II/III studies lies between 3 and 10 million U for daily scheduling and between 10 and 30 million U for twice-weekly injections.

Blood↗
PubMed1984

Dibromodulcitol, mitomycin C and vinblastine (DMV) chemotherapy in advanced breast cancer.

A combination of dibromodulcitol 500 mg orally, mitomycin C 10 mg i.v. and vinblastine 10 mg i.v. all given on day 1 and repeated every 4 weeks was given to 40 patients with advanced breast cancer. All but one had received previous endocrine therapy. The response rate (CR + PR) in 24 previously untreated patients was 66% and was 37% in 16 previously treated patients. The survival of responders was significantly longer than non-responders. Thirty-two per cent of patients experienced nausea and vomiting. There was little myelosuppression or thrombocytopenia on the day of starting a new course of therapy but the haemoglobin dropped by 2 g/dl in 32% of patients during therapy. Thus DMV is a relatively non-toxic active regimen for patients with advanced breast cancer.

Adult↗
PubMed1984

A comparison of the metastatic pattern of infiltrating lobular carcinoma and infiltrating duct carcinoma of the breast.

The metastatic sites of infiltrating duct (IDC) and infiltrating lobular carcinoma (ILC) have been compared using both clinical and autopsy data. The following statistically significant differences were found: Lung parenchymal metastases were more common in IDC. Bone trephine biopsies were more likely to be positive in ILC. Carcinomatous meningitis was associated almost exclusively with ILC. Peritoneal/retroperitoneal metastases of distinctive pattern occurred in ILC. There was often associated linitis plastica-like involvement of the stomach wall and diffuse infiltration of the uterus. Hydronephrosis was a common secondary phenomenon.

Adult↗
PubMed1984

A comparison of three assays used for the in vitro chemosensitivity testing of human tumours.

In this study cell lines have been used to determine the level of correlation between three assays which are in use for in vitro prediction of human tumour chemosensitivity. The methods which were compared included a clonogenic assay, a monolayer assay and a short-term biochemical assay. The results indicated that the monolayer and clonogenic assays were either directly comparable or could be made comparable by reducing the drug exposure time in the monolayer assay. The biochemical assay also gave comparable results for 3 of the 5 drugs tested. It was concluded that although the 3 assays did not produce identical dose-response curves, the assays were equally valid when used for predictive testing because selection of cut-off points which were based on retrospective correlations between in vitro sensitivity data and response data, as established by other authors, compensated for differences in sensitivity between the assays.

Animals↗
PubMed1983

Treatment of advanced prostatic cancer with LHRH analogue ICI 118630: clinical response and hormonal mechanisms.

9 of 12 patients with advanced metastatic carcinoma of the prostate treated with luteinising-hormone-releasing-hormone (LHRH) analogue ICI 118630 for a mean period of 6 months showed objective evidence of response to treatment. Of 8 patients with bone pain, 7 obtained relief. After 6 weeks of treatment testosterone concentrations were reduced to castrate levels (range less than 2 to 5.5 nmol/l) from a pretreatment mean value of 15.7 nmol/l (range 10.3-24 nmol/l). Basal gonadotropin levels and gonadotropin responses to acute LHRH stimulation were suppressed within 2 weeks of treatment. However, the testosterone response to stimulation with human chorionic gonadotropin was unimpaired 4 weeks after the start of treatment. Therefore suppression of the basal testosterone concentration by ICI 118630 was due to inhibition of pituitary luteinising-hormone secretion rather than direct inhibition of testicular Leydig-cell function. ICI 118630 offers an alternative treatment to orchidectomy and oestrogen therapy.

Acid Phosphatase↗