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Biomedical subjects

A Coates

Publications and source records attributed to A Coates.

At least 91 records · Page 5Linked to original sources
PubMed1987

Mitomycin and mitoxantrone in previously treated patients with advanced breast cancer.

A total of 56 heavily pretreated patients with advanced breast cancer were treated with the combination mitomycin and mitoxantrone. Partial responses were seen in ten of 56 patients (18%), or ten of 44 (23%) completing two courses, while 18 (32%) had stable disease. Responses were seen in eight patients failing doxorubicin. The median duration of response was 26 weeks, with responders surviving a median of 37 weeks. A total of 59% of the courses were associated with World Health Organization grade 3 or 4 neutropenia (less than 1.0 X 10(9) cells/L). Nausea and vomiting were minimal. Mitomycin and mitoxantrone has activity in heavily pretreated patients with advanced breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Phase I study of epirubicin given on a weekly schedule.

Epirubicin was studied in a phase I setting to find the maximum tolerated dose when given weekly for 3 of 4 weeks. Forty-one evaluable patients were treated in groups at doses increasing from 20 to 45 mg/m2. The highest dose level produced the maximum degree of myelosuppression (lowest neutrophil count, 1.9 X 10(9)/L; range, 0-3.7) recorded on Day 22. This was well-tolerated in this group of mainly pretreated patients. Nonhematologic side effects were minimal. This dose schedule allows a greater dose per unit time to be administered than other recommended schedules for epirubicin.

Adult↗
PubMed1986

Globin gene transcripts can utilize histone gene 3' end processing signals.

Deletion of the poly(A) site from the human alpha globin gene results in a defective gene that produces very little stable mRNA as compared to the intact gene, presumably due to the instability of the mRNA. However, if the Alpha poly(A) site is replaced by mouse histone H4 3' end processing signals, significant levels of hybrid alpha/H4 mRNA are obtained and the transcripts formed are cytoplasmic and poly(A)-. When both mouse histone 3' end processing signals and the alpha globin poly(A) site signals are placed in tandem after the alpha globin gene promoter and coding sequence, the alpha poly(A) site signals are utilized exclusively. These results show that the histone 3' end processing signals can function independently of the histone promoter and the transcripts which are normally polyadenylated (alpha globin) can be stabilized by a poly(A)- histone mRNA 3' terminus. Furthermore, these results show that the histone 3' end processing signals are less efficient than the alpha globin poly(A) site signals, if the two are placed in direct competition.

Animals↗
PubMed1986

Immunological effects of recombinant interferon alfa-2a in patients with disseminated melanoma.

Twenty patients with disseminated melanoma were treated with interferon alfa-2a, given by intramuscular (IM) injection three times a week in escalating doses from 15 to 50 X 10(6) U/m2. Of 18 patients considered evaluable, two had complete remission and in two others the disease was stabilized. Laboratory tests 6 hours after injection of interferon alfa-2a indicated a marked lymphopenia and a reduction in natural killer (NK) cell activity. Sequential changes (measured before injection of interferon alfa-2a on days 3, 10, and 31) consisted of neutropenia, thrombocytopenia, and a slight increase in OKT4 positive T cells compared with OKT8 positive T cells. NK activity against the K562 target cells was increased in most patients during the first week of treatment, returning to near or below pretreatment levels thereafter. This response contrasted with a delayed increase against melanoma target cells in 10 patients. The latter correlated with an increase in mitogen-stimulated interleukin-2 (IL2) production, and may indicate that the cytotoxic activity resulted from lymphokine-activated killer (LAK) cells. Changes in cortisol levels may explain some effects on the immune system, such as depression of IL2 and immunoglobulin production in vitro, and the differences noted in clinical responses during the present study compared with those observed with interferon alfa-2b given by intravenous (IV) injection in 5-day cycles. These results suggest that interferon alfa-2a has antitumor activity in certain melanoma patients, in particular those with metastases to pulmonary or subcutaneous sites. Assays of IL2 production and LAK activity may assist in the selection of patients who respond to interferon alfa-2a and help to optimize treatment regimens.

Adult↗
PubMed1986

Phase I and pharmacokinetic study of tiazofurin (NSC 286193) administered by 5-day continuous infusion.

A phase I and pharmacokinetic study of tiazofurin (NSC 286193), a C-nucleoside that inhibits IMP dehydrogenase, has been completed. The drug was administered by continuous infusion over 5 days. The maximum tolerated dose was 1650 mg/m2 per day, neurological toxicity being the dose-limiting factor. Gastrointestinal and hematological toxicity were mild. A definite relationship exists between dosage and steady-state levels. The plasma clearance was 29.13 (+/- SD 4.05) ml/min per m2. No complete or partial remissions were demonstrated among the 18 patients treated at five dose levels between 550 mg/m2 and 2200 mg/m2 per day.

Adult↗
PubMed1986

Phase-II study of recombinant alpha 2-interferon in advanced malignant melanoma.

Fifteen patients with metastatic malignant melanoma, including 10 who had not previously received systemic therapy, were treated with recombinant alpha2-interferon (IFN-alpha 2) in a dose of 20 million IU/m2 by 30-min i.v. infusion daily for 5 days each 14 days. Evaluable metastatic sites included lung, subcutaneous tissue, liver, nodes, adrenals, and bone. Subjective toxicity was generally mild to moderate, with fever (38.2-40.2 degrees C), occasional rigors, fatigue, myalgia, headache, and nausea. Objective toxicity included transient neutropenia and elevation of hepatic enzymes, particularly gamma-glutamyl transpeptidase. In 1 of the 10 patients receiving more than one cycle, IFN dosage was reduced because of toxicity, but later reescalated. All patients were evaluated for response. No overall partial or complete responses were observed, but two site responses (lung and subcutaneous tissue) were seen. Median survival from start of IFN treatment was 19 weeks. High doses of IFN were reasonably well tolerated in this study, but the results suggest little activity against malignant melanoma.

Adrenal Gland Neoplasms↗
PubMed1986

Comparative study on the effects of recombinant alpha-2 interferon on immune function in patients with disseminated melanoma.

Fifteen patients with disseminated melanoma were treated by intravenous administration of recombinant alpha-2 interferon (rIFN-alpha 2) on 5 consecutive days every 2 weeks. Immunological studies on approximately 50% of the patients revealed no significant changes in lymphocyte numbers or T-cell subsets. Natural killer (NK) activity against the K562 target cell and a melanoma cell was increased in the first treatment cycle, but in subsequent treatment cycles it tended to decrease against the melanoma cell and to show either no change or moderate increases against the K562 target cell. Interleukin-2 (IL-2) production from mitogen-stimulated lymphocytes was decreased in most patients in each treatment cycle. This also applied to immunoglobulin production in vitro from pokeweed mitogen (PWM)-stimulated B and T cells. The latter was not due to the induction of radiation-sensitive suppressor T cells and may reflect effects on B cells or helper T cells. The repeated inhibition of IL-2 production with each cycle of treatment and the decrease in NK activity against the melanoma target cells after the first treatment cycle contrasted with the return to at or above pretreatment values of these tests when rIFN-alpha A was given intramuscularly on an alternate-day basis. It is suggested that these effects may be due to the relatively greater increase in endogenous cortisol production at the beginning of each treatment cycle in patients given rIFN-alpha 2 intravenously compared to that observed in patients treated with rIFN-alpha A on alternate days intramuscularly. Immunosuppression resulting from the increase in cortisol production may be one of the factors accounting for the low tumor response rate of patients in this study and may emphasize the possible importance of the schedule of rIFN-alpha administration for obtaining optimal antitumor responses.

Adult↗
PubMed1984

Advanced breast cancer: response to high dose oral medroxyprogesterone acetate.

We treated 105 patients with advanced breast cancer, using the progestational agent medroxyprogesterone acetate (MPA), 200 mg orally tds in a non-randomised trial. In general they were a poor risk population, since 78 had received prior endocrine therapy (21 more than one type) and 58 prior chemotherapy. Treatment was well tolerated. Side effects included weight gain, muscle cramps, fine tremor and fluid retention, but these were usually mild, resolved if the dose of drug was reduced, and only one patient stopped treatment because of toxicity. Seventeen patients died within six weeks of starting MPA, and disease progression occurred in a further 58. Nine have had stable disease for periods ranging from two to 11 months, and there were 21 who showed disease regression. Response to treatment continues in 13 of these patients, and at the time of writing the median duration of response is 10 months. Response rates were similar in pre- and post-menopausal patients. The dose of MPA was double to 400 mg tds in 16 patients whose disease had progressed on 200 mg tds, but no additional responses were seen in this group. Seven out of 24 (29%) patients who had not received prior endocrine therapy responded to high dose oral MPA, a response rate similar to that seen following other hormonal manipulations, but because the drug also has activity against hormone-resistant tumours and is well tolerated, it should have role in the treatment of advanced breast cancer.

Antineoplastic Agents↗
PubMed1983

On the receiving end--II. Linear analogue self-assessment (LASA) in evaluation of aspects of the quality of life of cancer patients receiving therapy.

Linear analogue self-assessment (LASA) scales were used to measure general well-being and specific factors (mood, pain, nausea and vomiting, appetite, breathlessness, physical activity) in patients receiving therapy for malignant melanoma, small cell bronchogenic carcinoma (SCBC) or ovarian cancer. Among the patients with SCBC and melanoma, high correlations were observed between LASA scores for general well-being, mood and appetite. There was a significant relationship between performance status and LASA scores for general well-being, pain and appetite. Among patients with ovarian cancer, there was a significant association between performance status and LASA scores for general well-being, breathlessness and physical activity. Objective response category was related to change in LASA scores for pain. Changes in LASA scores during treatment reflected increased morbidity during radiotherapy in patients also receiving chemotherapy for SCBC. The LASA technique provides a convenient method for the assessment of quality of life in patients receiving cancer therapy, and potentially allows comparison of patient perception of treatment-related morbidities.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1983

On the receiving end--patient perception of the side-effects of cancer chemotherapy.

We conducted a survey to identify and rank side-effects perceived by 99 patients receiving cancer chemotherapy. Non-physical side-effects constituted 54% of the 15 most severe symptoms, and included the thought of coming for treatment, the length of time taken by treatment and having to have a needle. Major physical side-effects were vomiting, nausea and hair loss. Differences in ranking of severity of side-effects were evident when patient groups were divided by sex, age, marital status and domestic situation, as well as by diagnosis, treatment and response. Evaluation of patient perception of the severity of side-effects is an aid to striking the cost benefit balance when deciding whether to use cancer chemotherapy.

Adolescent↗
PubMed1983

Lorazepam as an adjunct to antiemetic therapy with haloperidol in patients receiving cytotoxic chemotherapy.

Twenty-seven consecutive patients were treated with 3 mg oral lorazepam and 2.5 mg intravenous haloperidol in an effort to improve patient tolerance of cytotoxic chemotherapy and decrease nausea and vomiting. Antiemetic efficacy and side-effects were assessed using a patient questionnaire. Vomiting either did not occur, or was considered to be of only moderate intensity in 22 patients (81%) and usually ceased within 24 hours of commencing chemotherapy. Similarly, nausea was either absent or of only moderate severity, lasting less than 48 hours in the majority of patients. Eight of 11 patients who had received similar previous cytotoxic treatment with antiemetic agents but not lorazepam considered that lorazepam and haloperidol had considerably improved their tolerance of chemotherapy. The side-effects of haloperidol and lorazepam were mild and well tolerated.

Anti-Anxiety Agents↗
PubMed1982

Single-agent versus combination antiemetic treatments in patients receiving cytotoxic chemotherapy.

We report the results of two clinical trials in which patients receiving either doxorubicin (Adriamycin)/cyclophosphamide or cis-platinum cytotoxic chemotherapy were assigned at random either a single or a combination antiemetic treatment. The aim of each trial was to assess whether combination antiemetic therapy would result in improved efficacy. Sixty patients commencing doxorubicin/cyclophosphamide therapy were divided in two random groups to receive either haloperidol or haloperidol plus amitriptyline, and 80 patients commencing cis-platinum therapy were divided at random to receive either metoclopramide or metoclopramide plus promethazine. No statistically significant differences were apparent between single and combination antiemetic regimens in either of the two treatment groups. Antiemetic agents were generally well-tolerated, but minor side effects were common. The failure of our combination antiemetic regimens to intensify the proven antiemetic efficacy of single agents emphasises the need for re-evaluation of currently used antiemetic agents and their dosage schedules.

Amitriptyline↗
PubMed1981

Information flow in the conduct of multicentred collaborative controlled clinical trials of cancer therapy.

Prospective randomized controlled clinical trials are a powerful tool for unbiased comparative evaluation of alternative treatment policies. Such trials must include relatively large numbers of patients, usually beyond the resources of any one clinical centre. Collaboration between centres is usually necessary and inevitably causes problems of communication at all stages of trial design and execution. Trial design demands agreement on the prior data base, and the writing of a trial protocol. The protocol must include precise depiction of trial objectives, eligibility criteria, randomization procedures, treatment policies, the end points by which effectiveness will be measured, and the records to be kept. It will also contain sections describing the scientific background and rationale of the trial, and statistical and ethical considerations. Once the trial is in progress, information must flow from the participating clinical institutions to a coordinating data centre; this will usually require the use of specially designed data collection forms. Most trials will require separate forms for initial registration, pre-therapy baseline information, sequential evaluation (flow sheet), and summaries when the patient reaches defined end-points. Additional forms may document specific treatment details, evaluation by a reviewer, and patient self-assessment scores or autopsy details. Attention to these aspects of study design will avoid later problems of misinterpretation, and will facilitate accurate and timely acquisition of data. Information flow from the coordinating centre to trial participants is also important, in order to maintain interest and patient accrual.

Australia↗
PubMed1981

Propranolol in schizophrenia. I. Comparison of propranolol, chlorpromazine and placebo.

Fifty-three hospitalized chronic schizophrenic patients were treated with either propranolol, chlorpromazine or placebo in a double-blind randomized trials for up to three months. Propranolol in a usual dose of 640 mg/day, produced marked cardiovascular effects but no improvement in schizophrenic symptomatology relative to placebo. The effects of chlorpromazine were small and inconsistent.

Blood Pressure↗