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Biomedical subjects

R Stuart-Harris

Publications and source records attributed to R Stuart-Harris.

47 records · Page 3Linked to original sources
PubMed1985

Endocrine effects of low dose aminoglutethimide as an aromatase inhibitor in the treatment of breast cancer.

The endocrine effects of low dose (62.5 mg, twice a day) aminoglutethimide (AG), without hydrocortisone (HC), escalating at monthly intervals to a conventional dose of AG (500 mg twice a day) combined with HC, were studied in 33 postmenopausal breast cancer patients. Pretreatment serum concentrations of oestrone (E1) and oestradiol (E2) were significantly suppressed by 62.5 mg of AG twice a day. Although further suppression of E1 appeared to occur with 125 mg of AG twice a day, this was not statistically significant. For E1 and E2, higher doses of AG or combined AG and HC failed to cause further significant suppression compared with that obtained at 125 mg of AG twice a day. Significant rises in serum androstenedione were found with all doses of AG alone, although pretreatment concentrations of androstenedione were not significantly altered by combined AG and HC treatment. Mean pretreatment concentrations of dehydroepiandrosterone sulphate (DHA-S) were significantly suppressed by 62.5 mg of AG twice a day and further marked suppression occurred on combined AG and HC therapy. Serum cortisol, aldosterone and plasma ACTH concentrations showed no significant alterations throughout treatment. Aminoglutethimide is as effective at 125 mg twice a day without HC in its suppression of oestrogen levels as at 500 mg twice a day with HC, and its use in this form warrants clinical evaluation.

Adrenocorticotropic Hormone↗
PubMed1985

Cisplatin, vinblastine, and bleomycin in inoperable non-small cell lung cancer.

Forty two patients with inoperable non-small cell lung cancer were entered into a phase II study of the combination chemotherapy regimen PVB (cisplatin 60 mg/m2 by intravenous infusion over two hours on day 1, vinblastine 4 mg/m2 by intravenous bolus on days 1 and 2, and bleomycin 15 mg intramuscularly on days 1, 8, and 15), repeated at three weekly intervals. Twelve of 40 evaluable patients (30%) achieved partial responses; there were no complete responses. The median duration of response was 16 weeks (range greater than 8-73 weeks). The median survival of responding patients calculated from entry to the study until death (40 weeks) was superior to that of patients failing to respond (15 weeks). Treatment was accompanied by signs of moderate toxicity, particularly myelosuppression, nausea and vomiting, alopecia, and neuropathy. One patient died from a neutropenic infection. PVB is a moderately toxic regimen for non-small cell lung cancer and appears similar in efficacy and toxicity to high dose cisplatin and vindesine.

Adenocarcinoma↗
PubMed1984

Low-dose aminoglutethimide in treatment of advanced breast cancer.

The clinical and endocrine effects of low-dose aminoglutethimide without hydrocortisone in patients with advanced breast cancer were investigated. In a dose escalation study low-dose aminoglutethimide alone (62.5-125 mg twice daily) was as effective as conventional doses with hydrocortisone in lowering serum oestrone and oestradiol concentrations but caused minimum adrenal inhibition, as assessed by serum dehydroepiandrosterone sulphate. 11 of 57 (19%) evaluable patients had tumour regression by objective criteria on this treatment, but the frequency of side-effects was similar to that with conventional doses. Low-dose aminoglutethimide is active in the treatment of breast cancer. It appears to work by inhibition of the aromatase enzyme system in peripheral tissues rather than adrenal suppression.

Adrenal Glands↗
PubMed1983

Mitoxantrone (Novantrone) as single agent and in combination chemotherapy in the treatment of advanced breast cancer.

Nineteen out of 62 evaluable patients with advanced breast cancer achieved an objective tumour response to mitoxantrone (31%) given in a dose of 12-14 mg/m2 by i.v. infusion repeated at 3-weekly intervals. The response rate in patients who had received no prior chemotherapy for advanced disease was 35%, compared with 22% in previously treated patients. Median duration of response was 10 months. Responses were seen in three out of nine patients who failed to respond to adriamycin. Neutropenia was dose limiting and eight out of 65 patients evaluable for toxicity had a neutropenic infection. Two patients developed readily reversible cardiac failure and two more developed physiological features of cardiac impairment, all after prolonged treatment. Other toxicities were mild and the drug was well tolerated; severe alopecia occurred in only one patient. Nine patients treated with a combination of mitoxantrone, vincristine and methotrexate all developed leukopenia with a mean white blood count of 1400/mm2 (range 200-2400) although no episodes of neutropenic infection were seen and the combination was otherwise well tolerated. Mitoxantrone is an active, well tolerated drug in the treatment of advanced breast cancer and merits further evaluation.

Adult↗
PubMed1983

Chlorpromazine, placebo and droperidol in the treatment of nausea and vomiting associated with cisplatin therapy.

The use of cisplatin may be associated with severe nausea and vomiting. Two separate, randomized, double-blind trials, comparing the anti-emetic effect of chlorpromazine with placebo and chlorpromazine with droperidol, were conducted in patients receiving cisplatin for ovarian cancer. Chlorpromazine was statistically superior to placebo in the control of nausea and vomiting in those patients treated with chlorpromazine had significantly less nausea than with droperidol, but there were no other significant differences between chlorpromazine and droperidol. Toxicities of chlorpromazine and droperidol were similar. Chlorpromazine shows useful activity against cisplatin nausea and vomiting.

Chlorpromazine↗
PubMed1982

Biliary elimination of cyclophosphamide in man.

A 72-year-old male with a lymphoma and obstructive jaundice received 900 mg cyclophosphamide IV as a part of a chemotherapeutic regimen whilst external biliary drainage was in progress. Plasma, urinary, and biliary pharmacokinetics of cyclophosphamide and nitrobenzylpyridine (NBP)-alkylating metabolites were studied. In 32 h 891 ml bile was collected, and this contained unchanged cyclophosphamide and NBP-alkylating material. Despite fluctuations in biliary flow, estimates of the half-life of cyclophosphamide from plasma, urine, and bile were similar. Good correlation existed between plasma and biliary cyclophosphamide concentrations after the initial plasma had been completed. The ratio of bile to plasma concentrations was 0.7 and showed no time dependence, as evidenced by a lack of hysteresis in the correlation curve. Of the administered dose, 3.5% was excreted as unchanged cyclophosphamide in the bile over 32 h. NBP-alkylating activity was found in bile up to 25 h but not after this time, despite the presence of unchanged cyclophosphamide in plasma. NBP-alkylating material was not found in the bile when it could not be detected in plasma, and vice versa.

Aged↗
PubMed1982

Chemotherapy of endodermal sinus tumour (yolk sac tumour) of the ovary: preliminary communication.

Eight patients presenting with endodermal sinus tumour of the ovary have been treated with combination chemotherapy using cisplatin, bleomycin and vinblastine (PVB). Complete remission occurred in 7 out of 8 cases, all of whom are alive and well 3 to 33 months later. These preliminary results are compared with our own past experience and recent reports in the literature. It is concluded that the PVB regimen is probably as effective in female germ cell tumours as it is in testicular teratoma.

Adolescent↗