Search PubMed⌕ Search

Biomedical subjects

M A Richards

Publications and source records attributed to M A Richards.

At least 19 recordsLinked to original sources
PubMed1992

Measuring coping in breast cancer.

The emotional distress associated with breast cancer varies between individual women. These variations may be accounted for by differences in cognitive and behavioural coping responses to diagnosis. This study has attempted to develop a reliable, situation-specific approach to the measurement of coping responses in women with breast cancer. It has adapted a general coping questionnaire and modified an interview-based schedule for coping with cancer. The strengths and weaknesses of the interview and self-report methods of assessment are highlighted. Consistent results from these complementary approaches have been obtained. Both indicate the extensive use of cognitive avoidance and positive reappraisal. It has been shown that the majority of patients use a wide repertoire of coping responses which challenges the notion of mutually exclusive coping styles. These measures may be employed to examine the relationship between women's thoughts and behaviours in response to the diagnosis and treatment of breast cancer and subsequent psychological outcome.

Adaptation, Psychological↗
PubMed1992

Doxorubicin in advanced breast cancer: influence of schedule on response, survival and quality of life.

The influence of scheduling of doxorubicin on response, survival and quality of life was assessed in a randomised trial in patients with advanced breast cancer, none of whom had previously received cytotoxic chemotherapy for advanced disease. 28 patients received 75 mg/m2 doxorubicin every 3 weeks for four courses (arm 1) and 31 patients received 25 mg/m2 weekly for 12 courses (arm 2). Response rates and median time to progression were similar in the two arms and median survival was 8 months in both arms. However, amongst patients receiving treatment every 3 weeks, psychological distress measured using the Rotterdam symptom checklist fell significantly over the course; no such change was observed in those treated weekly. Physical symptoms related to cancer improved during treatment similarly for both groups.

Adult↗
PubMed1992

DNA flow cytometry and response to preoperative chemotherapy for primary breast cancer.

Between October 1988 and June 1990, 22 patients with locally advanced, inoperable breast cancer entered a pilot study of four cycles of anthracycline based cytotoxic chemotherapy followed by surgery and tamoxifen. Fine needle aspirate samples of tumour were obtained for DNA flow cytometry before treatment and during the first cycle of chemotherapy. 21 patients are eligible for assessment of response and toxicity. Chemotherapy was well tolerated with greater than WHO grade 2 vomiting or stomatitis in 4 patients. Granulocytopenia less than 10(9)/l was noted in 16/21 patients but there were no episodes of neutropenic sepsis. There were 7 complete responses (CR) and 11 partial responses (PR), giving an overall response rate to chemotherapy (CR+PR) of 18/21 (86%). Responses were observed more commonly in patients who had aneuploid tumours (P = 0.06) and in patients whose tumours had a high S-phase fraction (P = 0.1). Tumours which responded to chemotherapy (CR or PR) had a significantly higher median SPF compared with tumours which did not regress (P less than 0.05). There was no consistent pattern of change in SPF values during the first cycle of chemotherapy, either for patients who responded to treatment or for those whose tumours did not regress. This combination therapy is well tolerated with a high response rate. The results of this pilot study support the recent suggestion that tumours with rapidly proliferating, aneuploid populations of cells exhibit the best short-term response to chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Clinical pharmacokinetics of epirubicin: the importance of liver biochemistry tests.

The influence of liver biochemistry tests on epirubicin pharmacokinetics has been investigated in 52 women with advanced breast cancer, 27 of whom had radiologically proven liver metastases. Patients received epirubicin 12.5-120 mg m-2 given as an i.v. bolus. Epirubicin levels were measured by HPLC following the first cycle of treatment. Epirubicin elimination, expressed as clearance (dose/AUC), in the 22 patients with normal AST and bilirubin was compared with that of 30 patients with a raised AST +/- raised bilirubin. Epirubicin clearance was significantly reduced in the patients with a raised AST, whether their serum bilirubin was normal (22 patients) or elevated (eight patients). In the 30 patients with a raised AST +/- raised bilirubin, epirubicin clearance correlated strongly with the level of AST (r = -0.72) but not with serum bilirubin, alkaline phosphatase, albumin or creatinine. Using a multiple regression analysis, AST was the only one of these biochemical variables predictive of epirubicin clearance (r2 = 0.47, P = 0.0006). We conclude that a raised serum AST is a more sensitive and reliable measure of abnormal epirubicin pharmacokinetics than increased bilirubin. These findings have implications for anthracycline treatment in patients with abnormal liver biochemistry.

Adult↗
PubMed1992

Combination chemotherapy versus melphalan and prednisolone in the treatment of multiple myeloma: an overview of published trials.

PURPOSE: A meta-analysis was performed to compare survival after treatment with melphalan and prednisolone (M + P) with that after combination chemotherapy (CCT) in patients with multiple myeloma. METHODS: Meta-analysis was performed on 18 published trials comprising 3,814 patients comparing M + P with CCT. Two-year survival percentages with observed and expected deaths at 2 years were calculated for each trial, and the overview methodology was applied to these figures. RESULTS: Overall results from the 18 trials suggest that there is no difference in efficacy between the two treatments. This finding, however, masks a highly significant correlation between 2-year survival rates for M + P-treated patients in individual studies and the difference between the M + P and CCT 2-year survival rates for that study (r = .69; P = .0008). In separate overviews, those studies with a high M + P 2-year survival rate showed a survival difference in favor of M + P (P = .02), whereas those with a low rate suggested a difference in favor of CCT (P V .07). Comparison of the 2-year survival rates in the M + P treatment arms of each of the studies with available data showed an inverse correlation between survival and the proportion of patients with either poor performance status (P less than .001) or immunoglobulin A (IgA) M band (P = .02). CONCLUSIONS: These results imply that M + P is superior for patients with an intrinsically good prognosis and inferior for those patients with a poor prognosis. If reliable prognostic factors can be established for this disease, they could be used to select therapy for individual patients.

Actuarial Analysis↗
PubMed1992

Advanced breast cancer in Egyptian women: clinical features and response to endocrine therapy. The Anglo-Egyptian Health Agreement Collaborative Study.

Response to endocrine therapy and its relationship to the clinical features of the disease were studied in 84 Egyptian patients with inoperable, locally advanced or metastatic breast cancer. Twenty-four premenopausal patients were treated by oophorectomy with or without concurrent prednisolone. Only one of 20 evaluable patients achieved an objective response. Median time to progression for premenopausal patients was 3 months. Sixty postmenopausal patients received tamoxifen 10 mg twice daily either alone or with prednisolone. Fourteen of 57 (25%) evaluable patients achieved an objective response (four complete remission, 10 partial remission). Median duration of response was 13 months and median time to progression for all postmenopausal patients was 5 months (range 1-30 months). The outcome for postmenopausal patients was similar to that found in a parallel study at Guy's Hospital, London. The response rate for premenopausal Egyptian patients was, however, disappointing and lends support to the claim that breast cancer in Egyptian women is particularly aggressive.

Adult↗
PubMed1991

Timing of surgery during menstrual cycle and survival of premenopausal women with operable breast cancer.

Timing of operation in relation to menstrual phase might affect outlook in premenopausal women with operable breast cancer. We examined the records of 249 such women treated between 1975 and 1985, and compared overall and recurrence-free survival in those whose operation was 3-12 days after their last menstrual period (LMP) (group 1, n = 75) with those in whom it was 0-2 or 13-32 days after LMP (group 2, n = 174). Overall and recurrence-free survival were greatly reduced in group 1 women (p less than 0.001 for both). Actuarial survival at 10 years was 54% in group 1 versus 84% in group 2. This effect was independent of other factors, was of much the same importance as nodal status in multivariate analysis, was largely confined to histologically node-positive cases, seemed to be greater in women with small tumours (less than or equal to 2 cm), and was seen in patients with oestrogen-receptor positive and negative tumours. Thus phase of menstrual cycle at operation is of great importance for long-term outlook in premenopausal women with breast cancer.

Actuarial Analysis↗
PubMed1991

A mathematical model relating response durations to amount of subclinical resistant disease.

A mathematical model is presented which seeks to determine, from examination of the response durations of a group of patients with malignant disease, the mean and distribution of the resistant tumor volume. The mean tumor-doubling time and distribution of doubling times are also estimated. The model assumes that in a group of patients there is a log-normal distribution both of resistant disease and of tumor-doubling times and implies that the shapes of certain parts of an actuarial response-duration curve are related to these two factors. The model has been applied to data from two reported acute leukemia trials: (a) a recent acute myelogenous leukemia trial was examined. Close fits were obtained for both the first and second remission-duration curves. The model results suggested that patients with long first remissions had less resistant disease and had tumors with slower growth rates following second line treatment; (b) an historical study of maintenance therapy for acute lymphoblastic leukemia was used to estimate the mean cell-kill (approximately 10(4) cells) achieved with single agent, 6-mercaptopurine. Application of the model may have clinical relevance, for example, in identifying groups of patients likely to benefit from further intensification of treatment.

Humans↗
PubMed1991

Comparative pharmacokinetics of doxorubicin given by three different schedules with equal dose intensity in patients with breast cancer.

The pharmacokinetics of doxorubicin given according to three different schedules with a similar dose-time intensity have been studied and compared in 16 women with metastatic breast cancer. Six patients were treated with doxorubicin 75 mg/m2 by i.v. bolus repeated every 3 weeks; 5 patients received doxorubicin by 4-day continuous infusion every 3 weeks (4 at 75 mg/m2 and 1 at 60 mg/m2); 5 patients received 25 mg/m2 by i.v. bolus given weekly. Timed blood samples were collected and plasma levels of doxorubicin and its metabolite doxorubicinol were measured by high-performance liquid chromatography with fluorescence detection. Peak plasma concentrations were measured, and areas under the concentration-time curves calculated. Peak plasma levels of doxorubicin were significantly lower with the 4-day infusion than with either of the bolus injections. The 4-day infusion, however, gave significantly greater total exposure to doxorubicin and doxorubicinol, as indicated by area under the concentration-time curve, than weekly or 3-weekly bolus treatment. A single bolus injection of doxorubicin 25 mg/m2 yielded a total exposure to doxorubicin approximately half that achieved with a 75 mg/m2 bolus injection. Over a 3-week period, therefore, total exposure to doxorubicin would be greater with the weekly low-dose schedule than with the 3-weekly administration. We conclude that drug scheduling has significant effects on doxorubicin pharmacokinetics.

Breast Neoplasms↗
PubMed1991

High-dose epirubicin as primary chemotherapy in advanced breast carcinoma: a phase II study.

A total of 40 patients with metastatic breast cancer were treated with 120 mg/m2 i.v. epirubicin every 3 weeks for a maximum of 10 cycles. Nine achieved a complete response and 17 showed a partial response, for an objective response rate of 65% (95% confidence interval, 47%-83%); the median duration of response was 7 months (range, 1-15 months) and median survival amounted to 13 months (range, 2-20 months). Leucopenia (grade 2 or 3) was seen in 14 patients on day 21 of the cycle. A subset of nine patients underwent blood counts on day 10, when all had marked neutropenia (less than 1 x 10(9)/l). Other toxicity was frequent and included nausea/vomiting (80%), alopecia (95%) and stomatitis (35%). Five patients showed a significant fall in cardiac output, but this reverted to normal after treatment. Epirubicin should have a role in the development of high-dose regimens for the treatment of advanced breast cancer.

Adult↗