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Biomedical subjects

M R Cooper

Publications and source records attributed to M R Cooper.

At least 91 records · Page 5Linked to original sources
PubMed1991

The role of chemotherapy for node-negative breast cancer.

Approximately 25% of women with early stage breast cancer and negative axillary nodes will eventually die of metastatic disease. Some studies have shown a recurrence rate of 40% or more at 10 years in this relatively good prognostic group. The incidence of breast cancer continues to increase approximately 1% per year with a great increase in the frequency of early stage disease (particularly in situ carcinoma). The increased use of mammography and physical examination with appropriate follow-up will increase the frequency of diagnosis of node-negative patients compared with those with more advanced stages. Women with positive axillary nodes who are premenopausal benefit from adjuvant chemotherapy, whereas those who are postmenopausal have shown a clear reduction in mortality when treated with tamoxifen. It is even more reasonable to speculate that women with node-negative disease could have an even greater benefit from adjuvant therapy because they have a lower tumor burden at the time of diagnosis. Compared with earlier clinical adjuvant trials, more recent studies (1981-89) have shown a disease-free survival advantage for node-negative breast cancer patients treated with adjuvant chemotherapy. Hopefully, the differences noticed in disease-free survival will show a similar survival advantage with further observations. The results of these clinical trials suggest that adjuvant chemotherapy may be of benefit to patients with node-negative disease but do not support the contention that all node-negative patients with breast cancer should receive adjuvant chemotherapy. Some prognostic subgroups (tumor size greater than 2 cm) have shown an overall 10-year survival rate of 92% for women who have not received adjuvant therapy. The benefits versus toxicities of adjuvant therapy should be carefully evaluated before the initiation of adjuvant therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

A randomized trial of chemotherapy (L-PAM vs CMF) and irradiation for node positive breast cancer. Eleven year follow-up of a Piedmont Oncology Association trial.

158 evaluable patients with stage II, lymph node positive, carcinoma of the breast were randomized to adjuvant therapy with either melphalan (L-PAM) or cyclophosphamide, methotrexate, and fluorouracil (CMF) after mastectomy. In addition, patients were randomized to be treated with or without post-operative irradiation therapy (RT) in addition to their chemotherapy. At a median follow-up time of 11 years, there is no difference in time to relapse (P = 0.69) or survival (P = 0.55) among the four treatment groups. Multivariate analysis including treatment arm, age, race, tumor size, histologic type, performance status, time to onset of treatment, menopausal status, and number of positive nodes, revealed that only the number of positive nodes (less than 4 vs greater than or equal to 4) was related to disease-free and overall survival. Ten year relapse-free survival for patients with less than 4 positive nodes compared to those with greater than or equal to 4 positive nodes was 63% versus 30%, and overall survival 63% versus 41%, respectively. Patients who received post-operative radiation therapy had significantly less local recurrence than those treated with chemotherapy alone (P = 0.03) but without improvement in relapse-free or overall survival. In this trial, post-operative radiation therapy when added to chemotherapy decreased the risk of local recurrence without adverse effects on survival. Treatment outcome was not influenced by chemotherapy regimen, but differences may have been obscured by the small sample size.

Adult↗
PubMed1991

Effect of suramin on human prostate cancer cells in vitro.

Suramin, a polyanionic compound with known antiparasitic activity, has been shown to be adrenocorticolytic in primates and to have clinical efficacy in the treatment of patients with metastatic prostate cancer refractory to conventional hormonal manipulation. To better characterize the activity of suramin on prostate cancer biology, we studied the effect of the drug on plasma adrenal androgens of patients and on the human prostate adenocarcinoma cell lines PC-3, DU 145 and LNCaP-FGC. Five cancer patients treated with suramin had an approximate 40% decline in circulating androstenedione, dehydroepiandrosterone and dehydroepiandrosterone sulfate levels. The drug inhibited the colony formation in two of the three cell lines at concentrations clinically achievable in humans without excessive drug-related toxicity. The presence of suramin 300 micrograms./ml. partially inhibited the growth stimulatory effect of testosterone and basic fibroblast growth factor, but not that of epidermal growth factor. The cellular concentration of suramin following exposure to a single dose increases linearly over time in each of the cell lines with LNCaP-FGC accumulating the highest levels of the drug; cellular levels of suramin, not androgen or growth factor sensitivity, correlated with the sensitivity to the drug. The concentrations of prostatic acid phosphatase and prostatic specific antigen released by LNCaP-FGC cells in cell culture medium declined in the presence of increasing levels of suramin in a manner which exceeded the decrease in cell number. We conclude that suramin, aside from decreasing circulating androgens through its adrenocorticolytic effect, is also capable exerting a direct inhibitory effect on cell proliferation of prostate cancer cells, and interfere at a cellular level with the growth stimulatory effects of exogenous testosterone and basic fibroblast growth factor.

Adenocarcinoma↗
PubMed1991

Mood and clinical status in patients with multiple myeloma.

Two hundred ninety patients with a recent diagnosis of multiple myeloma were studied psychologically at the time of initial treatment. Physician- and patient-completed psychosocial scales were correlated with physical variables used to measure tumor load and physical status. A logistic regression model was used to analyze objective response to treatment. Indirect measures of response to treatment were obtained, and factors influencing survival duration were studied using a Cox regression model. If physical variables were controlled, there were no significant correlations between psychologic scores on entry and response to treatment or survival duration. Thus, the notion that mood influences disease outcome once the disease process has begun in patients with multiple myeloma is not supported by this data set.

Adult↗
PubMed1991

A review of the clinical studies of alpha-interferon in the management of multiple myeloma.

The treatment of multiple myeloma is multidisciplinary and requires attention not only to the primary disease itself but to its secondary manifestations. Melphalan remains the single most effective oral chemotherapeutic drug used to treat multiple myeloma. A major problem with the oral administration of the drug is its variable bioavailability. The presence of an L-phenylalanine moiety in the structure of melphalan makes it likely that gastrointestinal absorption occurs through the normal amino acid transport mechanisms and that the presence of food influences the drug's uptake. Another factor that complicates the bioavailability of this agent is the fact that melphalan undergoes spontaneous hydrolysis at physiologic pH. One of the controversies in myeloma therapy is the continuing debate over the possible superiority of complex, multiagent chemotherapy regimens compared with single melphalan and prednisone or cyclophosphamide and prednisone. It does appear that response frequencies are considerably greater with combination chemotherapy than with standard oral melphalan and prednisone treatment. It is probable that both approaches--single-agent chemotherapy with melphalan and prednisone versus combination chemotherapy--can play a role in remission induction therapy. It may be appropriate to treat the patient with a low tumor burden with melphalan and prednisone and treat more aggressive myeloma patients with triple alkylator therapy or other combinations of chemotherapy agents. The most promising activity of interferon alfa-2b (rIFN alpha 2b) in induction of myeloma remission appears to occur when rIFN alpha 2b is combined with multiple alkylating agents. Analysis of clinical trials suggests that sequential use of rIFN alpha 2b with cytotoxic therapy may be more active than when IFN alpha 2b is given concomitantly with cytotoxic therapy. It may be most plausible to use rIFN alpha 2b in maintenance of remission of myeloma. In the laboratory, interferons have the capacity to modulate oncogene expression and to decrease both in vitro colony formation and the labeling index of myeloma cells. Further, it has been shown that interferon can reduce the capacity for self-renewal in myeloma-forming cells. The following concepts will be discussed: 1. There is promising evidence that rIFN alpha 2b may improve the frequency and quality of remission in multiple myeloma when administered in an alternating schedule. There is some evidence that rIFN alpha 2b, when combined with cytotoxic therapy and given concomitantly, may be less active.(ABSTRACT TRUNCATED AT 400 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Use of suramin in treatment of prostatic carcinoma refractory to conventional hormonal manipulation.

Suramin and related compounds, in view of their growth factor and enzyme binding properties, represent in many respects a novel approach to the treatment of cancer. Although in this preliminary analysis of suramin use in the treatment of metastatic prostate cancer, the objective response rate does not appear impressive, much work still needs to be done to optimize suramin's administration to patients and to elucidate its various postulated mechanisms of action. The development of related compounds with more specific enzyme and growth factor antagonist properties is under way.

Adrenal Cortex↗
PubMed1990

The use of flow cytometry for the prognosis of stage II adjuvant treated breast cancer patients.

Characterization of breast cancer cells by histology, flow cytometry, and steroid receptors was performed on 197 Stage II breast node positive cancer patients given adjuvant chemotherapy, plus tamoxifen for patients with positive hormone receptors. Histologic and steroid receptor assays were performed using standard techniques; flow cytometric analysis was performed from paraffin-embedded blocks obtained from the primary tumor. Quality control studies on reproducibility, tissue heterogeneity, and analysis procedures have been included. Of the 197 patients studied, aneuploidy was found in 102 (52%); the median %S value was 8% with a range of 0.4% to 38%. Our results demonstrated that number of positive nodes, receptor status, and grade were of prognostic value. Cell cycle kinetic data were not of independent prognostic value in this series. However, ploidy could differentiate in prognosis in the receptor-negative subgroup. Patients with receptor-negative tumors had a significantly better overall survival if the tumor was diploid in nature. Cell kinetics was not significantly prognostic for either receptor subgroup, although patients with higher %S tended to have better relapse-free and overall survival. This is in disagreement with other studies and may demonstrate that treatment has confounded our results and diminished the ability of flow cytometry data to help predict outcome.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Phase II study of MOPLACE chemotherapy for patients with previously treated Hodgkin's disease: a CALGB study.

To further evaluate possible non-cross-resistant regimens in Hodgkin's disease, a phase II trial utilizing antimetabolites and etoposide was initiated by the Cancer and Leukemia Group B (CALGB). Etoposide was included because of its known efficacy in relapsed Hodgkin's disease and to evaluate for synergy with an alkylating agent and vincristine. Cytosine arabinoside and methotrexate were included to evaluate their effectiveness in rapidly growing resistant disease. Forty-two patients with previously treated Hodgkin's disease were entered, of which 37 are evaluable for response and toxicity. All patients had at least 2 prior regimens of chemotherapy and 59% had additional radiation therapy. Complete and partial response was observed in 61%; there were 32% complete responders. Duration of complete response was a median of 8 months (range 2-28+ months). Duration of partial response was 7 months (range 1-17 months). Three patients remain in complete remission at 19, 19, and 28 months. Major toxicity was hematologic with severe or life-threatening toxicity in 54%. There was one patient with a fatal infection. Non-hematologic toxicity, save for nausea and vomiting, was mild and uncommon. There were two fatal and one severe pulmonary toxicities reported in patients who had previous exposure to bleomycin and mediastinal radiation. Three had interstitial pneumonitis and one pulmonary emboli. The interstitial pneumonitis was thought to be drug related. Survival of the entire group is estimated at 61% at 12 months. We conclude that MOPLACE is an effective regimen with an appreciable complete response rate in this heavily pretreated group of patients. Hematologic and pulmonary toxicities are severe and may necessitate dose modifications. The use of etoposide containing combinations requires further study as primary therapy in untreated patients.

Adolescent↗
PubMed1990

A phase II trial of PEG-L-asparaginase in the treatment of non-Hodgkins lymphoma.

A polyethylene glycol conjugate of L-asparaginase (PEGLA) was administered to 21 patients with refractory non-Hodgkin's lymphoma. The dose given was 2,000 mu/m2 intramuscularly every 2 weeks. Eligibility required at least one prior trial of chemotherapy and ambulatory performance status. At entry, all patients had measurable lesions and documented disease progression. The median age of the patients was 61 years; 18 (86%) were ambulatory with minimal symptoms, 12 patients (57%) had 3 or more prior regimens, and 13 (62%) had stage IV disease. Histologic subtype was low grade in 11 patients (52%), intermediate in 7 (33%), high grade in 2 (10%) and unclassifiable in one (5%). There were two partial responses (11%) noted (95% confidence interval of response of 1-30%). Eleven patients (52%) were removed from study due to disease progression. Nine patients (43%), required removal for toxicity (7 for protracted nausea and vomiting and 2 for confusion). One patient died of sepsis while on study but this was not considered drug related. Almost one third of patients complained of fatigue or loss of appetite. Nausea and vomiting occurred in approximately half the patients and was moderate to severe in 9. Diarrhea and abdominal pain were also noted in one-third of those treated. Changes in the partial thromboplastin time and fibrinogen were noted in most patients but resulted in no bleeding complications. In this trial, PEGLA displayed modest activity in a heterogenous group of patients with progressive non-Hodgkin's lymphoma.

Adult↗
PubMed1990

Carboplatin in malignant mesothelioma: a phase II study of the Cancer and Leukemia Group B.

Carboplatin (400 mg/m2) was given at 28-day intervals to 41 patients with malignant mesothelioma. In all, 40 patients were eligible and evaluable for response. Partial responses were seen in 2 cases (5%); regression of evaluable disease, in 1 patient (2%); and stable disease, in 19 subjects (48%). A median of two doses of carboplatin per patient resulted in mild toxicity. Leukopenia (less than or equal to 2,000 cells/microliters) and thrombocytopenia (less than 100,000 cells/microliters) were seen in only 6% and 20% of the patients, respectively. Median survival from study entry was estimated at 7.1 months, with a 1-year survival of 25% +/- 7%. Carboplatin given at a dose of 400 mg/m2 at 28-day intervals shows minor activity against malignant mesothelioma.

Adult↗
PubMed1990

Evaluation of an oncology curriculum.

This report describes and presents an evaluation of the undergraduate component of the Cancer Education Program at The Bowman Gray School of Medicine. New learning objectives on cancer were introduced into the second and third year of the Medical School curriculum. A twenty-five question multiple choice examination measured the accomplishment of the new objectives. Students in the class of 1985, who did not receive instruction on the new objectives as part of their formal medical education, served as a control. Students in the classes of 1986 and 1987, who respectively received partial and full exposure to the new objectives, served as experimental groups. Despite limitations in the evaluation procedure, data obtained from the study suggested the possibility of a small but meaningful increase in overall knowledge and specific gains in both students' knowledge and their perceptions of being better prepared to deal with psychosocial aspects of cancer.

Curriculum↗
PubMed1990

High- versus standard-dose megestrol acetate in women with advanced breast cancer: a phase III trial of the Piedmont Oncology Association.

One hundred seventy-two patients with advanced breast cancer were randomized to receive oral standard-dose megestrol acetate (MA), 160 mg/d or high-dose MA, 800 mg/d. All but two patients had one prior trial of tamoxifen therapy for either metastatic disease (74%) or as adjuvant treatment (26%). Pretreatment characteristics were similar for both arms. High-dose MA resulted in a superior complete plus partial response rate (27% v 10%, P = .005), time to treatment failure (median, 8.0 v 3.2 months, P = .019), and survival (median, 22.4 v 16.5 months, P = .04) when compared with standard-dose therapy. These differences remained significant after adjustment for other covariates. Thirty-four patients were given high-dose MA after failure of standard-dose MA treatment, and none responded. Weight gain was the most distressing side effect, with 13% of standard-dose and 43% of high-dose patients gaining more than 20 lbs. Four major cardiovascular events occurred in patients receiving high-dose treatment and one in patients given standard doses. Other toxicity was modest. High-dose MA may represent a significant improvement in secondary endocrine therapy for advanced breast cancer patients refractory to initial endocrine treatment, but its use on a regular basis should be reserved until these results are confirmed by other clinical trials.

Adult↗
PubMed1990

Quality of life assessment of Hodgkin's disease survivors: a model for cooperative clinical trials.

With the growing number of patients surviving cancer, there has been an increasing concern with their long-term adaptation. Given the large number of Hodgkin's disease survivors, it was possible to conduct a study of their psychosocial adaptation. Two hundred seventy-three survivors of advanced Hodgkin's disease were interviewed over the telephone concerning the impact of cancer upon their lives, in terms of their psychological, social, and sexual functioning. The level of psychological distress was elevated by one standard deviation above normal on the Brief Symptom Inventory (BSI), for both men and women. Survivors in greater distress reported more problems in other areas of functioning, including sexual, social, vocational, and persistent conditioned nausea.

Adaptation, Psychological↗
PubMed1989

Efficacy of adjuvant chemotherapy in high-risk node-negative breast cancer. An intergroup study.

We randomly assigned 536 women who had undergone either a modified radical mastectomy or a total mastectomy with low axillary-node dissection for potentially curable breast carcinoma to receive adjuvant chemotherapy or no-treatment observation. The patients were considered at high risk for recurrence because they had either an estrogen-receptor-negative tumor of any size or an estrogen-receptor-positive tumor at least 3 cm in diameter with no histopathological evidence of axillary-node involvement. The chemotherapy consisted of six four-week cycles of cyclophosphamide (100 mg per square meter of body-surface area orally on days 1 through 14), methotrexate (40 mg per square meter intravenously on days 1 and 8), fluorouracil (600 mg per square meter intravenously on days 1 and 8), and prednisone (40 mg per square meter orally on days 1 through 14). Treatments were balanced with respect to patients' characteristics. The analysis included 406 eligible patients who were entered in the study before October 1, 1987. The overall disease-free survival among patients treated with the four-drug regimen was 84 percent, as compared with 69 percent for the control group, at a median follow-up of three years (P = 0.0001). A treatment benefit was also observed in premenopausal and postmenopausal patients as well as in patients with estrogen-receptor-positive or with estrogen-receptor-negative tumors. Severe or life-threatening hematologic toxicity was encountered in 33 percent of the treated patients, with one death. Our results indicate that adjuvant chemotherapy with six cycles of cyclophosphamide, methotrexate, fluorouracil, and prednisone is effective in improving three-year disease-free survival among high-risk patients with axillary-node-negative, operable breast cancer. An analysis of the effect of treatment on survival awaits a longer follow-up.

Adult↗
PubMed1989

Chemoinfusion of the hepatic artery for metastases to the liver.

During a five year period, 69 patients were treated for carcinoma of the liver (seven primary tumors and 62 metastatic tumors) with 5-fluorodeoxyuridine (5-FUDR) administered through a hepatic artery (n = 62) or portal vein (n = 3) implantable infusion pump. Ten patients proved to have previously unsuspected extrahepatic nodal metastases at laparotomy for pump insertion. 5-FUDR was given in 14 day cycles for three months. At the end of that period and at three month intervals thereafter (mean follow-up time of 18 months, a range of one to 60 months), patients were evaluated with roentgenograms of the chest, liver function tests, carcinoembryonic antigen levels, radionuclide scans and computed tomography. Thirty-five patients had a partial response, nine had stabilization of the disease and 25 had progression of the disease (five during therapy, who were given mitomycin C). Median regression was 6.8 months (a range of three to 18 months). Six of the 35 partial responders, three of the nine patients with stabilization and ten of the 25 patients with progression had extrahepatic visceral disease. Survival time averaged 18.4 months (a range of five to 60 months) for the partial responders, 12.6 months (a range of two to 40 months) for patients with stabilization and seven months (a range of one to 17 months) for those with progression of the disease.

Adult↗