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Biomedical subjects

M R Cooper

Publications and source records attributed to M R Cooper.

At least 181 records · Page 10Linked to original sources
PubMed1981

Chemotherapy vs. chemoimmunotherapy with methanol extraction residue of Bacillus Calmette-Guerin (MER) in advanced breast cancer: a randomized trial by the Piedmont Oncology Association.

Effects of the addition of MER, a nonspecific, nonviable immunostimulant, to two combination chemotherapy programs were explored in patients with metastatic breast cancer. Patients were randomized to either CDVFP [cyclophosphamide (C), doxorubicin (D), vincristine (V), fluorouracil (F) and prednisone (P)] or CD alternating with methotrexate (M) and F (CD/MF). Each group was also randomized to receive MER, 0.4 mg S.C. every four weeks or no immunotherapy. The response rates were CDVFP 56%, CDVFP + MER 54%, CD/MF 43%, and CD/MF + MER 43%. No significant differences were noted in response rate. Median durations of response and survival were similar for each group: CDVFP 16.2 and 25.2 months, respectively; CDVFP + MER 14.0 and 23.3 months, CD/MF 12.1 and 26.1 months, and CD/MF + MER 15.5 and 25.6 months. Patients who achieved CR frequently had soft-tissue disease (7/17) and patients with disease in 1 or 2 metastatic sites had a significantly higher response rate than those in greater than or equal to 3 sites. MER did not enhance response rate, duration of response, or survival. Also MER did not diminish myelosuppression.

Antineoplastic Agents↗
PubMed1981

Cyclophosphamide versus cyclophosphamide, methotrexate, and 5-fluorouracil in advanced prostatic cancer: a randomized trial.

Thirty-two evaluable patients with metastatic carcinoma of the prostate were entered into a prospective randomized trial comparing cyclophosphamide (CYC) with a combination of cyclophosphamide, methotrexate, and fluorouracil (CMF). Progressive disease after endocrine manipulation was noted in 97% (31/32) of patients before entry. Stable disease (S) was observed in 9 of 17 patients treated with CYC. One partial response (PR) and seven stable responses occurred in the 15 CMF patients. Median duration of stable response was 4.5 months for CYC and 4.5 months on CMF. Median survival of patients with PR and S receiving CYC was 10.1 and for CMF 8.8 months. Patients with progressive disease survived a median 1.7 and 2.6 months with CYC and CMF, respectively. Toxicity was moderate, and no deaths were attributable to sepsis or bleeding. Almost all patients in this study had bone lesions as the dominant site of disease; this made objective assessment of response difficult. There was no significant improvement in response conferred by the combination regimen. Although patients with metastatic prostatic cancer may benefit from chemotherapy, impressive clinical responses are uncommon.

Aged↗
PubMed1981

A prospective study of histocompatible leukocyte and platelet transfusions during induction chemotherapy of adult acute nonlymphocytic leukemia.

A prospective clinical trial was conducted to test the effectiveness of granulocyte transfusions during induction chemotherapy of patients with adult acute non-lymphocyte leukemia. Thirty-eight patients who received prophylactic granulocyte transfusions from related donors when their phagocyte counts decreased to less than 1000 microliter were compared to twenty-five controls who did not have qualified donors from which to obtain granulocyte transfusions. The frequency of complete remissions (CR) (28/38 versus 7/25) was significantly greater for the granulocyte transfusion group than for controls. Patients older than 45 responded more often in the transfused group (P less than 0.025) when compared to the similar age group in controls. Both duration of complete remission and survival were greater in the granulocyte transfused group. However, these differences were not statistically significant. Survival for all responders (complete plus partial remission) was longer for the granulocyte transfusion group (P = 0.01). No significant difference in frequency or severity of either infection or hemorrhage was noted in the two groups. The advantage noted in this study largely occurred in patients older than 45 and this suggests that this age group is more likely to respond if they have histocompatible donors from which to obtain granulocyte and platelet transfusions. Immune mechanisms may be involved in the beneficial effects observed with HLA compatible granulocyte transfusions.

Adolescent↗
PubMed1981

Pharmacokinetics of vincristine sulfate in adult cancer patients.

Vincristine concentration in serum from 1 min to 72 hr was measured by radioimmunoassay in 14 patients with cancers following i.v. bolus injection of vincristine sulfate at 0.45 to 1.30 mg/sq m. The pharmacokinetic data were analyzed by a nonlinear least-square regression program NONLIN. A three-compartmental open model fitted the raw data better than a two-compartmental model. The mean half-lives of the triphasic decay curves alpha, beta, and gamma were 1.9, 19.2, and 1359 min (22.6 hr), respectively. The apparent volume of the central compartment and the volume of distribution at steady state (Vdss) per 1.73 sq m body surface area were 4.1 and 167.6 liters, respectively. The plasma clearance was 141.9 ml/min/1.73 sq m, and the area under the concentration X time curve from 0 to infinity (AUC0 infinity) for 2 mg vincristine was 21,689 nM.min. Linear regression analysis of the data gave evidence for increasing plasma clearance at higher doses of vincristine. In patients with higher platelet counts, lower AUC0 infinity values were obtained, suggesting a possible interaction of vincristine with blood platelets. Our results, a large Vdss, a long biological half-life, and a low rate-limiting rate constant from Compartment 3 to the central compartment (k31), indicate an avid tissue binding and a slow drug release from the body tissues which may account for drug-related neurotoxicity.

Adult↗
PubMed1980

A new effective four-drug combination of CCNU (1-[2-chloroethyl]-3-cyclohexyl-1-nitrosourea) (NSC-79038), vinblastine, prednisone, and procarbazine for the treatment of advanced Hodgkin's disease.

Five hundred and sixty-six patients with either Stage III or IV Hodgkin's disease were prospectively randomized to test whether CCNU and/or vinblastine are more effective than mechlorethamine and/or vincristine with procarbazine and prednisone. The combination of CCNU, vinblastine, procarbazine, and prednisone (CVPP) was shown to be a highly effective program with a complete response frequency of 69%. The use of CCNU as part of the induction program was also shown to be the most significant determinant of prolonged remissions (P = .025). Reduced vomiting and neurotoxicity, as well as the oral administration, were the chief advantages of the CVPP as compared with MOPP. These factors resulted in improved patient and physician compliance. The MVPP regimen was also shown to be a highly effective regimen with a complete response frequency of 73% in patients without prior exposure to chemotherapy. However, the induction regimens containing vinblastine were associated with a significantly higher frequency of fatal hematopoietic toxicities than the induction regimens containing vincristine (P = .05). This higher frequency was almost exclusively seen in the elderly or in patients previously treated with both chemotherapy and radiotherapy. At this time, the remission durations maintained by vinblastine with periodic reinforcement are longer when compared with vinblastine maintenance alone (P = .06), but there is no corresponding increase in survival.

Adult↗
PubMed1980

Proline isomerism in the protein folding of ribonuclease A.

The guanidinium chloride-unfolded state of ribonuclease A was found to be an equilibrium mixture of slow- and fast-refolding forms of the protein chain, as has been suggested. Both forms appear to have the same spectroscopic observables as judged by the relative changes in fluorescence emission and polarization. The equilibrium between them is thermally dependent, with deltaHapp equal to -1.4 kcal/mol. The activation energy Ea is equal to 18 kcal/mol. These findings are consistent with the proposal that cis-trans isomerism of peptide bonds that are NH2-terminal to proline residues is responsible for the slow phase of RNase A refolding. However, the actual dependence of the magnitude of the slow reaction on initial, prefolding temperature cannot be explained by a model in which the proline configurations of the fast refolding form must be identical to those of the native protein, as has been suggested. Instead, the data reveal that, although the native structure of RNase A contains two cis prolines, cis isomers need not be present in the fast-refolding form in order for folding to occur.

Calorimetry↗
PubMed1980

Advanced epidermoid lung cancer: prolonged survival after chemotherapy.

The charts and pathologic reports for 4 patients seen at our institution with advanced incurable epidermoid carcinoma of the lung, who had prolonged disease-free survival after chemotherapy, were reviewed. All patients had Stage III bronchogenic carcinoma. Our study indicates that patients with epidermoid carcinoma of the lung who achieve a complete response have a better survival than those patients who have a partial response or no response. All complete responses were achieved after two to three months of chemotherapy, and if a response is not seen by then a modification of the treatment program is recommended. We propose that complete response should be considered the most important prognostic factor for therapeutic trials in epidermoid carcinoma of the lung.

Antineoplastic Agents↗
PubMed1980

Therapy of advanced colorectal carcinoma with 5-fluorouracil and cyclophosphamide in combination with either CCNU or methotrexate.

In a prospective, randomized study a combination of 5-FU, Cyclophosphamide, and Methortrexate (FC-MTX) was compared to a similar combination (FC-CCNU) in which CCNU replaced Methotrexate. Of the 54 patients with metastatic colorectal carcinoma entered, 47 were evaluable. Toxicity was similar for the two regimens and was acceptable. No complete responses occurred. No difference in partial response (PR) 2/24 for FC-CCNU vs. 3/23 for FC-MTX, stable response 16/47 overall, or progressive disease 26/47 overall, was observed. Duration of PR was three to ten months. The overall median survival was six months, three months for non-responders and 11 months for responders. These drug combinations employing 5-FU do not improve upon the results reported with 5-FU alone in the treatment of metastatic colorectal carcinoma.

Adenocarcinoma↗
PubMed1980

Actinomycin D in the treatment of advanced breast cancer.

Actinomycin D is generally administered by serial low-dose injection over 5-10 days. Recent recognition of prolonged serum and tissue half-lives suggests that high-dose intermittent injecton should be equally effective and less toxic. An intermitten single dose schedule was selected for this phase II trial of actinomycin D in 23 patients with advanced breast cancer refractory to standard combination chemotherapy. The drug was given in doses of 0.75-1.5 mg/m2 at 2-week intervals or on days 1 and 8 of 28-day treatment cycles. One patient obtained a partial response with a duration of 5.7 months. Four patients experienced stabilization of advanced disease, with a mean duration of response of 6.4 months. Gastrointestinal toxicity occurred in 47% of patients and mild to moderate myelosuppression in 39%. We conclude that actinomycin D in this dosage and schedule has limited activity in advanced breast cancer. Higher doses might result in increased response rates but would be associated with greater toxicity.

Breast Neoplasms↗
PubMed1979

Written informed consent in patients with breast cancer.

One hundred breast cancer patients, 35 adjuvant and 65 advanced, were interviewed 0-24 months after the start of chemotherapy to assess their knowledge and perceptions of the purposes, risks and benefits of treatment. Prior to therapy, all had been given verbal explanations and had signed informed consent forms explicitly detailing drugs, objectives and possible adverse effects of therapy. Seventeen percent of adjuvant and 29% of advanced patients were unable to name any of their drugs. While most patients recognized distressing side effects such as nausea and hair loss, less than 50% were aware of the potentially lethal complications of infection and bleeding. While the purpose of adjuvant therapy was cure, only 29% of the adjuvant patients were aware of this. In contrast, 35% of the advanced patients incorrectly stated that they were told their therapy was potentially curative. Explanations given by a nurse in addition to a physician were better understood than those given by a physician alone. We conclude that, in spite of intensive efforts at improving informed consent procedures, current results are unsatisfactory.

Adult↗
PubMed1979

Improved survival of increased-risk myeloma patients on combined triple-alkylating-agent therapy: a study of the CALGB.

Two hundred fifty-two previously untreated evaluable patients with multiple myeloma were entered into a study testing a regimen of three intravenous alkylating agents, melphalan, cyclophosphamide, and carmustine (BCNU), given in combination (BCMP) against a regimen employing oral melphalan (MP). Both regimens included a tapering course of prednisone. Objective responses based on the Myeloma Task Force criteria were significantly more frequent in the group receiving BCMP. Survival for the entire group of BCMP-treated patients was not significantly better than that for MP-treated patients (p = 0.62). However, when the survival of the poor-risk (high tumor cell load) group of patients treated with BCMP was compared with the survival of the poor-risk (high tumor cell load) group of patients treated with MP, an improvement in survival attributable to BCMP therapy was seen (p = 0.049 and 0.02, respectively). In the good-risk (low and intermediate tumor cell load) group, BCMP treatment resulted in a trend toward poorer survival, but this did not achieve statistical significance (p = 0.080 and 0.23, respectively). These results indicate that optimal therapy in myeloma may be dependent on the extent of disease at the time of first treatment. Additional studies to explore the effects of treatment intensity and duration are needed in order to design improved myeloma treatment based on the patient's extent of disease.

Alkylating Agents↗