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Biomedical subjects

P B McCulloch

Publications and source records attributed to P B McCulloch.

At least 19 recordsLinked to original sources
PubMed1996

Randomized, double-blind, placebo-controlled trial comparing the response rates of carmustine, dacarbazine, and cisplatin with and without tamoxifen in patients with metastatic melanoma. National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: We designed and conducted a randomized, double-blind, placebo-controlled trial to compare the response rates and survival of patients with metastatic melanoma who received carmustine (BCNU), dacarbazine (DTIC), and cisplatin with tamoxifen, or the same chemotherapy with placebo. PATIENTS AND METHODS: Eligible patients with metastatic melanoma received either BCNU 150 mg/m2 intravenously (i.v.) on day 1, DTIC 220 mg/m2 i.v. daily on days 1 to 3 and on days 22 to 24, and cisplatin 25 mg/m2 i.v. daily on days 1 to 3 and on days 22 to 24 with placebo every 6 weeks, or the same chemotherapy with tamoxifen 160 mg orally daily for 7 days before chemotherapy and 40 mg orally daily throughout the remainder of the treatment cycle. Patients were treated on protocol for up to three cycles depending on the type of response. Assuming that a minimum increase in response rate of 20% would be necessary to conclude that tamoxifen conferred a clinically important benefit, we designed the study with an 80% chance of detecting that difference at the 5% level (two-sided). RESULTS: Between February 1992 and January 1995, 211 patients were accrued, 199 of whom were considered assessable for response and toxicity. The overall response rate was 21% in the placebo group and 30% in the tamoxifen group (P = .187). Complete and partial responses were 3% and 27%, respectively, for the tamoxifen group and 6% and 14%, respectively, for the placebo group. Poor performance status and liver involvement were associated with a reduced likelihood to respond to treatment. Major toxicities were similar in both groups with no statistically significant difference in the rates of deep vein thrombosis, pulmonary thromboembolus, grade 4 neutropenia, or grade 4 thrombocytopenia. CONCLUSION: These results demonstrate that the addition of high doses of tamoxifen to this chemotherapy regimen does not increase the response rate compared with chemotherapy alone in unselected patients with metastatic melanoma.

Adult↗
PubMed1992

Randomized clinical trial to assess the effectiveness of breast irradiation following lumpectomy and axillary dissection for node-negative breast cancer.

BACKGROUND: Although the conservation management of breast cancer has become a routine method of treatment in most centers, there is still considerable controversy surrounding the ultimate minimum treatment required for node-negative breast cancer to achieve adequate local control. PURPOSE: Our purpose was to assess the value of breast irradiation in reducing breast relapse following conservation surgery for node-negative breast cancer. We attempted to define low-risk groups of women for breast and distant site relapse (i.e., recurrence outside the breast) who might be spared breast irradiation or adjuvant systemic therapy. METHODS: Eight hundred thirty-seven patients were randomly assigned to receive radiation therapy or no radiation therapy following lumpectomy and axillary dissection for node-negative breast cancer. RESULTS: Breast irradiation reduced relapse in the breast from 25.7% in the controls to 5.5% in the irradiated patients. There was no difference in survival between the two groups (median follow-up, 43 months). A low-risk group (less than 5% chance of relapse in the breast without irradiation) could not be defined. Tumor size (greater than 2 cm), age (less than 40 years), and poor nuclear grade were important predictors for breast relapse. Age (less than 50 years) and poor nuclear grade were important predictors for mortality. The presence of ductal carcinoma in situ did not predict breast relapse. CONCLUSIONS: Breast irradiation significantly reduces breast relapse, but it does not influence survival. Important predictors of breast relapse are age, tumor size, and nuclear grade, but not the presence of ductal carcinoma in situ. Age and, in particular, nuclear grade predict survival. IMPLICATIONS: Further follow-up may define an acceptable low-risk group for breast relapse. Until then, we recommend that all patients receive breast irradiation. Systemic adjuvant therapy should be considered for patients with poor nuclear grade tumors.

Age Factors↗
PubMed1991

Premortem and postmortem measurement to study structure with function: a human brain collection.

Basic issues concerning structure-function relationships in the normal human brain remain unresolved. For example, it is not known what structural basis may underlie the functional specialization of the two cerebral hemispheres or the variation in cognitive ability among people. The study of the general principles of gross and microscopic brain structure in relation to behavior requires direct postmortem study of samples of brain specimens from cognitively normal people for whom quantitative measures on neuropsychological scales are available. No such work has been reported. Although conceptually simple, such research is administratively complex. We present here an approach to the study of structure-function relationships involving postmortem measurements of the human brain. Our subjects were cancer patients who were ambulatory but had a poor prognosis. They agreed to participate in research involving both premortem neuropsychological testing on prospectively selected measures, and, in the event of death, an autopsy and subsequent neuroanatomical study. We describe the essential features of our method including the neuropsychological testing and processing of brain specimens, document the method's feasibility by reporting the number of subjects recruited and autopsies obtained, and discuss the possible usefulness of such research as a prototype for other studies and the various issues such research raises. The present collection of brain specimens and associated medical and neuropsychological documentation is a unique resource and, accordingly, tissue and associated documentation will be made available as a resource to neuroscientists for use in other basic research or as control cases in studies of neuropsychiatric disease.

Adult↗
PubMed1991

Improved survival in patients with poor-prognosis malignant melanoma treated with adjuvant levamisole: a phase III study by the National Cancer Institute of Canada Clinical Trials Group.

Five hundred forty-three patients with completely resected malignant melanoma who were considered to have a significant risk of developing recurrent disease were randomized to one of four study groups. One group received levamisole 2.5 mg/kg on 2 consecutive days weekly for 3 years, a second group received bacillus Calmette-Guérin (BCG) for 3 years. A third group alternated 8-week courses of BCG and levamisole for 3 years and a fourth group underwent clinical assessment at the same frequency as the three treatment groups. The median duration of follow-up is 8.5 years. The percentage of reduction in the death rate and the recurrence rate in the treatment groups compared with the control group was calculated using the Cox proportional hazards model and adjusted for age, sex, and stage as covariants. The patients treated with levamisole were estimated to have a 29% reduction in both the death rate (P = .08) and the recurrence rate (P = .09) compared with patients receiving no further treatment. Fifty-five patients discontinued levamisole early because of gastrointestinal intolerance or arthralgia, myalgia, fever, and immune leukopenia. The patients treated with BCG alternating with levamisole experienced a 10% reduction in the death rate and a 6% reduction in the recurrence rate, and the patients treated with BCG alone experienced a 4% reduction in the death rate and a 3% increase in the recurrence rate compared with the control group. The degree of improvement experienced by the patients that were treated by levamisole is of sufficient magnitude to warrant further investigation of this dose of levamisole as adjuvant treatment in patients with melanoma.

Adolescent↗
PubMed1989

Systemic adjuvant therapy for node-negative breast cancer.

In response to recent advice from the US National Cancer Institute concerning the use of systemic adjuvant therapy for node-negative breast cancer we reviewed the literature and found that several studies have shown evidence of a disease-free, but not an overall, survival advantage for treated patients. The benefits have been modest and may not outweight the cost and toxic effects of such therapy. Routine use does not seem to be justified. Factors must be identified to differentiate between patients at low risk and those at high risk. It should then be determined if adjuvant therapy is truly beneficial in those who are at high risk.

Antineoplastic Agents↗
PubMed1984

Sensitivity of human carcinoma cell lines to lysis by blood natural killer cells correlating with surface expression of carcinoembryonic antigen.

The HCT-8R clone of the HCT-8 human colon tumor line, which expresses increased quantities of carcinoembryonic antigen (CEA) on its surface, was discovered to have an enhanced susceptibility to lysis by natural killer (NK) cells in human peripheral blood. This increase in susceptibility to lysis by peripheral blood mononuclear cells was not explained by stimulation of interferon release by HCT-8R cells but rather was found to be attributable to an increased susceptibility of HCT-8R cells to lysis by those NK cells that bind to sheep erythrocytes (E-RFC). Cold target competition experiments and single-cell assay for cytotoxic cells suggested that the presence of surface CEA did not increase lysis of HCT-8R by facilitating "recognition" by E-RFC-type cytotoxic cells but by rendering HCT-8R cells more susceptible to the lytic mechanism of NK cells. The magnitude of expression of surface CEA by a variety of human carcinoma cell lines with a few exceptions and subclones of HCT-8 also correlated with increased susceptibility to lysis by blood mononuclear cells. The possible clinical significance of these findings was discussed.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1982

Absence of melanoma specificity in the reactivity of melanoma patients' sera with cultured allogeneic melanoma cell lines.

While patients with melanoma are known to produce antibodies against melanoma cells, the tumor specificity of these reactions has not been well documented. Using the sensitive mixed hemadsorption assay we have identified antibody against one or more of nine different cultured melanoma cell lines in only nine of 48 patients with melanoma. Reactivity against melanoma cell lines was seen only in females, 9/27 versus 0/21 males. The strongest melanoma reactivity was seen in sera which also contained lymphocytotoxic antibody. The reactivity was not melanoma specific because it could be removed by absorption either with pooled platelets, nonmelanoma tumor cells or in two cases, by both. We conclude that the occurrence of specific antimelanoma antibodies against common or shared surface melanoma associated antigens is an uncommon event in melanoma patients not receiving specific active immunotherapy. The clinical significance of the observed reactivity and whether it is directed against cancer associated determinants, fetal antigens, or normal tissue or histocompatibility antigens requires further study.

Antibodies, Neoplasm↗
PubMed1980

Correlation of elevated C1q binding activity and carcinoembryonic antigen levels with clinical features and prognosis in bronchogenic carcinoma.

The presence of immune complexes and carcinoembryonic antigen (CEA) was investigated in 50 patients with bronchogenic carcinoma at the time of and/or following diagnostic or definitive surgery. Immune complexes were measured by the C1q binding test and CEA by the Z gel method and elevations defined as values in excess of 2 S.D. above the normal mean, greater than or equal to 9.2% for C1q binding activity (C1q-BA) and greater than or equal to 5.0 ng/ml for CEA. The overall incidence of elevated values was 30.7% for C1q-BA and 34.2% for CEA. There was a greater incidence of elevated values of C1q-BA among patients with clinically evident disease. The differences with respect to CEA elevation were not significant due to the fact that 6 of 9 samples with elevated CEA values obtained from patients with no evident disease were in fact associated with the presence of clinically undetectable disease in these patients. Elevation of C1q-BA and CEA beyond the immediate postoperative period was predictive of a significantly shorter median survival time. The most significant differences in survival time were seen between patients with normal values for C1q-BA and CEA and those with elevations of one or both parameters, 6.0 vs. 19.5 months (p less than 0.001). Elevation of either parameter during the immediate pre- and postoperative period was not predictive of a poor survival. In terms of clinical application, it appears that CEA estimation had the best predictive value but that the addition of C1q-BA measurement may provide additional prognostic information, particularly in patients who do not have elevated CEA values.

Adenocarcinoma↗
PubMed1980

The relevance of platelet and fibrinogen kinetics and coagulation studies to extent of disease and performance status in patients with adenocarcinoma.

In this study of 18 cancer patients, results of laboratory evaluation of a "hypercoagulable state" have been correlated with the extent of the disease and the functional activity of the patients. Most coagulation tests were normal. Higher levels of serum fibrinogen degradation products were associated with wider dissemination of disease. Fibrinogen survival time (t1/2) was shorter in patients with extensive disease than in those with less extensive disease (P < 0.05); platelet t1/2 was also shorter in the former group, though not significantly. Coexistence of severest physical disability and extensive disease was associated with the most marked reduction of platelet and fibrinogen t1/2. There was little correlation between platelet and fibrinogen t1/2, thus suggesting independent mechanisms of destruction of the two blood components. We suggest that future studies of hemostatic changes in cancer patients should include assessment of impairment of physical performance of the patients, as well as the extent of the tumor.

Adenocarcinoma↗
PubMed1979

Application of tumor marker analysis to patients with lung cancer.

Measurement of Clq-BA and CEA levels in patients with lung cancer may provide additional information about their clinical status discriminating between disease free patients and those with residual disease. Post-operative determination of Clq-BA and CEA levels may assist in defining patients which have poor prognosis. Preliminary evidence suggests that Clq-BA measurement may provide additional prognostic information in a small group of patients with normal CEA values. Finally, the presence of elevated Clq-BA in tumor bearing patients is of fundamental importance in the biology of cancer as it suggests that there are some tumor associated antigens which provoke the production of antibody in the host with the resultant formation of circulating immune complexes. The definition of the nature of the antigen in these immune complexes awaits further study.

Carcinoembryonic Antigen↗
PubMed1978

Measurement of carcinoembryonic antigen in patients with bronchogenic carcinoma.

Estimation of CEA levels by the Z-gel method indicates that smokers, patients with limited lung cancer and patients with extensive lung cancer have higher values than nonsmoking controls. The CEA levels within each group are significantly different from one another. Use of CEA estimation for diagnostic purposes is limited because of the considerable overlap between normal controls and patients with cancer, the relatively low incidence of elevated values in patients with limited disease and the high incidence of false negatives (20%) even in patients with extensive disease. Elevated CEA values are associated with a poor prognosis and could be of clinical value as an addition to clinical staging to determine survival particularly for patients with extra-thoracic disease. Persistently high values in patients deemed clinically disease-free postoperatively are indicative of residual disease and a poor prognosis. If and when effective therapy for bronchogenic carcinoma becomes available, monitoring of CEA values may be useful in some patients as an early indication of release. Further studies are required to determine if the extraordinarily poor prognosis associated with marked elevations of CEA may be used as an additional criterion of inoperability in such patients.

Carcinoembryonic Antigen↗
PubMed1978

Clinical response and plasma levels of 5-fluorouracil in patients with colonic cancer treated by drug infusion.

Concentrations of 5-fluorouracil (FU) were measured in the plasma of patients receiving i.v. infusions of the drug for 5 days as treatment for adenocarcinoma of the gastrointestinal tract. Concentrations of FU varied widely in many patients. Concentration of drug X time of infusion (C X t values) were calculated. Patients showing a partial response or stabilization of disease had significantly higher C X t values than non-responders. Methyl CCNU did not affect the C X t values of FU. Determination of the plasma concentration of FU would allow the dose of the drug to be adjusted to maintain high concentrations of FU in the plasma. Our data suggest that such high concentrations would increase the response rate in this disease.

Adenocarcinoma↗
PubMed1977

Recurrent malignant melanoma: effect of adjuvant immunotherapy on survival.

Twenty-nine patients referred consecutively to a cancer clinic because of recurrent metastatic malignant melanoma were given 5 mg of Connaught Laboratories bacillus Calmette-Guérin (BCG) by multiple cutaneous puncture at weekly and later at monthly intervals. Eight were also treated with autologous tumour vaccine and three with intralesional BCG. This group was compared with a retrospective control group of 54 patients treated with surgery and radiotherapy alone after recurrence. Prognostic features such as site of primary and of first metastasis, disease-free interval, age and sex were similar in the two groups. However, the median survival from the time of first recurrence was 12 months in the control group but 21 months in the BCG-treated group. The major improvement was in patients with disease limited to the regional lymph nodes: the median survival was 16 months in the control group but over 32 months in the BCG-treated group. Autologous tumour vaccine appeared to have no effect on survival. Serial testing of immunocompetence did not offer any prognostic advantage, although the results of some tests correleated well with extent of disease.

BCG Vaccine↗
PubMed1976

Cellular morphology of human malignant melanoma in primary culture.

Early monolayer outgrowths of cells from human cutaneous malignant melanomas mostly derived from metastatic lesions were examined microscopically. Cells resembling the two dendritic types of melanoma previously described in the established lines could readily be recognized. Of 22 specimens, 14 consisted of cells with a triangular dendritic morphology, four had both triangular and elongated dendritic morphology, and one had a cuboidal morphology. The remaining three specimens showed only fibroblastic outgrowths. It is concluded that cells with a triangular dendritic morphology are either the most common type of the secondary cutaneous melanomas, or alternately the most adaptable to the present culture conditions. An association of a more favorable prognosis with the homogeneous triangular dendritic cell type is noted.

Cell Division↗