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M Trudeau

Publications and source records attributed to M Trudeau.

At least 19 recordsLinked to original sources
PubMed2005

Neoadjuvant taxanes in the treatment of non-metastatic breast cancer: a systematic review.

In recent years the role of neoadjuvant (primary, preoperative) chemotherapy has undergone rapid progress. Initially, neoadjuvant chemotherapy use was limited to those patients with inoperable locally advanced breast cancer in an attempt to try to down-size the tumour to make effective surgery possible. The advent of more effective chemotherapy regimens has led to an increased use of neoadjuvant therapy to shrink potentially operable tumours to allow for breast conservation when a mastectomy would have been required previously. While neoadjuvant treatment for operable tumours has indeed allowed increased rates of breast conserving surgery, it has not yet demonstrated any survival benefit over standard postoperative anthracycline-based chemotherapy. Echoing the evolution of taxane based chemotherapy from the metastatic setting through to the adjuvant situation, there has been increased interest in the role of taxanes in neoadjuvant regimens. The use of taxane-based therapies in this setting has so far shown improvements over more standard regimens in terms of clinical response rates, breast conservation, pathologic response rates, disease free survival, and overall survival. The aim of this review is to systematically summarize and interpret the results of published randomized controlled trials of neoadjuvant taxane chemotherapy for women with non-metastatic breast cancer.

Breast Neoplasms↗
PubMed2003

Sodium channels SCN1A, SCN2A and SCN3A in familial autism.

Autism is a psychiatric disorder with estimated heritability of 90%. One-third of autistic individuals experience seizures. A susceptibility locus for autism was mapped near a cluster of voltage-gated sodium channel genes on chromosome 2. Mutations in two of these genes, SCN1A and SCN2A, result in the seizure disorder GEFS+. To evaluate these sodium channel genes as candidates for the autism susceptibility locus, we screened for variation in coding exons and splice sites in 117 multiplex autism families. A total of 27 kb of coding sequence and 3 kb of intron sequence were screened. Only six families carried variants with potential effects on sodium channel function. Five coding variants and one lariat branchpoint mutation were each observed in a single family, but were not present in controls. The variant R1902C in SCN2A is located in the calmodulin binding site and was found to reduce binding affinity for calcium-bound calmodulin. R542Q in SCN1A was observed in one autism family and had previously been identified in a patient with juvenile myoclonic epilepsy. The effect of the lariat branchpoint mutation was tested in cultured lymphoblasts. Additional population studies and functional tests will be required to evaluate pathogenicity of the coding and lariat site variants. SNP density was 1/kb in the genomic sequence screened. We report 38 sodium channel SNPs that will be useful in future association and linkage studies.

Autistic Disorder↗
PubMed2001

Synthesis and electronic properties of low-dimensional bis(benzene) vanadium reduced mesoporous niobium oxide composites.

The first bis(benzene) vanadium mesoporous niobium oxide composite was synthesized and characterized. The XRD pattern of this material shows a peak (100) centered at 45 A, identical to that of starting material. The nitrogen adsorption and desorption analyses of this material exhibit a slight decrease of BET surface area from 580 m(2) g(-1) to 467 m(2) g(-1) and a concomitant decrease in pore size and volume from 28 A and 0.500 cm(3) g(-1) to 25 A and 0.363 cm(3) g(-1), respectively. The powder EPR spectrum shows eight lines which can be assigned to (51)V from bis(benzene) vanadium as well as other resonances that can be assigned to the corresponding cation. The presence of two or more organometallic vanadium species was further confirmed by UV, (1)H-MAS NMR, and XPS methods. Broadened and shifted Nb 3/2, 5/2 peaks were also observed, providing further evidence that the mesoporous transition metal oxide framework was reduced by the organometallic. SQUID magnetometer measurements on this material show paramagnetic behavior with a small contribution of spin glass behavior. The conductivity of this material was 10(-4) ohm(-1) cm(-1), significantly greater than that measured for the analogous bis(benzene) chromium composite previously studied. Since alkali-metal reduced mesoporous niobium oxide materials are insulating, this conductivity was attributed to the low-dimensional bis-arene vanadium phase in the pores and rationalized according to the balance between the Hubbard potential and the bandwidth estimated for the relevant organometallic species. A bis-1,3,5-tri-tert-butylbenzene yttrium composite was also synthesized; however, complete loss of ligand upon reduction of the mesostructure was observed, indicating that this dopant behaves more like an alkali naphthalene reagent in its reactions with mesoporous niobium oxide than other bis(arene) complexes investigated by our group.

Journal Article↗
PubMed2001

Synthesis and characterization of a new family of electroactive alkali metal doped mesoporous Nb, Ta, and Ti oxides and evidence for an Anderson transition in reduced mesoporous titanium oxide.

Recently we reported that mesoporous niobium oxide can be chemically reduced by Na-naphthalene while fully retaining its mesostructure. This was the first report of a molecular sieve acting as a stoichiometric electron acceptor. Herein we expand on the initial work by presenting a detailed study on Li-, Na-, K-, Rb-, and Cs-reduced samples of mesoporous Nb oxide, as well as Li-reduced mesoporous Ta and Ti oxides. While the Nb- and Ta-based materials fully retained their structure on reduction as determined by X-ray diffraction (XRD) and nitrogen adsorption, the Li-reduced Ti material retained high surface area and narrow pore size distribution, but lost its diffraction pattern, indicating an increased level of disorder in this material. X-ray photoelectron spectroscopy (XPS) and UV-visible reflectance spectroscopy revealed that all reduced mesoporous oxides studied have a similar electronic structure, corresponding to the presence of a disordered impurity band in the material lying between the valence band and the conduction band. Electron paramagnetic resonance (EPR) studies suggest that the electron in this impurity level is unpaired and best described as a free electron, only loosely bound to the alkali or transition metal. SQUID magnetometry showed that all reduced materials are paramagnetic, further confirming the presence of unpaired electrons in the structure. All materials in this study were insulating with the exception of the Li-reduced mesoporous Ti material, which was highly conducting, possibly due to an Anderson transition. Electrochemical studies on the unreduced mesoporous oxides demonstrated that while the Ta and Nb materials are capacitors with only a small degree of reversible electrochemical behavior in the bulk sample, the Ti material was an electrical conductor with fully reversible redox behavior.

Journal Article↗
PubMed2001

Endometrial evaluation with transvaginal US and hysterosonography in asymptomatic postmenopausal women with breast cancer receiving tamoxifen.

PURPOSE: To determine performance characteristics of transvaginal ultrasonography (US) and hysterosonography for diagnosing endometrial abnormality in asymptomatic postmenopausal women with breast cancer receiving tamoxifen. MATERIALS AND METHODS: The authors prospectively examined 138 women receiving tamoxifen by using transvaginal US, hysterosonography, and office hysteroscopy. The combined hysteroscopic-histopathologic diagnosis was the reference standard. Sensitivity, specificity, positive and negative predictive values, and likelihood ratios of transvaginal US and hysterosonography were calculated. RESULTS: All 138 women underwent transvaginal US; 104, successful hysterosonography; and 117, successful hysteroscopy. Uterine abnormality was present in 47 (40.2%) of 117 women: 45 with polyps and two with submucosal fibroids. Receiver operating characteristic curve analysis revealed 6 mm to be the optimal endometrial thickness cutoff for diagnosing endometrial abnormalities. When a thickness greater than 6 mm or a focal endometrial finding was considered abnormal, transvaginal US had a sensitivity of 85.1% and a specificity of 55.7%. In 92 women who completed transvaginal US, hysterosonography, and hysteroscopy, hysterosonography was more specific (79.2%; P =.008) but not significantly more sensitive (89.7%; P =.508) than transvaginal US. When women with abnormal transvaginal US findings were further examined with hysterosonography, the sequential combination of transvaginal US and hysterosonography was more specific (77.1%) than transvaginal US alone (P <.001), without a significant decrease in sensitivity (78.7%; P =.25). CONCLUSION: In asymptomatic postmenopausal women receiving tamoxifen, 6 mm is the optimal endometrial thickness cutoff for diagnosing endometrial abnormalities with transvaginal US. Further examination with hysterosonography can improve specificity by reducing the high false-positive rate of transvaginal US.

Antineoplastic Agents, Hormonal↗
PubMed2001

Epirubicin in combination with the taxanes.

The anthracyclines, and doxorubicin in particular, have been the most widely used drugs for advanced and metastatic breast cancer. Epirubicin shares the same spectrum of antitumor activity as doxorubicin, however, a therapeutic advantage of epirubicin is the higher cumulative dose at which the anthracycline-induced cardiotoxicity becomes clinically evident. The taxanes have quickly been established as important chemotherapeutic agents in the armamentarium of drugs to treat breast cancer. Evaluation of the combination of anthracyclines with the taxanes was a logical research step with the aim to improve overall outcome and, potentially, survival of breast cancer patients. The findings of a high rate of cardiotoxicity from the initial phase II trials of combination doxorubicin/paclitaxel led investigators to alter the anthracycline and the taxane component of the combination by substitution with epirubicin and/or docetaxel, respectively. Results of phase I and II clinical trials with epirubicin plus a taxane shows a high level of antitumor activity, with the absence of significant cardiac toxicity and limited severity of other nonhematologic toxicities, thus making the epirubicin and taxane combinations highly attractive. Additional studies in metastatic breast cancer patients, for whom prolonged administration with an anthracycline is of potential clinical benefit, are underway. Evaluation of epirubicin and taxane combinations in the adjuvant setting are warranted and ongoing where prevention of cardiotoxicity is as important as efficacy.

Antibiotics, Antineoplastic↗
PubMed2000

X-ray photoelectron spectroscopy and magnetic studies on the effect of pore size, wall thickness, and wall composition on superparamagnetic cobaltocene mesoporous Nb, Ta, and Ti composites.

Recent results in our group demonstrated that mixed oxidation state mesoporous niobium oxide cobaltocene composites display superparamagnetism at certain composition ratios. This was the first report of superparamagnetism in nanoscale molecular ensembles. A series of mesoporous niobium oxide materials were synthesized in order to understand the role of pore size and thickness of the walls in the mesostructure on the magnetic properties. Mesoporous Ti oxide and Ta oxide composites were also synthesized in order to investigate the effect of changing the wall composition on the magnetic properties of this new series of materials. All samples were characterized by X-ray diffraction, nitrogen adsorption, ultraviolet spectroscopy, X-ray photoelectron spectroscopy, scanning electron microscopy, and superconducting quantum interference device magnetometry. The results of this study showed that variation of wall thickness or pore size in the Nb system had little effect on the properties and that superparamagnetism most likely arises from mixed oxidation state cobaltocene grains residing in the individual pores and not from the free electrons in the mesostructure or much larger domains. The Langevin function was applied to the isothermal magnetic data from the Nb composites and gave mean superparamagnetic particle sizes of ca. 14 nm in each system. The Co(II) to Co(III) ratios in these materials were approximately 1:1. The Ti and Ta materials showed no sign of superparamagnetism and only very low levels of neutral cobaltocene in the pores. This suggests that a critical amount of cobaltocene is required to bring about superparamagnetic behavior.

Journal Article↗
PubMed2000

Phase III comparative study of vinorelbine combined with doxorubicin versus doxorubicin alone in disseminated metastatic/recurrent breast cancer: National Cancer Institute of Canada Clinical Trials Group Study MA8.

PURPOSE: This phase III study was performed to determine the superiority of doxorubicin (DOX) and vinorelbine (VNB) (arm 1) versus DOX alone (arm 2) in metastatic breast cancer (MBC) for overall survival (OS), time to treatment failure (TTF), toxicity, and quality of life (QOL). PATIENTS AND METHODS: Three hundred three patients were randomized to DOX 50 mg/m(2) intravenously (IV) on day 1 and VNB 25 mg/m(2) IV on days 1 and 8 (arm 1) or DOX 70 mg/m(2) IV on day 1 (arm 2). Both regimens were given every 3 weeks until a cumulative DOX dose of 450 mg/m(2). After 16 of the first 65 randomized patients experienced febrile neutropenia (FN), the doses were reduced to DOX 40 mg/m(2) on day 1 and VNB 20 mg/m(2) on days 1 and 8 versus DOX 60 mg/m(2) on day 1. Eligible patients were vinca alkaloid and anthracycline naive. Chemotherapy was first-line or second-line for MBC. RESULTS: Three patients were ineligible. Thus, 300 patients were assessable for toxicity and to determine time to disease progression (TTP), TTF, and OS. Two hundred eighty-nine patients were assessable for response, and 99 responders were assessable for response duration (RD). The response rates, QOL, and median RD, TTP, and TTF were not significantly different between the arms. Median OS was 13.8 months for arm 1 versus 14.4 months for arm 2 (P =.4). Grade 3 or 4 granulocytopenia was equivalent in both arms but more grade 3/4 neurotoxicity, mild venous toxicity, and FN were seen on arm 1. CONCLUSION: The survival with DOX and VNB is not superior to DOX alone in MBC.

Adult↗
PubMed1999

Adjuvant treatment and onset of menopause predict weight gain after breast cancer diagnosis.

PURPOSE: Weight gain is common during the first year after breast cancer diagnosis. In this study, we examined clinical factors associated with body size at diagnosis and weight gain during the subsequent year. PATIENTS AND METHODS: An inception cohort of 535 women with newly diagnosed locoregional breast cancer underwent anthropometric measurements at baseline and 1 year. Information was collected on tumor- and treatment-related variables, as well as diet and physical activity. RESULTS: Mean age was 50.3 years; 57% of women were premenopausal. Mean baseline body mass index (weight [kg] divided by height [m] squared) was 25.5 kg/m2. Overall, 84.1% of the patients gained weight. Mean weight gain was 1.6 kg (95% confidence interval, 1.2 to 1.9 kg), 2.5 kg (95% confidence interval, 1.8 to 3.2 kg) in those receiving chemotherapy, 1.3 kg (95% confidence interval, 0.7 to 1.8 kg) in those receiving tamoxifen only, and 0.6 kg (95% confidence interval, 0.01 to 1.3 kg) in those receiving no adjuvant treatment. Menopausal status at diagnosis (P = .02), change in menopausal status over the subsequent year (P = .002), axillary nodal status (P = .009), and adjuvant treatment (P = .0002) predicted weight gain in univariate analysis. In multivariate analysis, onset of menopause and administration of chemotherapy were independent predictors of weight gain (all P < or = .05). Caloric intake decreased (P < .01) and physical activity increased (P < .05) during the year after diagnosis; these factors did not explain the observed weight gain. CONCLUSION: Weight gain is common after breast cancer diagnosis; use of adjuvant chemotherapy and onset of menopause are the strongest clinical predictors of this weight gain.

Age of Onset↗
PubMed1999

Risk of menopause during the first year after breast cancer diagnosis.

PURPOSE: Premenopausal women with breast cancer often enter a premature menopause during initial treatment of their malignancy, with resulting loss of childbearing capacity, onset of menopausal symptoms, and subsequent prolonged exposure to long-term risks of menopause. Adjuvant therapy is believed to contribute to this early menopause. PATIENTS AND METHODS: One hundred eighty-three premenopausal women with locoregional breast cancer (tumor-node-metastasis staging system classification, T1-3 N0-1 M0) who had undergone surgical treatment and provided information on menopausal status at diagnosis and 1 year later were enrolled. Systemic adjuvant therapy was recorded. Univariate and multivariate predictors of menopause were examined. RESULTS: Age, weight gain, tumor stage, nodal stage, and systemic adjuvant therapy (chemotherapy, tamoxifen) were all significant univariate correlates of menopause. In multivariate analysis, age, chemotherapy, and hormone therapy (tamoxifen) made significant independent contributions to the onset of menopause. CONCLUSION: Age and systemic chemotherapy are the strongest predictors of menopause in women with locoregional breast cancer. They independently contribute to menopause. A graphic representation of our multivariate model allows an estimation of risk of menopause according to patient age and planned adjuvant treatment, and it may facilitate clinical decision-making.

Adult↗
PubMed1999

Liver metastasis: comparison of 2 methods for reporting of disease in patients receiving chemotherapy.

OBJECTIVE: To compare bidimensional measurements with direct volumetry in the reporting of disease in patients with liver metastases who are receiving chemotherapy. PATIENTS AND METHODS: Ten patients (6 men and 4 women) receiving chemotherapy were included. A total of 37 contrast-enhanced abdominal computed tomographic (CT) scans, forming 26 pairs of studies, were evaluated retrospectively by 2 independent reviewers. One reviewer recorded bidimensional measurements from hard-copy films, and the other recorded volumetric measurements at the CT console. All measurements were analysed before and after application of a 5% variation interval. RESULTS: Reporting of disease was initially discordant in 5 (19%) of the 26 paired examinations. After application of a 5% variation interval, 9 cases (35%) were discordant. When borderline results (type of response modified by 5% variation) were excluded, 4 discordant cases (20%) remained. All but 1 case showed progressive disease with bidimensional measurements and no change at volumetry. The presence of a new lesion affected reporting in only 1 case. CONCLUSION: The 2 methods of reporting disease are not interchangeable. We believe that volumetric measurements are more representative of tumour burden than bidimensional measurements. However, acquisition of nonhelical data may be a pitfall in volumetric measurements. The increasing availability of helical CT technology should resolve this issue.

Antineoplastic Agents↗
PubMed1999

Evaluation of HER-2/neu (erbB-2) status in breast cancer: from bench to bedside.

Molecular alterations in breast cancer are being incorporated into the development of new treatment strategies. The HER-2/neu oncogene has been extensively investigated as a prognostic factor and recently as a predictor of response to chemotherapy or endocrine therapy. The development of a humanized anti-HER-2 monoclonal antibody (Herceptin) and the encouraging results obtained in the treatment of patients with HER-2 overexpressing metastatic breast cancer with this antibody have resulted in renewed interest in HER-2/neu. This article reviews the current knowledge of HER-2/neu both as a prognostic and a predictive factor. Problems associated with the standardization of the methodology for assessing HER-2/neu status and clinically significant cut-off points are addressed.

Antibodies, Monoclonal↗
PubMed1998

On my doorstep.

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Attitude of Health Personnel↗
PubMed1998

Phase II study of dexverapamil plus anthracycline in patients with metastatic breast cancer who have progressed on the same anthracycline regimen.

The purpose of this study is to evaluate whether metastatic breast cancer that has progressed on an anthracycline-containing drug regimen will subsequently respond to that identical regimen if dexverapamil, a modulator of P-glycoprotein-mediated drug resistance, is given concomitantly. Eligible patients received 180 mg/m2 dexverapamil every 6 h for 15 doses with the anthracycline administered 30 min after the seventh dose. Blood for dexverapamil levels was drawn before and 30 min after this dose. When possible, biopsies were obtained to measure mdr-1 expression by reverse transcription-PCR and by image cytometry. Of the 21 patients entered onto the trial, 20 were evaluable for response. There were two partial responses (10%) that both lasted for 6 months, and two additional patients had stable disease. Seven patients had asymptomatic cardiotoxicity consisting of hypotension (24%), bradycardia (5%), or prolongation of the P-R interval (14%). Two patients developed acute congestive heart failure, one on dexverapamil and one 10 days after stopping it. Dexverapamil did not seem to increase anthracycline toxicity. The median trough dexverapamil plus norverapamil level on day 3 was 1110 ng/ml (range, 186-3385 ng/ml), and the median peak level was 2164 ng/ml (range, 964-8382 ng/ml). There was poor correlation between reverse transcription-PCR and image cytometry for the level of mdr-1 expression. Because dexverapamil has been shown to affect doxorubicin pharmacokinetics subsequent to the initiation of this trial, it cannot be concluded that the responses seen were necessarily due to P-glycoprotein inhibition. Additional studies are necessary to determine whether mdr-1 modulators can reverse clinical drug resistance in breast cancer patients. The intrinsic cardiotoxicity of dexverapamil makes it less suitable for such studies than several other available agents.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Clinical behavior of untreated axillary nodes after local treatment for primary breast cancer.

BACKGROUND: The purpose of this study was to examine the rate of axillary failure in patients with primary breast cancer treated without axillary dissection or radiation and to determine what factors may be associated with axillary failure. METHODS: We studied 112 patients with invasive breast cancer treated for primary disease with breast-conserving surgery without axillary dissection or radiation to the breast or axilla, accrued between 1977 and 1986. Data for these patients were prospectively gathered for a research database and reviewed retrospectively to determine axillary failure. The effects of age, tumor size, estrogen receptor (ER) status, progesterone receptor (PgR) status, histologic grade, nuclear grade, and tumor emboli on time to axillary failure were examined. RESULTS: The median follow-up was 9.6 years. There were 26 axillary recurrences, resulting in a 10-year actuarial nodal control rate of 72%. Patients with nodal failure proceeded to axillary dissection with minimal morbidity. In both univariate and multivariate analyses, only tumor size was significantly associated with axillary failure (p = 0.04 and p = 0.06, respectively). CONCLUSIONS: This study demonstrates a significant effect of tumor size on axillary failure and a reasonable rate of local control in small tumors. Further research should examine the utility of axillary dissection in women with small breast cancers.

Actuarial Analysis↗
PubMed1996

Stereoselective pharmacokinetics of ifosfamide and its 2- and 3-N-dechloroethylated metabolites in female cancer patients.

The pharmacokinetics of the R and S enantiomers of ifosfamide (IFF) and of its 2- and 3-N-dechloroethylated metabolites (2-DCE-IFF and 3-DCE-IFF) were investigated in 14 cancer patients treated with a 3-h infusion of (R,S)-IFF (3 g/m2) with mesna uroprotection. An enantioselective gas chromatographic-mass spectrometric (GC-MS) assay was used to determine the concentrations in plasma and urine. The AUCs of (R)-IFF were significantly larger than those of (S)-IFF (2480 +/- 200 vs 1960 +/- 150 microM.h). The terminal half-lives (7.57 +/- 0.99 h) and mean residence times (11.17 +/- 1.10 h) of (R)-IFF were significantly longer than those of (S)-IFF, 6.03 +/- 0.82 h and 9.37 +/- 0.88 h, respectively. The mean volume of distribution at steady rate of (R)-IFF (25.68 +/- 0.80 l/m2) was slightly smaller than that of (S)-IFF (27.35 +/- 0.89 l/m2). While the renal clearances of (R)-IFF and (S)-IFF were similar, the nonrenal clearance was significantly lower for (R)-IFF (30.20 +/- 2.70 vs 41.40 +/- 3.55 ml/m2 per min) as was total clearance (41.52 +/- 2.90 vs 52.37 +/- 3.75 ml/m(2) per min). The AUC values for all of the DCE metabolites from (S)-IFF were significantly greater than those from (R)-IFF with 47% of the measured AUC accounted for by DCE from (S)-IFF compared to only 20% for (R)-IFF. Therefore, the enantioselective difference in IFF elimination can be partially explained by differences in N-dechloroethylation.

Antineoplastic Agents, Alkylating↗
PubMed1995

A phase I study of recombinant human interferon alpha-2b combined with 5-fluorouracil and cisplatin in patients with advanced cancer.

To determine the maximum tolerated dose (MTD) of escalating doses of interferon-alpha-2b (IFN, Intron A) with 5-fluorouracil (5-FU) and cisplatin (DDP) in patients with advanced cancer, 15 patients were accrued between May 1990 and July 1991. Primary sites were unknown (3), colorectal (3), head and neck (2), lung (2), gynecologic (1), gallbladder (1), sarcoma (1), anal canal (1) and pancreas (1). IFN was given s.c. on days 1-5 and then three times weekly with DDP (75 mg/m2, day 1) and 5-FU [750 mg/m2, days 1-5, continuous infusion (CI) on a 28-day cycle. The first two patients treated at level I (3 x 10(6) U/m2 s.c.) experienced possible neurotoxic deaths [massive cerebrovascular accident (CVA) and metabolic encephalopathy], and patient 3 had a grade 4 toxicity of performance status decline. Analysis of these events led us to exclude the enrollment of patients on i.v. morphine and of those with prior exposure to DDP. This resulted in grade 3 toxicity in terms of nausea, vomiting, fatigue and leukopenia but in no further CNS event. All patients were evaluable for toxicity but only ten were evaluable for response. Only two partial responses were seen, one in a patient with an unknown primary tumour and one in a patient with head and neck cancer. The combination of IFN is possible with 5-FU and DDP. The recommended dose of IFN is 2 x 10(6) U/m2 s.c. in patients with no prior exposure to DDP or i.v. morphine, given together with 5-FU (750 mg/m2, days 1-5, CI) and DDP (75 mg/m2, day 1) on a 28-day cycle.

Adult↗