Bernard Candas - Academia.edu (original) (raw)

Papers by Bernard Candas

Research paper thumbnail of 647: Relationship Between the PSA Value at First Visit and PSA Progression and Prostate Cancer Diagnosis at Annual Follow-Up Visits

The Journal of Urology, 2004

Research paper thumbnail of Engaging patient representatives in the identification and prioritization of Health Technology Assessment topics

Effective ways to incorporate the patient perspective in Health Technology Assessment (HTA) are n... more Effective ways to incorporate the patient perspective in Health Technology Assessment (HTA) are needed. Embedded within a wider project that aimed to develop and evaluate interventions to engage patient representatives alongside with clinicians and managers in the conduct of a HTA, we sought to describe this process and its results on the identification and prioritization of HTA topics. Three steps of the HTA process were involved: 1) suggestion of HTA topics, 2) filtration and refinement of topics, and 3) prioritization of topics. Patient representatives, clinicians and managers from eastern and central regions of Quebec (Canada) were asked to suggest potential HTA topics in the field of cancer. In total, representatives of all stakeholder groups suggested 30 topics. A filtration and refinement process allowed formulating 12 HTA questions from these topics. Participants were then asked to attend a consensus meeting for prioritizing HTA topics. The top three priorities emerging from the prioritization meeting were: "group meetings with an interdisciplinary team in oncology (including community group representatives) in support for new cancer patients", "strategies to invite people to participate in cancer screening programs" and "teleconsultation for preliminary evaluation and follow-up of cancer patients in rural and remote areas". These priorities differed from those identified in the pre-meeting survey. Patient representatives, clinicians and managers had different perspectives on topics to prioritize but could find a consensus. Engaging patient representatives in different activities related to the identification and prioritization of topics appear to influence the final selection of HTA topics.

Research paper thumbnail of Printed in U.S.A. Copyright © 1998 by The Endocrine Society Comparison of the Effects of the New Orally Active Antiestrogen EM-800 with ICI 182 780 and Toremifene on Estrogen-Sensitive Parameters in the Ovariectomized Mouse

The nonsteroidal antiestrogen EM-800 is approximately 10-fold more potent than ICI 182 780, the m... more The nonsteroidal antiestrogen EM-800 is approximately 10-fold more potent than ICI 182 780, the most potent known steroidal antiestrogen, at inhibiting estrone-stimulated uterine weight in ovariectomized mice (half-maximal inhibitory daily sc doses of 0.2 and 2.0 �g, respectively). At maximal doses, however, both compounds lead to a similar maximal 90 % inhibition of estrone-stimulated uterine weight. A 10-fold higher activity of EM-800 compared with ICI 182 780 was also observed on estrone-stimulated vaginal weight, with maximal inhibitions of 96 % and 90%, respectively, achieved by the two compounds. In addition, EM-800 injected sc or administered orally led to a marked loss of uterine and vaginal estrogen receptor levels measured by binding assay, whereas ICI 182 780 exerted no ESTROGENS are recognized to play the predominant role in breast cancer development and growth (1). As the

Research paper thumbnail of An Adaptive Controller Of Glycemia Based On A Physiological Model Of The Insulin-dependent Glucose Removal

Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society Volume 13: 1991

Research paper thumbnail of Does socio-economic status influence the effect of multimorbidity on the frequent use of ambulatory care services in a universal healthcare system? A population-based cohort study

BMC Health Services Research

BackgroundFrequent healthcare users place a significant burden on health systems. Factors such as... more BackgroundFrequent healthcare users place a significant burden on health systems. Factors such as multimorbidity and low socioeconomic status have been associated with high use of ambulatory care services (emergency rooms, general practitioners and specialist physicians). However, the combined effect of these two factors remains poorly understood. Our goal was to determine whether the risk of being a frequent user of ambulatory care is influenced by an interaction between multimorbidity and socioeconomic status, in an entire population covered by a universal health system.MethodsUsing a linkage of administrative databases, we conducted a population-based cohort study of all adults in Quebec, Canada. Multimorbidity (defined as the number of different diseases) was assessed over a two-year period from April 1st 2012 to March 31st 2014 and socioeconomic status was estimated using a validated material deprivation index. Frequents users for a particular category of ambulatory services ha...

Research paper thumbnail of Combined impacts of multimorbidity and mental disorders on frequent emergency department visits: a retrospective cohort study in Quebec, Canada

Canadian Medical Association Journal

Research paper thumbnail of Validation of the Combined Comorbidity Index of Charlson and Elixhauser to Predict 30-Day Mortality Across ICD-9 and ICD-10

Medical care, 2018

To validate and compare performance of an International Classification of Diseases, tenth revisio... more To validate and compare performance of an International Classification of Diseases, tenth revision (ICD-10) version of a combined comorbidity index merging conditions of Charlson and Elixhauser measures against individual measures in the prediction of 30-day mortality. To select a weight derivation method providing optimal performance across ICD-9 and ICD-10 coding systems. Using 2 adult population-based cohorts of patients with hospital admissions in ICD-9 (2005, n=337,367) and ICD-10 (2011, n=348,820), we validated a combined comorbidity index by predicting 30-day mortality with logistic regression. To appreciate performance of the Combined index and both individual measures, factors impacting indices performance such as population characteristics and weight derivation methods were accounted for. We applied 3 scoring methods (Van Walraven, Schneeweiss, and Charlson) and determined which provides best predictive values. Combined index [c-statistics: 0.853 (95% confidence interval: ...

Research paper thumbnail of Response to Precision on the Scope on the Combined Comorbidity Index Published in: Validation of the Combined Comorbidity Index of Charlson and Elixhauser to Predict 30-Day Mortality Across ICD-9 and ICD-10

Medical care, 2018

To the Editor: We read with interest the study by Simard and colleagues, which validated an Inter... more To the Editor: We read with interest the study by Simard and colleagues, which validated an International Classification of Diseases, Tenth Revision (ICD-10) version of the combined comorbidity score to predict 30-day mortality using administrative health care data from Quebec, Canada.1 The combined comorbidity score was previously developed to predict mortality in US Medicare patients by combining conditions contained in the Charlson et al2 and Elixhauser et al3 comorbidity indices.4 We would like to call the authors’ and readers’ attention to another study that we published in Medical Care at the end of last year, which evaluated and compared different ICD-10 Clinical Modification (ICD10-CM) versions of the combined comorbidity score to predict 30-day hospital readmission using administrative claims data in the US.5 Although not the first published ICD-10 validation study on the combined comorbidity score, the validation by Simard and colleagues is important because it focuses on mortality, which we were not able to examine in the previous US study, and it extends the validation to other populations, time periods, and ICD-10 coding systems (ie, ICD-10-CA, the Canada modification vs. ICD-10-CM, the US modification). Simard and colleagues’ study also suggests that the relative performance of the combined comorbidity score versus the component Charlson and Elixhauser scores is insensitive to the choice of 3 weighting strategies, which is an important finding. We further commend Simard and colleagues for providing the specific codes used in the version of the ICD-10-CA scores that they validated, as we did for ICD-10-CM. However, we would like to point out that ICD-9 and ICD-10 coding systems can vary across countries, as different countries implement modifications to reflect their specific settings. We urge other researchers to continue to validate and improve comorbidity scores across populations, outcomes, and countries with different ICD-10 implementations.

Research paper thumbnail of The Development of Antiretroviral Therapy Order Set for Admitted Adult HIV-Infected Patients

International Journal of Medicine and Pharmacy

Research paper thumbnail of Understanding cancer networks better to implement them more effectively: a mixed methods multi-case study

Implementation Science, 2015

Research paper thumbnail of Barriers and facilitators to implementing continuous quality improvement programs in colonoscopy services: a mixed methods systematic review

Endoscopy International Open, 2015

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibi... more This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. #1 Search Colonoscopy[mh] OR Colonoscop*[tiab] OR Sigmoidoscop*[tiab] OR Proctosigmoidoscop*[tiab] Candas Bernard et al. Continuous quality improvement programs in colonoscopy services … Endoscopy International Open 2016; 04: E118-E133 Review E119 THIEME This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. 4 649 Duplicates 10843 titles retrieved from databases MEDLINE, Ovid, Cochrane Central Register for Contolled Trials,

Research paper thumbnail of Appariement des données administratives pour l’estimation de l’utilisation des ressources médicales

Revue d'Épidémiologie et de Santé Publique, 2012

Research paper thumbnail of Développement de la surveillance de l'ostéoporose au Québec: Utilisation des bases de données médico-administratives

Research paper thumbnail of Down-staging of early stage prostate cancer before radical prostatectomy: The first randomized trial of neoadjuvant combination therapy with flutamide and a luteinizing hormone-releasing hormone agonist

Research paper thumbnail of Comparison of in vitro effects of the pure antiandrogens OH-flutamide, casodex, and nilutamide on androgen-sensitive parameters

Research paper thumbnail of Interpreting the Quebec prostate cancer study

CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne, Jan 20, 2002

Research paper thumbnail of Long-Term Combined Androgen Blockade Alone for Localized Prostate Cancer

Molecular urology, 1999

The effect of long-term continuous combined androgen blockade (CAB) administered alone has been s... more The effect of long-term continuous combined androgen blockade (CAB) administered alone has been studied in 26 patients with stage B(2)/T(2) and 115 with stage C/T(3) prostate cancer who did not accept or were not candidates for other forms of therapy. In the 26 patients with stage T(2) disease who have received continuous CAB with an LHRH agonist and flutamide, progression of cancer, as evidenced by rising serum prostate specific antigen (PSA), was observed in only one patient receiving CAB, occurring after 7.3 years of continuous CAB treatment. Treatment with CAB was then stopped in 20 patients with stage T(2) cancer after a median period of 7.2 years. Failure or PSA rise occurred in 2 of these patients after a median follow-up of 3.1 years following cessation of CAB, and one died from prostate cancer. The benefits observed with CAB alone in localized disease compare favorably with those obtained by radical prostatectomy or radiotherapy alone. Twenty-six patients with stage T(3) ca...

Research paper thumbnail of Effects of the antiestrogen EM-800 (SCH 57050) and cyclophosphamide alone and in combination on growth of human ZR-75-1 breast cancer xenografts in nude mice

Cancer research, Jan 15, 1999

Human breast cancer proliferates as heterogeneous cell populations that exhibit different sensiti... more Human breast cancer proliferates as heterogeneous cell populations that exhibit different sensitivities to therapeutic agents. A logical approach to control these different cancer cell populations is the use of combined treatment with agents that block cell proliferation or induce apoptosis via different mechanisms. We therefore investigated the effect of treatment with the novel pure antiestrogen EM-800, alone or in combination with chemotherapy, on the growth of ZR-75-1 human breast tumors in nude mice, a well-recognized model of human breast cancer. Mice bearing estrone-releasing silastic implants as estrogenic stimulus received EM-800 or cyclophosphamide alone or in combination for 227 days. Cyclophosphamide (256 mg/kg/2 weeks) was administered by i.p. injection in 64 mg/kg fractions over 4 consecutive days with repetition of the cycle every 14 days. EM-800 was administered p.o. once daily at the maximally effective dose of 300 microg/mouse. After 227 days of treatment, average ...

Research paper thumbnail of Effect of combined treatment with the pure antiestrogen EM-800 and radiotherapy on the growth of human ZR-75-1 breast cancer xenografts in nude mice

Cancer research, 1999

Human breast tumors are usually composed of heterogeneous cell populations that exhibit different... more Human breast tumors are usually composed of heterogeneous cell populations that exhibit different sensitivities to therapeutic agents. We therefore investigated the effect of treatment with various regimens of the novel pure antiestrogen EM-800, alone or in combination with external beam radiation therapy, on the growth of human ZR-75-1 xenografts in athymic mice. The animals received a maximal dose of EM-800 (300 microg, p.o.) and/or radiotherapy at the dose of 10 Gy. 2.5 Gy fractions were administered over a 9-day period in four sessions of 13.7 min each (250-kilovolt Siemens with 2-mm aluminum filtration at 90 cm from the source origin). EM-800 was administered p.o. once daily, whereas radiotherapy was repeated every 35 days. Tumor size was expressed as a percentage of the initial tumor size, which was assigned a value of 100%. Average tumor size increased by 514% in ovariectomized mice supplemented with estrone alone for 259 days compared with the pretreatment value. Treatment w...

Research paper thumbnail of Comparison of the effects of the antiestrogens EM-800 and tamoxifen on the growth of human breast ZR-75-1 cancer xenografts in nude mice

Cancer research, 1998

Although estrone supplementation in ovariectomized (OVX) nude mice bearing ZR-75-1 xenografts cau... more Although estrone supplementation in ovariectomized (OVX) nude mice bearing ZR-75-1 xenografts caused a 365% increase in average tumor size during the 4-month treatment period, administration of the antiestrogen EM-800 at the daily oral doses of 50, 150, or 400 microg completely prevented estrogen-stimulated tumor growth. At the same doses of tamoxifen, tumor size was inhibited to 189, 117, and 120% above pretreatment values. However, when EM-800 (150 microg/day) was added to the daily 150- and 400-microg doses of tamoxifen, final tumor size was decreased further to 12 and 38% above pretreatment values, respectively. EM-800 (400 microg daily) administered to estrone-supplemented OVX mice caused complete, partial, and stable responses in 11, 22, and 49% of estrone-stimulated tumors, respectively, whereas 19% (7 of 37) progressed. At the same dose of tamoxifen, the corresponding responses were 3% (complete response), 3% (partial response), and 25% (no change), whereas 69% (22 of 32) of...

Research paper thumbnail of 647: Relationship Between the PSA Value at First Visit and PSA Progression and Prostate Cancer Diagnosis at Annual Follow-Up Visits

The Journal of Urology, 2004

Research paper thumbnail of Engaging patient representatives in the identification and prioritization of Health Technology Assessment topics

Effective ways to incorporate the patient perspective in Health Technology Assessment (HTA) are n... more Effective ways to incorporate the patient perspective in Health Technology Assessment (HTA) are needed. Embedded within a wider project that aimed to develop and evaluate interventions to engage patient representatives alongside with clinicians and managers in the conduct of a HTA, we sought to describe this process and its results on the identification and prioritization of HTA topics. Three steps of the HTA process were involved: 1) suggestion of HTA topics, 2) filtration and refinement of topics, and 3) prioritization of topics. Patient representatives, clinicians and managers from eastern and central regions of Quebec (Canada) were asked to suggest potential HTA topics in the field of cancer. In total, representatives of all stakeholder groups suggested 30 topics. A filtration and refinement process allowed formulating 12 HTA questions from these topics. Participants were then asked to attend a consensus meeting for prioritizing HTA topics. The top three priorities emerging from the prioritization meeting were: "group meetings with an interdisciplinary team in oncology (including community group representatives) in support for new cancer patients", "strategies to invite people to participate in cancer screening programs" and "teleconsultation for preliminary evaluation and follow-up of cancer patients in rural and remote areas". These priorities differed from those identified in the pre-meeting survey. Patient representatives, clinicians and managers had different perspectives on topics to prioritize but could find a consensus. Engaging patient representatives in different activities related to the identification and prioritization of topics appear to influence the final selection of HTA topics.

Research paper thumbnail of Printed in U.S.A. Copyright © 1998 by The Endocrine Society Comparison of the Effects of the New Orally Active Antiestrogen EM-800 with ICI 182 780 and Toremifene on Estrogen-Sensitive Parameters in the Ovariectomized Mouse

The nonsteroidal antiestrogen EM-800 is approximately 10-fold more potent than ICI 182 780, the m... more The nonsteroidal antiestrogen EM-800 is approximately 10-fold more potent than ICI 182 780, the most potent known steroidal antiestrogen, at inhibiting estrone-stimulated uterine weight in ovariectomized mice (half-maximal inhibitory daily sc doses of 0.2 and 2.0 �g, respectively). At maximal doses, however, both compounds lead to a similar maximal 90 % inhibition of estrone-stimulated uterine weight. A 10-fold higher activity of EM-800 compared with ICI 182 780 was also observed on estrone-stimulated vaginal weight, with maximal inhibitions of 96 % and 90%, respectively, achieved by the two compounds. In addition, EM-800 injected sc or administered orally led to a marked loss of uterine and vaginal estrogen receptor levels measured by binding assay, whereas ICI 182 780 exerted no ESTROGENS are recognized to play the predominant role in breast cancer development and growth (1). As the

Research paper thumbnail of An Adaptive Controller Of Glycemia Based On A Physiological Model Of The Insulin-dependent Glucose Removal

Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society Volume 13: 1991

Research paper thumbnail of Does socio-economic status influence the effect of multimorbidity on the frequent use of ambulatory care services in a universal healthcare system? A population-based cohort study

BMC Health Services Research

BackgroundFrequent healthcare users place a significant burden on health systems. Factors such as... more BackgroundFrequent healthcare users place a significant burden on health systems. Factors such as multimorbidity and low socioeconomic status have been associated with high use of ambulatory care services (emergency rooms, general practitioners and specialist physicians). However, the combined effect of these two factors remains poorly understood. Our goal was to determine whether the risk of being a frequent user of ambulatory care is influenced by an interaction between multimorbidity and socioeconomic status, in an entire population covered by a universal health system.MethodsUsing a linkage of administrative databases, we conducted a population-based cohort study of all adults in Quebec, Canada. Multimorbidity (defined as the number of different diseases) was assessed over a two-year period from April 1st 2012 to March 31st 2014 and socioeconomic status was estimated using a validated material deprivation index. Frequents users for a particular category of ambulatory services ha...

Research paper thumbnail of Combined impacts of multimorbidity and mental disorders on frequent emergency department visits: a retrospective cohort study in Quebec, Canada

Canadian Medical Association Journal

Research paper thumbnail of Validation of the Combined Comorbidity Index of Charlson and Elixhauser to Predict 30-Day Mortality Across ICD-9 and ICD-10

Medical care, 2018

To validate and compare performance of an International Classification of Diseases, tenth revisio... more To validate and compare performance of an International Classification of Diseases, tenth revision (ICD-10) version of a combined comorbidity index merging conditions of Charlson and Elixhauser measures against individual measures in the prediction of 30-day mortality. To select a weight derivation method providing optimal performance across ICD-9 and ICD-10 coding systems. Using 2 adult population-based cohorts of patients with hospital admissions in ICD-9 (2005, n=337,367) and ICD-10 (2011, n=348,820), we validated a combined comorbidity index by predicting 30-day mortality with logistic regression. To appreciate performance of the Combined index and both individual measures, factors impacting indices performance such as population characteristics and weight derivation methods were accounted for. We applied 3 scoring methods (Van Walraven, Schneeweiss, and Charlson) and determined which provides best predictive values. Combined index [c-statistics: 0.853 (95% confidence interval: ...

Research paper thumbnail of Response to Precision on the Scope on the Combined Comorbidity Index Published in: Validation of the Combined Comorbidity Index of Charlson and Elixhauser to Predict 30-Day Mortality Across ICD-9 and ICD-10

Medical care, 2018

To the Editor: We read with interest the study by Simard and colleagues, which validated an Inter... more To the Editor: We read with interest the study by Simard and colleagues, which validated an International Classification of Diseases, Tenth Revision (ICD-10) version of the combined comorbidity score to predict 30-day mortality using administrative health care data from Quebec, Canada.1 The combined comorbidity score was previously developed to predict mortality in US Medicare patients by combining conditions contained in the Charlson et al2 and Elixhauser et al3 comorbidity indices.4 We would like to call the authors’ and readers’ attention to another study that we published in Medical Care at the end of last year, which evaluated and compared different ICD-10 Clinical Modification (ICD10-CM) versions of the combined comorbidity score to predict 30-day hospital readmission using administrative claims data in the US.5 Although not the first published ICD-10 validation study on the combined comorbidity score, the validation by Simard and colleagues is important because it focuses on mortality, which we were not able to examine in the previous US study, and it extends the validation to other populations, time periods, and ICD-10 coding systems (ie, ICD-10-CA, the Canada modification vs. ICD-10-CM, the US modification). Simard and colleagues’ study also suggests that the relative performance of the combined comorbidity score versus the component Charlson and Elixhauser scores is insensitive to the choice of 3 weighting strategies, which is an important finding. We further commend Simard and colleagues for providing the specific codes used in the version of the ICD-10-CA scores that they validated, as we did for ICD-10-CM. However, we would like to point out that ICD-9 and ICD-10 coding systems can vary across countries, as different countries implement modifications to reflect their specific settings. We urge other researchers to continue to validate and improve comorbidity scores across populations, outcomes, and countries with different ICD-10 implementations.

Research paper thumbnail of The Development of Antiretroviral Therapy Order Set for Admitted Adult HIV-Infected Patients

International Journal of Medicine and Pharmacy

Research paper thumbnail of Understanding cancer networks better to implement them more effectively: a mixed methods multi-case study

Implementation Science, 2015

Research paper thumbnail of Barriers and facilitators to implementing continuous quality improvement programs in colonoscopy services: a mixed methods systematic review

Endoscopy International Open, 2015

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibi... more This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. #1 Search Colonoscopy[mh] OR Colonoscop*[tiab] OR Sigmoidoscop*[tiab] OR Proctosigmoidoscop*[tiab] Candas Bernard et al. Continuous quality improvement programs in colonoscopy services … Endoscopy International Open 2016; 04: E118-E133 Review E119 THIEME This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. 4 649 Duplicates 10843 titles retrieved from databases MEDLINE, Ovid, Cochrane Central Register for Contolled Trials,

Research paper thumbnail of Appariement des données administratives pour l’estimation de l’utilisation des ressources médicales

Revue d'Épidémiologie et de Santé Publique, 2012

Research paper thumbnail of Développement de la surveillance de l'ostéoporose au Québec: Utilisation des bases de données médico-administratives

Research paper thumbnail of Down-staging of early stage prostate cancer before radical prostatectomy: The first randomized trial of neoadjuvant combination therapy with flutamide and a luteinizing hormone-releasing hormone agonist

Research paper thumbnail of Comparison of in vitro effects of the pure antiandrogens OH-flutamide, casodex, and nilutamide on androgen-sensitive parameters

Research paper thumbnail of Interpreting the Quebec prostate cancer study

CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne, Jan 20, 2002

Research paper thumbnail of Long-Term Combined Androgen Blockade Alone for Localized Prostate Cancer

Molecular urology, 1999

The effect of long-term continuous combined androgen blockade (CAB) administered alone has been s... more The effect of long-term continuous combined androgen blockade (CAB) administered alone has been studied in 26 patients with stage B(2)/T(2) and 115 with stage C/T(3) prostate cancer who did not accept or were not candidates for other forms of therapy. In the 26 patients with stage T(2) disease who have received continuous CAB with an LHRH agonist and flutamide, progression of cancer, as evidenced by rising serum prostate specific antigen (PSA), was observed in only one patient receiving CAB, occurring after 7.3 years of continuous CAB treatment. Treatment with CAB was then stopped in 20 patients with stage T(2) cancer after a median period of 7.2 years. Failure or PSA rise occurred in 2 of these patients after a median follow-up of 3.1 years following cessation of CAB, and one died from prostate cancer. The benefits observed with CAB alone in localized disease compare favorably with those obtained by radical prostatectomy or radiotherapy alone. Twenty-six patients with stage T(3) ca...

Research paper thumbnail of Effects of the antiestrogen EM-800 (SCH 57050) and cyclophosphamide alone and in combination on growth of human ZR-75-1 breast cancer xenografts in nude mice

Cancer research, Jan 15, 1999

Human breast cancer proliferates as heterogeneous cell populations that exhibit different sensiti... more Human breast cancer proliferates as heterogeneous cell populations that exhibit different sensitivities to therapeutic agents. A logical approach to control these different cancer cell populations is the use of combined treatment with agents that block cell proliferation or induce apoptosis via different mechanisms. We therefore investigated the effect of treatment with the novel pure antiestrogen EM-800, alone or in combination with chemotherapy, on the growth of ZR-75-1 human breast tumors in nude mice, a well-recognized model of human breast cancer. Mice bearing estrone-releasing silastic implants as estrogenic stimulus received EM-800 or cyclophosphamide alone or in combination for 227 days. Cyclophosphamide (256 mg/kg/2 weeks) was administered by i.p. injection in 64 mg/kg fractions over 4 consecutive days with repetition of the cycle every 14 days. EM-800 was administered p.o. once daily at the maximally effective dose of 300 microg/mouse. After 227 days of treatment, average ...

Research paper thumbnail of Effect of combined treatment with the pure antiestrogen EM-800 and radiotherapy on the growth of human ZR-75-1 breast cancer xenografts in nude mice

Cancer research, 1999

Human breast tumors are usually composed of heterogeneous cell populations that exhibit different... more Human breast tumors are usually composed of heterogeneous cell populations that exhibit different sensitivities to therapeutic agents. We therefore investigated the effect of treatment with various regimens of the novel pure antiestrogen EM-800, alone or in combination with external beam radiation therapy, on the growth of human ZR-75-1 xenografts in athymic mice. The animals received a maximal dose of EM-800 (300 microg, p.o.) and/or radiotherapy at the dose of 10 Gy. 2.5 Gy fractions were administered over a 9-day period in four sessions of 13.7 min each (250-kilovolt Siemens with 2-mm aluminum filtration at 90 cm from the source origin). EM-800 was administered p.o. once daily, whereas radiotherapy was repeated every 35 days. Tumor size was expressed as a percentage of the initial tumor size, which was assigned a value of 100%. Average tumor size increased by 514% in ovariectomized mice supplemented with estrone alone for 259 days compared with the pretreatment value. Treatment w...

Research paper thumbnail of Comparison of the effects of the antiestrogens EM-800 and tamoxifen on the growth of human breast ZR-75-1 cancer xenografts in nude mice

Cancer research, 1998

Although estrone supplementation in ovariectomized (OVX) nude mice bearing ZR-75-1 xenografts cau... more Although estrone supplementation in ovariectomized (OVX) nude mice bearing ZR-75-1 xenografts caused a 365% increase in average tumor size during the 4-month treatment period, administration of the antiestrogen EM-800 at the daily oral doses of 50, 150, or 400 microg completely prevented estrogen-stimulated tumor growth. At the same doses of tamoxifen, tumor size was inhibited to 189, 117, and 120% above pretreatment values. However, when EM-800 (150 microg/day) was added to the daily 150- and 400-microg doses of tamoxifen, final tumor size was decreased further to 12 and 38% above pretreatment values, respectively. EM-800 (400 microg daily) administered to estrone-supplemented OVX mice caused complete, partial, and stable responses in 11, 22, and 49% of estrone-stimulated tumors, respectively, whereas 19% (7 of 37) progressed. At the same dose of tamoxifen, the corresponding responses were 3% (complete response), 3% (partial response), and 25% (no change), whereas 69% (22 of 32) of...