Phase I and II clinical trials have demonstrated acceptable toxicity and promising activity of Ed... more Phase I and II clinical trials have demonstrated acceptable toxicity and promising activity of Edatrexate (10-EDAM). The objective of this multicentre phase II study was to determine the efficacy and toxicity of this agent in patients with metastatic melanoma. Sixteen previously untreated patients with metastatic melanoma received 10-EDAM, 80 mg/m2/week intravenously. Patients were evaluated for response and toxicity. There were no objective responses. The median dose intensity of 10-EDAM actually delivered was 56.25 mg/m2/week (70% of projected). Mucositis of any degree was encountered in 93.8% of patients. Grade 3 or 4 mucositis, skin rash, nausea, abdominal pain, neutropenia, thrombocytopenia, anemia and hyperbilirubinemia each were encountered in 1-2 patients. There was 1 toxic death due to 10-EDAM. 10-EDAM is an inactive agent in metastatic melanoma.
We have carried out a phase II study of intravenous menogaril given every four weeks in a group o... more We have carried out a phase II study of intravenous menogaril given every four weeks in a group of patients with breast cancer who had received no prior chemotherapy for metastatic disease. Myelosuppression, nausea and vomiting and local reactions were seen frequently. Six partial responses (median duration 154 days) were seen in 24 eligible patients. We conclude menogaril is active in breast cancer and recommend that because it can be delivered in high doses orally, future trials in this disease should focus on intense oral schedule.
Triple-negative breast cancer (TNBC) has a poor prognosis compared to other subtypes and lacks co... more Triple-negative breast cancer (TNBC) has a poor prognosis compared to other subtypes and lacks common therapeutic targets, including HER 2 and the estrogen and progesterone receptors. The clinicopathological heterogeneity of the disease and limited treatment options make clinical management particularly challenging. Here we present the results of a survey of Canadian clinical oncologists regarding treatment of TNBC, and review recent and ongoing clinical research in this area. Our survey results show that the majority of respondents use a combination of anthracyclines-taxanes as adjuvant therapy for early TNBC. For the first-line treatment of metastatic TNBC, most clinicians recommend taxanes, while single agent capecitabine and platinum-based therapies are more common for subsequent lines of therapy. Despite the ongoing development of novel targeted therapies, chemotherapy remains the mainstay of treatment for TNBC.
This economic analysis aimed to determine, from the perspective of a Canadian provincial governme... more This economic analysis aimed to determine, from the perspective of a Canadian provincial government payer, the cost-effectiveness of docetaxel (Taxotere: Sanofi-Aventis, Laval, QC) in combination with doxorubicin and cyclophosphamide (TAC) compared with 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) following primary surgery for breast cancer in women with operable, axillary lymph node-positive breast cancer. A Markov model looking at two time phases-5-year treatment and long-term follow-up-was constructed. Clinical events included clinical response (based on disease-free survival and overall survival) and rates of febrile neutropenia, stomatitis, diarrhea, and infections. Health states were "no recurrence," "locoregional recurrence," "distant recurrence," and "death." Costs were based on published sources and are presented in 2006 Canadian dollars. Model inputs included chemotherapy drug acquisition costs, chemotherapy administration...
Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation, 2001
In establishing decision models in the treatment and prevention of breast cancer, it is important... more In establishing decision models in the treatment and prevention of breast cancer, it is important to evaluate patients' preferences for such interventions. The objectives of the present study were: (i) to characterize women's preferences for breast cancer treatments and BRCA1/BRCA2 testing, using the rating scale and standard gamble techniques; and (ii) to identify factors associated with these quality of life indices. Data were collected from women with breast cancer (n = 60), high-risk relatives of women with breast cancer (n = 58), and women in the general population (n = 51). Regardless of group membership, participants favoured treatment and prevention options that involved minimal physical invasiveness. Women with breast cancer rated lumpectomy and radiation treatment more highly than high-risk relatives and women in the general population. Preferences did not differ according to participants' intentions to undergo BRCA testing. Age was the only demographic variabl...
Cancer prevention & control : CPC = Prévention & contrôle en cancérologie : PCC, 1998
The value of routine follow-up programs for patients with early stage breast cancer remains an ar... more The value of routine follow-up programs for patients with early stage breast cancer remains an area of controversy. In recent years, the cost-effectiveness of routine investigations has been questioned, and 2 prospective randomized clinical trials have shown no survival advantage to more intensive diagnostic follow-up approaches. Under the auspices of the Ottawa Regional Cancer Centre, a national survey of the practice patterns of Canadian surgical, radiation and medical oncologists was undertaken to measure current Canadian standards of care and to determine average costs of 5-year follow-up for patients completing primary treatment for stage I and II breast cancer. Standardized questionnaires were sent out to 130 surgeons, 59 radiation oncologists and 89 medical oncologists. The overall response rate was 44%. Based on the frequency of follow-up visits and investigations recommended by respondents, an average cost per patient for a 5-year follow-up plan was derived for each subspec...
Twenty-five evaluable patients with gliomas were treated with a combination of cytosine arabinosi... more Twenty-five evaluable patients with gliomas were treated with a combination of cytosine arabinoside plus cisplatin administered intravenously (IV). Ten of the 25 patients (40%) responded, including three of 13 patients (23%) with prior cranial radiation, and seven of 12 patients (58%) without prior cranial radiation. In a second study, intramuscular (IM) and oral caffeine were added to IV cytosine arabinoside plus cisplatin. Caffeine-induced seizures prevented escalation of the dose of caffeine to a level that would have been anticipated to potentiate the cytotoxicity of the cytosine arabinoside plus cisplatin. Twelve of 25 treated patients (48%) responded. Most of the patients had not received prior cranial radiation. In a third study, IV cytosine arabinoside was administered in combination with intracarotid and IV cisplatin, plus BCNU and tenoposide (VM-26). This study is continuing to accrue patients. Myelosuppression has been pronounced, but has generally been rapidly reversible...
In an era of fiscal restraint, it is important to evaluate the resources required to diagnose and... more In an era of fiscal restraint, it is important to evaluate the resources required to diagnose and treat serious illnesses. As breast cancer is the major malignancy affecting Canadian women, Statistics Canada has analysed the resources required to manage this disease in Canada, and the associated costs. Here we report the cost of initial diagnosis and treatment of nonmetastatic breast cancer, including adjuvant therapies. Treatment algorithms for Stages I, II, and III of the disease were derived by age group (< 50 or > or = 50 years old), principally from Canadian cancer registry data, supplemented, where necessary, by the results of surveys of Canadian oncologists. Data were obtained on breast cancer incidence by age, diagnostic work-up, stage at diagnosis, initial treatment, follow-up practice, duration of hospitalization and direct care costs. The direct health care costs associated with 'standard' diagnostic and therapeutic approaches were calculated for a cohort of...
Recent results of the U.S. Oncology Adjuvant Trial 9735 demonstrated significant disease-free sur... more Recent results of the U.S. Oncology Adjuvant Trial 9735 demonstrated significant disease-free survival and overall survival benefits for docetaxel and cyclophosphamide (tc) compared with doxorubicin and cyclophosphamide (ac) in the adjuvant treatment of operable invasive breast cancer. Based on clinical data from the 9735 study, we evaluated the lifetime cost-effectiveness of tc compared with ac from the perspective of the Canadian publicly funded health care system. A Markov model was developed to estimate the incremental cost per quality-adjusted life-year gained and per life-year gained. Monthly survival and risk of disease recurrence up to 7 years were obtained directly from the overall survival and disease-free survival curves in the 9735 study; life-years beyond 7 years were estimated using the average life expectancy of age-matched women in the general Canadian population. Canadian-specific resource utilization and unit costs (in 2008 Canadian dollars) were applied to estimat...
OBJECTIVES: Two human papillomavirus (HPV) cervical cancer (CC) vaccines are currently available:... more OBJECTIVES: Two human papillomavirus (HPV) cervical cancer (CC) vaccines are currently available: a bivalent HPV-16/18 vaccine and a quadrivalent HPV-6/11/16/18 vaccine. The quadrivalent vaccine has an additional effect against genital warts, while the other offers broader protection against oncogenic non-vaccine types (cross-protection). The annual cost-consequences of both vaccines on HPV-related morbidity (i.e. abnormal pap smears, CIN1, CIN2/3 lesions, CC and genital warts) were evaluated within three European countries: Italy, UK and the Netherlands. METHODS: A static population model was developed in Excel®. The two vaccines differ in crossprotection level based on the latest results from clinical trials using, for both, the HPV naïve population (without current or past HPV infection) and country specific HPV-type distribution in each related lesion. Costing was performed from a health care perspective and obtained from published sources and official tariff data. No discounting was applied as results are reported over one year after reaching steady state. RESULTS: The more cross protection observed with the bivalent vaccine leads to an additional reduction in 9 510, 22 189, and 781 abnormal pap smears respectively in Italy, UK and the Netherlands; 275, 22,951, and 184 CIN1; 1,479, 8,693, and 833 CIN2/3; and 345, 142, and 28 CC cases while the quadrivalent vaccine results in 23,260, 50,324, and 2,983 genital wart cases prevented per year. More cost was saved with the bivalent compared with the quadrivalent vaccine and the amount per country per year was estimated at a2,719,040, £22,044,085, and a1,951,369 respectively. CONCLUSIONS: Within the Italian, the UK and the Netherlands settings the additional level of cross protection of the bivalent vaccine allows for more reduction in CC and HPV-related morbidity resulting in more cost savings that completely offset the benefit the quadrivalent vaccine has in preventing genital warts.
This report may be used, in whole or in part, as the basis for development of clinical practice g... more This report may be used, in whole or in part, as the basis for development of clinical practice guidelines and other quality enhancement tools, or a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied.
To optimize patient management in breast cancer a number of factors are considered, including hor... more To optimize patient management in breast cancer a number of factors are considered, including hormone receptor and HER2 status. A feasible approach for women with less aggressive, estrogen receptor/HER2-positive metastatic breast cancer is to consider trastuzumab (Herceptin; F. Hoffmann-La Roche, Basel, Switzerland) combined with endocrine therapy. Randomized clinical trials are ongoing to assess the combination of trastuzumab with aromatase inhibitors. In patients with aggressive HER2-positive metastatic breast cancer, trastuzumab/chemotherapy combination regimens are warranted. When administered first line in combination with a taxane, trastuzumab improves all clinical outcome parameters, including survival, in such patients. Trastuzumab adds little to the toxicity profile of taxanes, and trastuzumab combination therapy is associated with improvements in quality of life when compared with chemotherapy alone. There is encouraging evidence of improved efficacy when trastuzumab is co...
A practical guide to the management of menopausal symptoms in breast cancer patients Abstract Bre... more A practical guide to the management of menopausal symptoms in breast cancer patients Abstract Breast cancer is the most frequently diagnosed cancer in Canadian women. As a result of increased screening and improved treatment, more women are becoming long-term breast cancer survivors. However, due to either their treatment or prolonged survival, many of these women now have to face the consequences of premature menopause and prolonged estrogen deprivation. Hormone replacement therapy/estrogen replacement therapy (HRT/ERT) has, in the past, been recommended to healthy women at menopause not only for relief of short-term menopausal changes, particularly hot flashes, but also for its benefits on bone density,
ABSTRACT The social, psychological and demographic factors associated with the decision of high-r... more ABSTRACT The social, psychological and demographic factors associated with the decision of high-risk women to undergo breast cancer gene testing were investigated within the framework of the Health Belief Model (HBM). Participants were 108 Canadian volunteers from the following groups: (1) women who had at least one female blood relative diagnosed with breast cancer within the past two years (HR group; n = 58) and (2) women from the general population who had never been diagnosed with cancer of any type (GP group; n = 50). All participants completed a survey designed to collect demographic information, familial cancer history, disease perceptions/attitudes and interest in gene testing for breast cancer susceptibility. As expected, the attitudes of HR group women about gene testing differed from those in the general population on a number of variables. Specifically, women with an affected family member were more likely to be interested in genetic testing than those from the general population. Perceptions of increased personal risk for ovarian cancer were associated with interest in genetic testing for BRCA1/BRCA2 mutations among women with a family history of the disease. With respect to HBM variables, greater perceived psychological benefits and fewer perceived costs of BRCA1/BRCA2 testing were associated with interest in gene testing for women in both groups. Understanding the sociodemographic and individual predictors of interest in genetic testing will provide more realistic estimates regarding demand for breast cancer gene testing and will assist in the development of effective genetic counselling protocols for high-risk women.
Twenty patients with astrocytomas recurrent after surgery + radiation were treated on a phase II ... more Twenty patients with astrocytomas recurrent after surgery + radiation were treated on a phase II protocol of the new anthracycline derivative menogaril 115 mg/m 2 administered intravenously once per week. Sixteen patients were evaluable for treatment efficacy. No patient achieved a major therapeutic response. Three patients (19%) had stable disease for greater than 8 weeks, including one who showed minor evidence of tumor regression, but less than 50%. Thirteen patients failed. Treatment was well tolerated. One patient developed granulocytopenia, while none developed thrombocytopenia. Four patients required an interruption in their treatment for one to two weeks because of development of granulocytopenia (one patient) or other reasons. Other toxic effects included arm vein phlebitis and skin irritation, skin discoloration of the infused arm, mild to moderate nausea and vomiting, diarrhea, stomatitis, and a fatal central venous catheter infection. Despite the fact that menogaril appeared to have therapeutic activity against recurrent astrocytomas in our phase I studies, we could not document any activity in this phase II study.
Thirty-six patients were entered on this study to determine the pharmacology, bioavailability, an... more Thirty-six patients were entered on this study to determine the pharmacology, bioavailability, and toxicity of three different oral formulations of cyclophosphamide (Cytoxan | Endoxan | and an investigational direct compression tablet). Patients were randomized with respect to the order in which they received the different oral cyclophosphamide preparations, and received each one for two weeks followed by a two week washout period. Concurrent chemotherapy was allowed provided it remained constant across all 3 courses of cyclophosphamide. Plasma concentrations of cyclophosphamide and phosphoramide mustard were measured by gas chromatography with electron capture detection. Peak plasma cyclophosphamide concentrations and times to peak plasma cyclophosphamide and phosphoramide mustard preparations were significantly greater for Endoxan | than for Cytoxan | and the investigational direct compression tablet. Drug area under the concentration-time curve (AUC), bioavailability, and plasma elimination half-life could not be reliably calculated for Endoxan | but were similar for Cytoxan | and the investigational formulation. Based on AUC comparisons, bioavailability of parent compound (relative to an oral cyclophosphamide solution) was 85% for Cytoxan | and 69% for the investigational formulation. This difference was not significant. There were no significant differences between the 3 formulations with respect to any individual type of toxicity, although the investigational formulation tended to be associated with somewhat less overall toxicity (p = 0.08).
Phase I and II clinical trials have demonstrated acceptable toxicity and promising activity of Ed... more Phase I and II clinical trials have demonstrated acceptable toxicity and promising activity of Edatrexate (10-EDAM). The objective of this multicentre phase II study was to determine the efficacy and toxicity of this agent in patients with metastatic melanoma. Sixteen previously untreated patients with metastatic melanoma received 10-EDAM, 80 mg/m2/week intravenously. Patients were evaluated for response and toxicity. There were no objective responses. The median dose intensity of 10-EDAM actually delivered was 56.25 mg/m2/week (70% of projected). Mucositis of any degree was encountered in 93.8% of patients. Grade 3 or 4 mucositis, skin rash, nausea, abdominal pain, neutropenia, thrombocytopenia, anemia and hyperbilirubinemia each were encountered in 1-2 patients. There was 1 toxic death due to 10-EDAM. 10-EDAM is an inactive agent in metastatic melanoma.
We have carried out a phase II study of intravenous menogaril given every four weeks in a group o... more We have carried out a phase II study of intravenous menogaril given every four weeks in a group of patients with breast cancer who had received no prior chemotherapy for metastatic disease. Myelosuppression, nausea and vomiting and local reactions were seen frequently. Six partial responses (median duration 154 days) were seen in 24 eligible patients. We conclude menogaril is active in breast cancer and recommend that because it can be delivered in high doses orally, future trials in this disease should focus on intense oral schedule.
Triple-negative breast cancer (TNBC) has a poor prognosis compared to other subtypes and lacks co... more Triple-negative breast cancer (TNBC) has a poor prognosis compared to other subtypes and lacks common therapeutic targets, including HER 2 and the estrogen and progesterone receptors. The clinicopathological heterogeneity of the disease and limited treatment options make clinical management particularly challenging. Here we present the results of a survey of Canadian clinical oncologists regarding treatment of TNBC, and review recent and ongoing clinical research in this area. Our survey results show that the majority of respondents use a combination of anthracyclines-taxanes as adjuvant therapy for early TNBC. For the first-line treatment of metastatic TNBC, most clinicians recommend taxanes, while single agent capecitabine and platinum-based therapies are more common for subsequent lines of therapy. Despite the ongoing development of novel targeted therapies, chemotherapy remains the mainstay of treatment for TNBC.
This economic analysis aimed to determine, from the perspective of a Canadian provincial governme... more This economic analysis aimed to determine, from the perspective of a Canadian provincial government payer, the cost-effectiveness of docetaxel (Taxotere: Sanofi-Aventis, Laval, QC) in combination with doxorubicin and cyclophosphamide (TAC) compared with 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) following primary surgery for breast cancer in women with operable, axillary lymph node-positive breast cancer. A Markov model looking at two time phases-5-year treatment and long-term follow-up-was constructed. Clinical events included clinical response (based on disease-free survival and overall survival) and rates of febrile neutropenia, stomatitis, diarrhea, and infections. Health states were "no recurrence," "locoregional recurrence," "distant recurrence," and "death." Costs were based on published sources and are presented in 2006 Canadian dollars. Model inputs included chemotherapy drug acquisition costs, chemotherapy administration...
Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation, 2001
In establishing decision models in the treatment and prevention of breast cancer, it is important... more In establishing decision models in the treatment and prevention of breast cancer, it is important to evaluate patients' preferences for such interventions. The objectives of the present study were: (i) to characterize women's preferences for breast cancer treatments and BRCA1/BRCA2 testing, using the rating scale and standard gamble techniques; and (ii) to identify factors associated with these quality of life indices. Data were collected from women with breast cancer (n = 60), high-risk relatives of women with breast cancer (n = 58), and women in the general population (n = 51). Regardless of group membership, participants favoured treatment and prevention options that involved minimal physical invasiveness. Women with breast cancer rated lumpectomy and radiation treatment more highly than high-risk relatives and women in the general population. Preferences did not differ according to participants' intentions to undergo BRCA testing. Age was the only demographic variabl...
Cancer prevention & control : CPC = Prévention & contrôle en cancérologie : PCC, 1998
The value of routine follow-up programs for patients with early stage breast cancer remains an ar... more The value of routine follow-up programs for patients with early stage breast cancer remains an area of controversy. In recent years, the cost-effectiveness of routine investigations has been questioned, and 2 prospective randomized clinical trials have shown no survival advantage to more intensive diagnostic follow-up approaches. Under the auspices of the Ottawa Regional Cancer Centre, a national survey of the practice patterns of Canadian surgical, radiation and medical oncologists was undertaken to measure current Canadian standards of care and to determine average costs of 5-year follow-up for patients completing primary treatment for stage I and II breast cancer. Standardized questionnaires were sent out to 130 surgeons, 59 radiation oncologists and 89 medical oncologists. The overall response rate was 44%. Based on the frequency of follow-up visits and investigations recommended by respondents, an average cost per patient for a 5-year follow-up plan was derived for each subspec...
Twenty-five evaluable patients with gliomas were treated with a combination of cytosine arabinosi... more Twenty-five evaluable patients with gliomas were treated with a combination of cytosine arabinoside plus cisplatin administered intravenously (IV). Ten of the 25 patients (40%) responded, including three of 13 patients (23%) with prior cranial radiation, and seven of 12 patients (58%) without prior cranial radiation. In a second study, intramuscular (IM) and oral caffeine were added to IV cytosine arabinoside plus cisplatin. Caffeine-induced seizures prevented escalation of the dose of caffeine to a level that would have been anticipated to potentiate the cytotoxicity of the cytosine arabinoside plus cisplatin. Twelve of 25 treated patients (48%) responded. Most of the patients had not received prior cranial radiation. In a third study, IV cytosine arabinoside was administered in combination with intracarotid and IV cisplatin, plus BCNU and tenoposide (VM-26). This study is continuing to accrue patients. Myelosuppression has been pronounced, but has generally been rapidly reversible...
In an era of fiscal restraint, it is important to evaluate the resources required to diagnose and... more In an era of fiscal restraint, it is important to evaluate the resources required to diagnose and treat serious illnesses. As breast cancer is the major malignancy affecting Canadian women, Statistics Canada has analysed the resources required to manage this disease in Canada, and the associated costs. Here we report the cost of initial diagnosis and treatment of nonmetastatic breast cancer, including adjuvant therapies. Treatment algorithms for Stages I, II, and III of the disease were derived by age group (< 50 or > or = 50 years old), principally from Canadian cancer registry data, supplemented, where necessary, by the results of surveys of Canadian oncologists. Data were obtained on breast cancer incidence by age, diagnostic work-up, stage at diagnosis, initial treatment, follow-up practice, duration of hospitalization and direct care costs. The direct health care costs associated with 'standard' diagnostic and therapeutic approaches were calculated for a cohort of...
Recent results of the U.S. Oncology Adjuvant Trial 9735 demonstrated significant disease-free sur... more Recent results of the U.S. Oncology Adjuvant Trial 9735 demonstrated significant disease-free survival and overall survival benefits for docetaxel and cyclophosphamide (tc) compared with doxorubicin and cyclophosphamide (ac) in the adjuvant treatment of operable invasive breast cancer. Based on clinical data from the 9735 study, we evaluated the lifetime cost-effectiveness of tc compared with ac from the perspective of the Canadian publicly funded health care system. A Markov model was developed to estimate the incremental cost per quality-adjusted life-year gained and per life-year gained. Monthly survival and risk of disease recurrence up to 7 years were obtained directly from the overall survival and disease-free survival curves in the 9735 study; life-years beyond 7 years were estimated using the average life expectancy of age-matched women in the general Canadian population. Canadian-specific resource utilization and unit costs (in 2008 Canadian dollars) were applied to estimat...
OBJECTIVES: Two human papillomavirus (HPV) cervical cancer (CC) vaccines are currently available:... more OBJECTIVES: Two human papillomavirus (HPV) cervical cancer (CC) vaccines are currently available: a bivalent HPV-16/18 vaccine and a quadrivalent HPV-6/11/16/18 vaccine. The quadrivalent vaccine has an additional effect against genital warts, while the other offers broader protection against oncogenic non-vaccine types (cross-protection). The annual cost-consequences of both vaccines on HPV-related morbidity (i.e. abnormal pap smears, CIN1, CIN2/3 lesions, CC and genital warts) were evaluated within three European countries: Italy, UK and the Netherlands. METHODS: A static population model was developed in Excel®. The two vaccines differ in crossprotection level based on the latest results from clinical trials using, for both, the HPV naïve population (without current or past HPV infection) and country specific HPV-type distribution in each related lesion. Costing was performed from a health care perspective and obtained from published sources and official tariff data. No discounting was applied as results are reported over one year after reaching steady state. RESULTS: The more cross protection observed with the bivalent vaccine leads to an additional reduction in 9 510, 22 189, and 781 abnormal pap smears respectively in Italy, UK and the Netherlands; 275, 22,951, and 184 CIN1; 1,479, 8,693, and 833 CIN2/3; and 345, 142, and 28 CC cases while the quadrivalent vaccine results in 23,260, 50,324, and 2,983 genital wart cases prevented per year. More cost was saved with the bivalent compared with the quadrivalent vaccine and the amount per country per year was estimated at a2,719,040, £22,044,085, and a1,951,369 respectively. CONCLUSIONS: Within the Italian, the UK and the Netherlands settings the additional level of cross protection of the bivalent vaccine allows for more reduction in CC and HPV-related morbidity resulting in more cost savings that completely offset the benefit the quadrivalent vaccine has in preventing genital warts.
This report may be used, in whole or in part, as the basis for development of clinical practice g... more This report may be used, in whole or in part, as the basis for development of clinical practice guidelines and other quality enhancement tools, or a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied.
To optimize patient management in breast cancer a number of factors are considered, including hor... more To optimize patient management in breast cancer a number of factors are considered, including hormone receptor and HER2 status. A feasible approach for women with less aggressive, estrogen receptor/HER2-positive metastatic breast cancer is to consider trastuzumab (Herceptin; F. Hoffmann-La Roche, Basel, Switzerland) combined with endocrine therapy. Randomized clinical trials are ongoing to assess the combination of trastuzumab with aromatase inhibitors. In patients with aggressive HER2-positive metastatic breast cancer, trastuzumab/chemotherapy combination regimens are warranted. When administered first line in combination with a taxane, trastuzumab improves all clinical outcome parameters, including survival, in such patients. Trastuzumab adds little to the toxicity profile of taxanes, and trastuzumab combination therapy is associated with improvements in quality of life when compared with chemotherapy alone. There is encouraging evidence of improved efficacy when trastuzumab is co...
A practical guide to the management of menopausal symptoms in breast cancer patients Abstract Bre... more A practical guide to the management of menopausal symptoms in breast cancer patients Abstract Breast cancer is the most frequently diagnosed cancer in Canadian women. As a result of increased screening and improved treatment, more women are becoming long-term breast cancer survivors. However, due to either their treatment or prolonged survival, many of these women now have to face the consequences of premature menopause and prolonged estrogen deprivation. Hormone replacement therapy/estrogen replacement therapy (HRT/ERT) has, in the past, been recommended to healthy women at menopause not only for relief of short-term menopausal changes, particularly hot flashes, but also for its benefits on bone density,
ABSTRACT The social, psychological and demographic factors associated with the decision of high-r... more ABSTRACT The social, psychological and demographic factors associated with the decision of high-risk women to undergo breast cancer gene testing were investigated within the framework of the Health Belief Model (HBM). Participants were 108 Canadian volunteers from the following groups: (1) women who had at least one female blood relative diagnosed with breast cancer within the past two years (HR group; n = 58) and (2) women from the general population who had never been diagnosed with cancer of any type (GP group; n = 50). All participants completed a survey designed to collect demographic information, familial cancer history, disease perceptions/attitudes and interest in gene testing for breast cancer susceptibility. As expected, the attitudes of HR group women about gene testing differed from those in the general population on a number of variables. Specifically, women with an affected family member were more likely to be interested in genetic testing than those from the general population. Perceptions of increased personal risk for ovarian cancer were associated with interest in genetic testing for BRCA1/BRCA2 mutations among women with a family history of the disease. With respect to HBM variables, greater perceived psychological benefits and fewer perceived costs of BRCA1/BRCA2 testing were associated with interest in gene testing for women in both groups. Understanding the sociodemographic and individual predictors of interest in genetic testing will provide more realistic estimates regarding demand for breast cancer gene testing and will assist in the development of effective genetic counselling protocols for high-risk women.
Twenty patients with astrocytomas recurrent after surgery + radiation were treated on a phase II ... more Twenty patients with astrocytomas recurrent after surgery + radiation were treated on a phase II protocol of the new anthracycline derivative menogaril 115 mg/m 2 administered intravenously once per week. Sixteen patients were evaluable for treatment efficacy. No patient achieved a major therapeutic response. Three patients (19%) had stable disease for greater than 8 weeks, including one who showed minor evidence of tumor regression, but less than 50%. Thirteen patients failed. Treatment was well tolerated. One patient developed granulocytopenia, while none developed thrombocytopenia. Four patients required an interruption in their treatment for one to two weeks because of development of granulocytopenia (one patient) or other reasons. Other toxic effects included arm vein phlebitis and skin irritation, skin discoloration of the infused arm, mild to moderate nausea and vomiting, diarrhea, stomatitis, and a fatal central venous catheter infection. Despite the fact that menogaril appeared to have therapeutic activity against recurrent astrocytomas in our phase I studies, we could not document any activity in this phase II study.
Thirty-six patients were entered on this study to determine the pharmacology, bioavailability, an... more Thirty-six patients were entered on this study to determine the pharmacology, bioavailability, and toxicity of three different oral formulations of cyclophosphamide (Cytoxan | Endoxan | and an investigational direct compression tablet). Patients were randomized with respect to the order in which they received the different oral cyclophosphamide preparations, and received each one for two weeks followed by a two week washout period. Concurrent chemotherapy was allowed provided it remained constant across all 3 courses of cyclophosphamide. Plasma concentrations of cyclophosphamide and phosphoramide mustard were measured by gas chromatography with electron capture detection. Peak plasma cyclophosphamide concentrations and times to peak plasma cyclophosphamide and phosphoramide mustard preparations were significantly greater for Endoxan | than for Cytoxan | and the investigational direct compression tablet. Drug area under the concentration-time curve (AUC), bioavailability, and plasma elimination half-life could not be reliably calculated for Endoxan | but were similar for Cytoxan | and the investigational formulation. Based on AUC comparisons, bioavailability of parent compound (relative to an oral cyclophosphamide solution) was 85% for Cytoxan | and 69% for the investigational formulation. This difference was not significant. There were no significant differences between the 3 formulations with respect to any individual type of toxicity, although the investigational formulation tended to be associated with somewhat less overall toxicity (p = 0.08).
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Papers by Shail Verma