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Mackey J.R.,Cross Cancer Institute | Martin M.,Complutense University of Madrid | Pienkowski T.,European Health Center | Rolski J.,Podkarpackie Centrum Onkologii | And 26 more authors.
The Lancet Oncology | Year: 2013

Background: We compared standard adjuvant anthracycline chemotherapy with anthracycline-taxane combination chemotherapy in women with operable node-positive breast cancer. Here we report the final, 10-year follow-up analysis of disease-free survival, overall survival, and long-term safety. Methods: BCIRG 001 was an open label, phase 3, multicentre trial in which 1491 patients aged 18-70 years with node-positive, early breast cancer and a Karnofsky score of 80% or more were randomly assigned to adjuvant treatment with docetaxel, doxorubicin, and cyclophosphamide (TAC) or fluorouracil, doxorubicin, and cyclophosphamide (FAC) every 3 weeks for six cycles. Randomisation was stratified according to institution and number of involved axillary lymph nodes per patient (one to three vs four or more). Disease-free survival was the primary endpoint and was defined as the interval between randomisation and breast cancer relapse, second primary cancer, or death, whichever occurred first. Efficacy analyses were based on the intention-to-treat principle. BCIRG 001 is registered with ClinicalTrials.gov, number NCT00688740. Findings: Enrolement took place between June 11, 1997 and June 3, 1999; 745 patients were assigned to receive TAC and 746 patients were assigned to receive FAC. After a median follow-up of 124 months (IQR 90-126), disease-free survival was 62% (95% CI 58-65) for patients in the TAC group and 55% (51-59) for patients in the FAC group (hazard ratio [HR] 0·80, 95% CI 0·68-0·93; log-rank p=0·0043). 10-year overall survival was 76% (95% CI 72-79) for patients in the TAC group and 69% (65-72) for patients in the FAC group (HR 0·74, 0·61-0·90; log-rank p=0·0020). TAC improved disease-free survival relative to FAC irrespective of nodal, hormone receptor, and HER2 status, although not all differences were significant in these subgroup analyses. Grade 3-4 heart failure occurred in 26 (3%) patients in the TAC group and 17 (2%) patients in the FAC group, and caused death in two patients in the TAC group and four patients in the FAC group. A substantial decrease in left ventricular ejection fraction (defined as a relative decrease from baseline of 20% or more) was seen in 58 (17%) patients who received TAC and 41 (15%) patients who received FAC. Six patients who received TAC developed leukaemia or myelodysplasia, as did three patients who received FAC. Interpretation: Our results provide evidence that the initial therapeutic outcomes seen at the 5-year follow-up with a docetaxel-containing adjuvant regimen are maintained at 10 years. However, a substantial percentage of patients had a decrease in left ventricular ejection fraction, probably caused by anthracycline therapy, which warrants further investigation. Funding: Sanofi. © 2013 Elsevier Ltd.


Stewart A.K.,Mayo Clinic in Arizona | Trudel S.,Princess Margaret Hospital | Bahlis N.J.,Tom Baker Cancer Center | White D.,Health science Center | And 17 more authors.
Blood | Year: 2013

We conducted a randomized, controlled trial comparing thalidomide- prednisone as maintenance therapy with observation in 332 patients who had undergone autologous stem cell transplantation with melphalan 200 mg/m2. The primary end point was overall survival (OS); secondary end points were myeloma-specific progression-free survival, progression-free survival, incidence of venous thromboembolism, and health-related quality of life (HRQoL). With a median follow-up of 4.1 years, no differences in OS between thalidomide- prednisone and observation were detected (respective 4-year estimates of 68% vs 60%, respectively; hazard ratio = 0.77; P = .18); thalidomide-prednisone was associated with superior myeloma-specific progression-free survival and progression-free survival (for both outcomes, the 4-year estimates were 32% vs 14%; hazard ratio = 0.56; P < .0001) and more frequent venous thromboembolism (7.3% vs none; P = .0004). Median survival after first disease recurrence was 27.7 months with thalidomide-prednisone and 34.1 months in the observation group. Nine second malignancies were observed with thalidomide-prednisone versus 6 in the observation group. Those allocated to thalidomideprednisone reported worse HRQoL with respect to cognitive function, dyspnea, constipation, thirst, leg swelling, numbness, dry mouth, and balance problems. We conclude that maintenance therapy with thalidomide-prednisone after autologous stem cell transplantation improves the duration of disease control, but is associated with worsening of patient-reported HRQoL and no detectable OS benefit. © 2013 by The American Society of Hematology.


Dranitsaris G.,Nelson Mandela Metropolitan University | Truter I.,Nelson Mandela Metropolitan University | Lubbe M.S.,North West University South Africa | Cottrell W.,Princess Margaret Hospital | And 2 more authors.
Journal of Evaluation in Clinical Practice | Year: 2012

Rationale, aims and objectives Value-based pricing has recently been discussed by international bodies as a means to estimate a drug price that is linked to the benefits it offers patients and society. The World Health Organization (WHO) has recommended using three times a country's per capita gross domestic product (GDP) as the threshold for economic value. Using the WHO criteria, pharmacoeconomic modelling was used to illustrate the application of value-based price towards bevacizumab, a relatively new drug that provides a 1.4-month survival benefit to patients with metastatic colorectal cancer (mCRC). Methods A decision model was developed to simulate outcomes in mCRC patients receiving chemotherapy ± bevacizumab. Clinical data were obtained from randomized trials and costs from Canadian cancer centres. Utility estimates were determined by interviewing 24 oncology nurses and pharmacists. A price per dose of bevacizumab was then estimated using a target threshold of $CAD117 000 per quality adjusted life year gained, which is three times the Canadian per capita GDP. Results For a 1.4-month survival benefit, a price of $CAD830 per dose would be considered cost-effective from the Canadian public health care perspective. If the drug were able to improve patient quality of life or survival from 1.4 to 3 months, the drug price could increase to $CAD1560 and $CAD2180 and still be considered cost-effective. Discussion The use of the WHO criteria for estimating a value-based price is feasible, but a balance between what patients/governments can afford to pay and the commercial viability of the product in the reference country would be required. © 2010 Blackwell Publishing Ltd.


Basu P.,Chittaranjan National Cancer Institute | Chandna P.,AceProbe Technologies India Pvt. Ltd. | Bamezai R.N.K.,Jawaharlal Nehru University | Siddiqi M.,Cancer Foundation of India | And 3 more authors.
Journal of Clinical Microbiology | Year: 2011

Type-specific detection of human papillomavirus (HPV) is indicated for better risk stratification and clinical management of women testing positive for HPV and for epidemiologic surveillance. MassARRAY spectrometry (MassARRAY; Sequenom) is a novel method for type-specific detection of 15 high-risk oncogenic HPV types: HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66, -68, and -73. PreTect HPV-Proofer (Proofer; Norchip) is a type-specific assay that detects E6/E7 mRNA from five high-risk oncogenic HPV types: HPV-16, -18, -31, -33, and -45. The performance of these tests for type-specific identification of HPV was assessed with cervical specimens from 192 cases of cervical cancer in comparison with consensus MY09/MY11 PCR followed by nucleotide sequencing (consensus PCR). The overall HPV detection rates were 94.8% (95% confidence interval [CI], 91.7, 97.9), 83.3% (95% CI, 78.1, 88.5), and 86.5% (95% CI, 81.7, 91.3) for MassARRAY, Proofer, and consensus PCR, respectively. All tests were negative in six (3.1%) of the 192 cases. Considering only the specimens that contained at least one of the five types targeted by Proofer, the detection rates were 96.6%, 91.4%, and 86.9% for MassARRAY, Proofer, and consensus PCR, respectively. MassARRAY detected multiple infections in 14.1%, Proofer detected multiple infections in 3.6%, and consensus PCR failed to detect any multiple infections. The agreement was highest at 86.0% (kappa = 0.76) between MassARRAY and Proofer and lowest at 81.8% (kappa = 0.69) between Proofer and consensus PCR. In conclusion, MassARRAY is a highly sensitive and accurate method for type-specific detection of oncogenic HPV in cervical cancer, with Proofer showing impressive performance. Copyright © 2011, American Society for Microbiology. All Rights Reserved.


Ratnam S.,Public Health Laboratory | Ratnam S.,Memorial University of Newfoundland | Coutlee F.,University of Montréal | Fontaine D.,Memorial University of Newfoundland | And 9 more authors.
Journal of Clinical Microbiology | Year: 2011

Detection of human papillomavirus (HPV) E6/E7 oncogene expression may be more predictive of cervical cancer risk than testing for HPV DNA. The Aptima HPV test (Gen-Probe) detects E6/E7 mRNA of 14 oncogenic types. Its clinical performance was compared with that of the Hybrid Capture 2 DNA test (HC2; Qiagen) in women referred for colposcopy and those routinely screened. Aptima was also compared with the PreTect HPV-Proofer E6/E7 mRNA assay (Proofer; Norchip) in the referral population. Cervical specimens collected in PreservCyt (Hologic Inc.) were processed for HPV detection and genotyping with the Linear Array (LA) method (Roche Molecular Diagnostics, Laval, Quebec, Canada). Histology-confirmed high-grade cervical intraepithelial neoplasia (CIN 2) or worse (CIN 2+) served as the disease endpoint. On the basis of 1,418 referral cases (CIN 2+, n = 401), the sensitivity of Aptima was 96.3% (95% confidence interval [CI], 94.4, 98.2), whereas it was 94.3% (95% CI, 92.0, 96.6) for HC2. The specificities were 43.2% (95% CI, 40.2, 46.2) and 38.7% (95% CI, 35.7, 41.7), respectively (P < 0.05). In 1,373 women undergoing routine screening (CIN 2+, n = 7), both Aptima and HC2 showed 100% sensitivity, and the specificities were 88.3% (95% CI, 86.6, 90.0) and 85.3% (95% CI, 83.5, 87.3), respectively (P < 0.05); for women ≥30 years of age (n = 845), the specificities were 93.9% (95% CI, 92.3, 95.5) and 92.1% (95% CI, 90.3, 93.9), respectively (P < 0.05). On the basis of 818 referral cases (CIN 2+, n = 235), the sensitivity of Aptima was 94.9% (95% CI, 92.1, 97.7) and that of Proofer was 79.1% (95% CI, 73.9, 84.3), and the specificities were 45.8% (95% CI, 41.8, 49.8) and 75.1% (95% CI, 71.6, 78.6), respectively (P < 0.05). Both Aptima and Proofer showed a higher degree of agreement with LA genotyping than HC2. In conclusion, the Aptima test is as sensitive as HC2 but more specific for detecting CIN 2+ and can serve as a reliable test for both primary cervical cancer screening and the triage of borderline cytological abnormalities. Copyright © 2011, American Society for Microbiology. All Rights Reserved.


Ratnam S.,Public Health Laboratory | Ratnam S.,Memorial University of Newfoundland | Coutlee F.,University of Montréal | Fontaine D.,Memorial University of Newfoundland | And 9 more authors.
Journal of Clinical Microbiology | Year: 2010

Human papillomavirus (HPV) DNA testing has a higher clinical sensitivity than cytology for the detection of high-grade cervical intraepithelial neoplasia or worse (CIN 2+). However, an improvement in specificity would be desirable. As malignant transformation is induced by HPV E6/E7 oncogenes, detection of E6/E7 oncogene activity may improve specificity and be more predictive of cervical cancer risk. The PreTect HPV-Proofer assay (Proofer; Norchip) detects E6/E7 mRNA transcripts from HPV types 16, 18, 31, 33, and 45 with simultaneous genotype-specific identification. The clinical performance of this assay was assessed in a cross-sectional study of women referred for colposcopy in comparison with the Hybrid Capture 2 (HC2; Qiagen) test, which detects DNA of 13 high-risk oncogenic HPV types collectively. Cervical specimens were collected in PreservCyt, and cytology was performed using the ThinPrep method (Hologic). The samples were processed for HPV detection with Proofer and HC2 and genotyping with the Linear Array method (Roche Molecular Systems). Histology-confirmed CIN 2+ served as the disease endpoint to assess the clinical performance of the tests. A total of 1,551 women were studied, and of these, 402 (25.9%) were diagnosed with CIN 2+ on histology. The Proofer assay showed a sensitivity of 78.1% (95% confidence interval [CI], 74.1 to 82.1) versus 95.8% (95% CI, 93.8 to 97.8) for HC2 (P < 0.05) and a specificity of 75.5% (95% CI, 73.0 to 78.0) versus 39.6% (95% CI, 36.8 to 42.4), respectively (P < 0.05). The lower sensitivity and higher specificity of Proofer for detection of CIN 2+ can be attributed to the fact that this test detects the expression of E6/E7 genes beyond a threshold from a limited number of oncogenic HPV types. In conclusion, Proofer is more specific than HC2 in identifying women with CIN 2+ but has a lower sensitivity. Copyright © 2010, American Society for Microbiology. All Rights Reserved.


PubMed | University of Calgary, The Ottawa Hospital Rehabilitation Center, University of Ottawa, University of British Columbia and 5 more.
Type: Journal Article | Journal: BMJ supportive & palliative care | Year: 2016

The desire for death in terminally ill patients is associated with depression and anxiety, but not all patients who report it meet criteria for mental disorders. We examined the characteristics of subgroups of palliative cancer patients who expressed a desire for death that occurred either with or without a concurrent depressive or anxiety disorder.Cross-sectional survey.Eight Canadian palliative care programs.377 patients with cancer.Desire for Death Rating Scale; Structured Interview of Symptoms and Concerns.Most participants (69.5%) had no desire for death. Of the remainder, 69 (18.3%) acknowledged occasional transient thoughts, and 46 (12.2%) reported an apparently genuine desire to die. In the latter group, 24 individuals (52.2%) were diagnosed with a mental disorder and 22 (44.8%) were not. Individuals with no serious desire for death and no mental disorder reported the least distress in physical, social, existential, and psychological symptoms and concerns; those with a mental disorder and a significant desire for death reported the most. The subgroup of patients with a serious desire for death but no concurrent mental disorders still reported increased distress due to physical symptoms and social concerns, as well as a higher prevalence of global suffering.The expression of a desire for death by a terminally ill patient should raise a suspicion about mental health problems, but is not in itself clearly indicative of one. Nevertheless, it may serve as a catalyst to review the individuals physical symptom management and interpersonal concerns, and overall sense of suffering.


Abbott R.,Dr iss Murphy Cancer Center | Edwards S.,Dr iss Murphy Cancer Center | Whelan M.,Dr iss Murphy Cancer Center | Edwards J.,Dr iss Murphy Cancer Center | Dranitsaris G.,Consultant in Health Economics and Biostatistics
Journal of Oncology Pharmacy Practice | Year: 2014

Purpose: Oral anticancer agents offer significant benefits over parenteral anticancer therapy in terms of patient convenience and reduced intrusiveness. Oral anticancer agents give many cancer patients freedom from numerous hospital visits, allowing them to obtain their medications from their local community pharmacy. However, a major concern with increased use of oral anticancer agents is shift of responsibility in ensuring the proper use of anticancer agents from the hospital/clinical oncology team to the patient/caregiver and other healthcare providers such as the community pharmacists who may not be appropriately trained for this. This study assessed the readiness of community pharmacists across Canada to play this increased role with respect to oral anticancer agents. Methods: Using a structured electronic mailing strategy, a standardized survey was mailed to practicing pharmacists in five provinces where community pharmacists were dispensing the majority of oral anticancer agents. In addition to collecting basic demographic and their practice setting, the survey assessed the pharmacists knowledge regarding cancer therapy and oral anticancer agents in particular, their education needs and access to resources on oral anticancer agents, the quality of prescriptions for oral anticancer agents received by them in terms of the required elements, their role in patient education, and steps to enhance patient and personal safety. Results: There were 352 responses to the survey. Only 13.6% of respondents felt that they had received adequate oncology education at the undergraduate level and approximately 19% had attended a continuing education event related to oncology in the past 2 years. Only 24% of the pharmacists who responded were familiar with the common doses of oral anticancer agents and only 9% felt comfortable educating patients on these medications. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.


Dranitsaris G.,Dr iss Murphy Cancer Center | Edwards S.,Dr iss Murphy Cancer Center | Edwards J.,Dr iss Murphy Cancer Center | Leblanc M.,Dr iss Murphy Cancer Center | Abbott R.,Dr iss Murphy Cancer Center
Current Oncology | Year: 2010

In 2005, bevacizumab was approved by Health Canada for patients with metastatic colorectal cancer (mcrc). Newfoundland and Labrador was one of the first Canadian provinces to fund this agent in combination with folfiri (irinotecan, 5-fluorouracil, leucovorin) chemotherapy. In this analysis, the entire provincial bevacizumab sample for the first 2 years was assessed for overall safety and efficacy. Methods The medical records of 43 patients with mcrc who had received folfiri with bevacizumab were identified and reviewed. The longitudinal data collection format that was adopted assessed occurrences of adverse events after each cycle of treatment. Toxicity outcomes such as gastrointestinal (gi) perforations, bleeding, diarrhea, myelosuppression, proteinuria, and venous thromboembolic events (VTEs) were collected and graded using the U.S. National Cancer Institute's Common Terminology Criteria for Adverse Events, version 3.0. Time to treatment failure (TTF) and overall survival (OS) were determined using the Kaplan-Meier method. Results Overall, the 43 study patients received 398 cycles of anticancer therapy (median: 6 cycles; range: 1-24 cycles). No gi perforations were identified. However, 4 bleeding events occurred (9.3%), 3 requiring permanent discontinuation of bevacizumab. Also, 6 grade 3 or 4 VTEs occurred (14.0%), 3 of which required a hospital admission. In addition, grades 3 and 4 diarrhea, febrile neutropenia, and proteinuria showed cumulative incidences of 11.6%, 2.3%, and 2.3% respectively. Median ttf was 6.3 months; median os was 24.4 months. Conclusions Bevacizumab in combination with folfiri appears to be well tolerated, and efficacy is consistent with trial reports. However, patients should be closely monitored to avoid potentially serious events such as bleeding and VTEs. © 2010 Multimed Inc.


Belyea R.,Dr iss Murphy Cancer Center
Journal of Medical Imaging and Radiation Sciences | Year: 2011

Recent advances in the field of genetics have resulted in the ability to perform genetic tests on individuals to estimate their risk of developing certain diseases. This predictive testing can be used to determine the presence or absence of a specific genetic factor for types of breast, ovarian, colorectal, stomach, and ocular cancers. This article will discuss genetic testing for the cancers listed, including issues surrounding positive results; common issues that arise surrounding genetic testing; what to do when given the results; and what are the available preventative measures. © 2011 Published by Elsevier Inc.

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