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Bells Corners, Canada

Sridhar S.S.,University of Toronto | Canil C.M.,Ottawa Regional Cancer Center | Chi K.N.,BC Cancer Agency | Hotte S.J.,Juravinski Cancer Center | And 8 more authors.
Cancer Chemotherapy and Pharmacology | Year: 2011

Purpose: GTI-2040 is a novel antisense oligonucleotide to the R2 subunit of ribonucleotide reductase. This phase II trial was conducted to determine the efficacy and tolerability of GTI-2040 when combined with docetaxel and prednisone for the treatment of patients with castration-resistant prostate cancer (CRPC). Methods: Chemo-naïve CRPC patients with adequate performance status and organ function were treated with docetaxel 75 mg/m2 IV on day 1 plus GTI-2040 5 mg/kg/day by continuous intravenous infusion day 1-14 on a 21 day cycle, with prednisone 5 mg orally twice daily. The primary endpoint was PSA response rate. Pharmacokinetic studies of GTI-2040 and pharmacodynamic studies on peripheral blood mononuclear cells (PBMC) were also performed. Results: Twenty-two patients in total (19 from this study and 3 from a prior phase I/II study at this institution) were treated at the recommended phase II dose. A confirmed PSA response was seen in 9/22 patients (41%). Of 16 patients with measurable disease, there was 1 partial response (PR) and 12 stable disease (SD) lasting 3.6 months (median), as best response. The most common toxicities were anemia, fatigue, lymphopenia, leucopenia and neutropenia. Grade 3+ toxicities included neutropenia, lymphopenia, leucopenia, fatigue, febrile neutropenia and hypophosphatemia. Conclusions: The PSA response rate of GTI-2040 in combination with docetaxel and prednisone just met the minimum phase II criteria for further enrollment. However, after evaluation of all the clinical data, further study of this dose and schedule of GTI-2040 in CRPC was not recommended. © 2010 Springer-Verlag. Source

Bosse D.,Universite de Sherbrooke | Vickers M.,Ottawa Regional Cancer Center | Lemay F.,Universite de Sherbrooke | Beaudoin A.,Universite de Sherbrooke
Current Oncology | Year: 2015

Background Metastatic colorectal cancer (MCRC) commonly affects elderly people, an understudied subset of patients. We analyzed the survival impact of the first and subsequent lines of chemotherapy in eligible non-trial patients 70 years of age and older with mcrc treated between 2004 and 2012. Methods This single-centre retrospective analysis estimated overall survival (OS) and progression-free survival (PFS) using the Kaplan–Meier method. Multivariate analysis was used to adjust for age, sex, Eastern Cooperative Oncology Group performance status, score on the Charlson comorbidity index, dependency in activities of daily living, and exposure to 1 or more chemotherapy doublets, capecitabine alone, or best supportive care (BSc.). Results Of 109 patients identified, 29 elected BSc., and 80 received chemotherapy. In multivariate analysis, age was not associated with os [hazard ratio (HR): 0.99; 95% confidence interval (CI): 0.92 to 1.05], but a performance status of 2 or higher was associated with a decreased likelihood of survival (HR: 3.12; 95% CI: 1.87 to 5.76), and exposure to 1 or more doublets was associated with improved survival (HR: 0.33; 95% CI: 0.17 to 0.66). In univariate analysis, a trend toward improved os was observed for first-line doublet chemotherapy compared with capecitabine (HR: 0.66; 95% ci: 0.41 to 1.07), and pfs was superior (HR: 0.46; 95% CI: 0.26 to 0.84). Compared with exposure to 1 doublet, exposure to the 3 potential cytotoxic chemotherapies was not associated with improved os (HR: 0.77; 95% CI: 0.41 to 1.43). The incidence of neutropenia with first-line folfiri was 40%; the incidences of bevacizumab-related arterial and venous thrombosis were both 8%. Conclusions Exposure to 1 or more doublet chemotherapies for mcrc was associated with better outcomes in non-trial patients 70 years of age and older. Elderly patients treated with palliative chemotherapy and bevacizumab should be monitored carefully for arterial and venous thrombotic events. © 2015 Multimed Inc. Source

Dimillo J.,McGill University | Samson A.,University of Ottawa | Theriault A.,University of Ottawa | Lowry S.,Womens Breast Health Center | And 6 more authors.
Psychology, Health and Medicine | Year: 2013

Women carrying a BRCA1 or BRCA2 genetic mutation have an up to 80% lifetime risk of developing breast cancer. It is especially important to understand the experiences of these women, as their lives are permeated with the threat of cancer. This qualitative study examined the experiences of six young women of reproductive age (age < 45 years) who were identified as carriers. The analysis of the semi-structured interviews inspired by grounded theory methodology, showed that participants experienced the same type of uncertainty demonstrated by women who have already been diagnosed with breast cancer. © 2013 Copyright Taylor and Francis Group, LLC. Source

Palma D.A.,London Regional Cancer Program | Haasbeek C.J.A.,VU University Amsterdam | Rodrigues G.B.,London Regional Cancer Program | Dahele M.,VU University Amsterdam | And 7 more authors.
BMC Cancer | Year: 2012

Background: Stereotactic ablative radiotherapy (SABR) has emerged as a new treatment option for patients with oligometastatic disease. SABR delivers precise, high-dose, hypofractionated radiotherapy, and achieves excellent rates of local control. Survival outcomes for patients with oligometastatic disease treated with SABR appear promising, but conclusions are limited by patient selection, and the lack of adequate controls in most studies. The goal of this multicenter randomized phase II trial is to assess the impact of a comprehensive oligometastatic SABR treatment program on overall survival and quality of life in patients with up to 5 metastatic cancer lesions, compared to patients who receive standard of care treatment alone.Methods: After stratification by the number of metastases (1-3 vs. 4-5), patients will be randomized between Arm 1: current standard of care treatment, and Arm 2: standard of care treatment + SABR to all sites of known disease. Patients will be randomized in a 1:2 ratio to Arm 1:Arm 2, respectively. For patients receiving SABR, radiotherapy dose and fractionation depends on the site of metastasis and the proximity to critical normal structures. This study aims to accrue a total of 99 patients within four years. The primary endpoint is overall survival, and secondary endpoints include quality of life, toxicity, progression-free survival, lesion control rate, and number of cycles of further chemotherapy/systemic therapy.Discussion: This study will provide an assessment of the impact of SABR on clinical outcomes and quality of life, to determine if long-term survival can be achieved for selected patients with oligometastatic disease, and will inform the design of a possible phase III study.Trial registration: Clinicaltrials.gov identifier: NCT01446744. © 2012 Palma et al.; licensee BioMed Central Ltd. Source

Whelan T.J.,McMaster University | Pignol J.-P.,Odette Cancer Center | Levine M.N.,McMaster University | Julian J.A.,McMaster University | And 10 more authors.
New England Journal of Medicine | Year: 2010

BACKGROUND: The optimal fractionation schedule for whole-breast irradiation after breast-conserving surgery is unknown. METHODS: We conducted a study to determine whether a hypofractionated 3-week schedule of whole-breast irradiation is as effective as a 5-week schedule. Women with invasive breast cancer who had undergone breast-conserving surgery and in whom resection margins were clear and axillary lymph nodes were negative were randomly assigned to receive whole-breast irradiation either at a standard dose of 50.0 Gy in 25 fractions over a period of 35 days (the control group) or at a dose of 42.5 Gy in 16 fractions over a period of 22 days (the hypofractionated-radiation group). RESULTS: The risk of local recurrence at 10 years was 6.7% among the 612 women assigned to standard irradiation as compared with 6.2% among the 622 women assigned to the hypofractionated regimen (absolute difference, 0.5 percentage points; 95% confidence interval [CI], -2.5 to 3.5). At 10 years, 71.3% of women in the control group as compared with 69.8% of the women in the hypofractionated-radiation group had a good or excellent cosmetic outcome (absolute difference, 1.5 percentage points; 95% CI, -6.9 to 9.8). CONCLUSIONS: Ten years after treatment, accelerated, hypofractionated whole-breast irradiation was not inferior to standard radiation treatment in women who had undergone breast-conserving surgery for invasive breast cancer with clear surgical margins and negative axillary nodes. (ClinicalTrials.gov number, NCT00156052.) Copyright © 2010 Massachusetts Medical Society. Source

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