Castellano D.,University Hospital 12 Of Octubre |
Bajetta E.,Istituto di Oncologia |
Panneerselvam A.,Novartis |
Saletan S.,Novartis |
And 4 more authors.
Oncologist | Year: 2013
Introduction. The incidence of colorectal neuroendocrine tumors(NETs) is increasing,andpatients with this disease have particularly poor prognoses. Treatment options are limited, and survival times have not improved in the past decade. Methods. A post hoc analysis of the efficacy and tolerability of everolimus plus octreotide long-acting repeatable (LAR) was conducted in patients with colorectal NETs enrolled in the phase III RAD001 in Advanced Neuroendocrine Tumors, Second Trial (RADIANT-2) study. The primary endpoint (progression- free survival [PFS]), secondary endpoints (including objective response rate), and safety were assessed. Results. Patients with colorectal NETs receiving everolimus plus octreotide LAR had a significantly longer median PFS (29.9 months; n=19) than did those receiving placebo plus octreotide LAR (6.6 months; n = 20). Everolimus plus octreotide LAR treatment also significantly reduced the risk for disease progression (hazard ratio: 0.34; 95% confidence interval: 0.13- 0.89; p=.011). Although no objective responses were observed, tumor shrinkage was more frequently noted in theeverolimusplusoctreotideLARarmthanintheplaceboplus octreotide LAR arm (67% vs. 37%, respectively). The combination of everolimus plus octreotideLARwasgenerally well tolerated by patients with colorectal NETs; rash and stomatitis were the most commonly reported adverse events. Conclusions. Everolimus plus octreotide LAR treatment had significant benefits and improved outcomes for patients with advanced colorectal NETs compared with placebo plus octreotide LAR treatment. Results of this exploratory analysis are consistent with those reported from the RADIANT-2 primary analysis. These findings support additional investigations of everolimus plus octreotide LAR in patients with colorectal NETs. © AlphaMed Press.
Ezeife D.A.,Tom Baker Cancer Center |
Truong T.H.,University of Calgary |
Heng D.Y.C.,Tom Baker Cancer Center |
Bourque S.,British Columbia Cancer Agency |
And 2 more authors.
Cancer | Year: 2015
BACKGROUND The drug approval timeline is a lengthy process that often varies between countries. The objective of this study was to delineate the Canadian drug approval timeline for oncology drugs and to compare the time to drug approval between Health Canada (HC) and the US Food and Drug Administration (FDA). METHODS In total, 54 antineoplastic drugs that were approved by the FDA between 1989 and 2012 were reviewed. For each drug, the following milestones were determined: the dates of submission and approval for both the FDA and HC and the dates of availability on provincial drug formularies in Canadian provinces and territories. The time intervals between the aforementioned milestones were calculated. RESULTS Of 54 FDA-approved drugs, 49 drugs were approved by HC at the time of the current study. The median time from submission to approval was 9 months (interquartile range [IQR], 6-14.5 months) for the FDA and 12 months (IQR, 10-21.1 months) for HC (P < .0006). The time from HC approval to the placement of a drug on a provincial drug formulary was a median of 16.7 months (IQR, 5.9-27.2 months), and there was no interprovincial variability among the 5 Canadian provinces that were analyzed (P = .5). CONCLUSIONS The time from HC submission to HC approval takes 3 months longer than the same time interval for the FDA. To the authors' knowledge, this is the first documentation of the time required to bring an oncology drug from HC submission to placement on a provincial drug formulary. Cancer 2015;121:1688-1693. © 2015 American Cancer Society.
Donnelly B.J.,Tom Baker Cancer Center |
Saliken J.C.,Nanaimo Regional Hospital |
Brasher P.M.A.,Center for Clinical Epidemiology and Evaluation |
Ernst S.D.,London Regional Cancer Center |
And 5 more authors.
Cancer | Year: 2010
BACKGROUND: Localized prostate cancer can be treated several different ways, but head-to-head comparisons of treatments are infrequent. The authors of this report conducted a randomized, unblinded, noninferiority trial to compare cryoablation with external beam radiotherapy in these patients. METHODS: From December 1997 through February 2003, 244 men with newly diagnosed localized prostate cancer were assigned randomly to receive either cryoablation or radiotherapy (122 men in each arm). All received neoadjuvant antiandrogen therapy. The primary endpoint was disease progression at 36 months based on a trifecta definition: 1) radiologic evidence of metastatic disease, or 2) initiation of further antineoplastic therapy, or 3) biochemical failure. Two definitions of biochemical failure were used: 1) 2 consecutive rises in prostate-specific antigen (PSA) with a final value >1.0 ng/mL, and 2) a rise above PSA nadir + 2 ng/mL. Secondary endpoints included overall survival, disease-specific survival, and prostate biopsy at 36 months. RESULTS: The median follow-up was 100 months. Disease progression at 36 months was observed in 23.9% (PSA nadir + 2 ng/mL, 17.1%) of men in the cryoablation arm and in 23.7% (PSA nadir + 2 ng/mL, 13.2%) of men in the radiotherapy arm. No difference in overall or disease-specific survival were observed. At 36 months, more patients in the radiotherapy arm had a cancer-positive biopsy (28.9%) compared with patients in the cryoablation arm (7.7%). CONCLUSIONS: The observed difference in disease progression at 36 months was small, 0.2%; however, because of the wide confidence interval, from -10.8% to 11.2%, it was not possible to rule out inferiority (defined a priori as a 10% difference). With longer term follow-up, the trend favors cryoablation. Significantly fewer positive biopsies were documented after cryoablation than after radiotherapy. © 2010 American Cancer Society.
Bauman G.,University of Western Ontario |
Rumble R.B.,Cancer Care Ontarios Program in Evidence Based Care |
Chen J.,London Regional Cancer Center |
Loblaw A.,Sunnybrook Health science Center |
Warde P.,Radiation Treatment Program
Clinical Oncology | Year: 2012
Three-dimensional conformal radiotherapy (3DCRT) as the primary treatment for prostate cancer has improved outcomes compared with conventional radiotherapy, but with an associated increase in toxicity due to radiation effects on the bladder and rectum. Intensity-modulated radiotherapy (IMRT) is a newer method of radiotherapy that uses intensity-modulated beams that can provide multiple intensity levels for any single beam direction and any single source position allowing concave dose distributions and dose gradients with narrower margins than those possible using conventional methods. IMRT is ideal for treating complex treatment volumes and avoiding close proximity organs at risk that may be dose limiting and provides increased tumour control through an escalated dose and reduces normal tissue complications through organ at risk sparing. Given the potential advantages of IMRT and the availability of IMRT-enabled treatment planning systems and linear accelerators, IMRT has been introduced in a number of disease sites, including prostate cancer. This systematic review examined the evidence for IMRT in the treatment of prostate cancer in order to quantify the potential benefits of this new technology and to make recommendations for radiation treatment programmes considering adopting this technique. The findings were in favour of recommending IMRT over 3DCRT in the radical treatment of localised prostate cancer where doses greater than 70 Gy are required, based on a review of 11 published reports including 4559 patients. There were insufficient data to recommend IMRT over 3DCRT in the postoperative setting. Future research should examine image-guided IMRT in the post-prostatectomy setting, with altered fractionation, and in combination with hormone and chemotherapy. © 2012.
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.