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Background: Lung cancer (LC) is the leading cause of cancer-related mortality. In Ontario, Canada, there are significant survival differences for patients with newly diagnosed LC across the 14 provincial regions. Methods: A population-based retrospective cohort study using ICES databases from 01/2007–12/2017 identified patients with newly diagnosed LC through the Ontario Cancer Registry and those with LC as the cause of death. Descriptive data included patient, disease, and system characteristics. The primary outcome was 5-year survival by region. Results: 178,202 patient records were identified; 101,263 met inclusion criteria. LC incidence varied by region (5.6–14.6/10,000), as did histologic subtype (adenocarcinoma: 27.3–46.1%). Five-year cancer-specific survival was impacted by age, rurality, pathologic subtype, stage at diagnosis, and income quintile. Timely care was inversely related to survival (fastest quintile: HR 3.22, p < 0.0001). Adjusted 5-year cancer-specific survival varied across regions (24.1%, HR 1.12; 34.0%, HR 0.89, p < 0.001). Conclusions: When adjusting for confounders, differences in survival by health region persisted, suggesting a complex interplay between patient, disease, and system factors. A single approach to improving patient care is likely to be ineffective across different systems. Quality improvement initiatives to improve patient outcomes require different approaches amongst health regions to address local disparities in care. [ABSTRACT FROM AUTHOR]

Aims: In 2014, in response to evidence that Canada's tobacco use would lead, inexorably, to substantial morbidity and mortality for the foreseeable future, a group of experts convened to consider the development of a "Tobacco Endgame" for Canada. The "Tobacco Endgame" defines a time frame in which to eliminate structural, political, and social dynamics that sustain tobacco use, leading to improved population health. Strategies: A series of Background Papers describing possible measures that could contribute to the creation of a comprehensive endgame strategy for Canada was prepared in advance of the National Tobacco Endgame Summit hosted at Queen's University in 2016. At the summit, agreement was reached to work together to achieve <5% tobacco use by 2035 (<5 by '35). A report of the proceedings was shared widely. Achievements: Progress since 2016 has been mixed. The Summit report was followed by a national forum convened by Health Canada in March 2017, and in 2018, the Canadian Government adopted "<5 × '35" tobacco use target in a renewed Canadian tobacco reduction strategy. Tobacco use has declined in the last 5 years, but at a rate slower than that which will be needed to achieve the <5 by '35 goal. There remain > 5 million smokers in Canada, signaling that smoking-related diseases will continue to be an enormous health burden. Furthermore, the landscape of new products (e-cigarettes and cannabis) has created additional risks and opportunities. Future directions: A bold, reinvigorated tobacco control strategy is needed that significantly advances ongoing policy developments, including full implementation of the key demand-reduction policies of the WHO Framework Convention on Tobacco Control. Formidable, new disruptive policies and regulations will be needed to achieve Canada's Endgame goal. [ABSTRACT FROM AUTHOR]

Bortezomib and gemcitabine have each shown activity as single agents in mantle cell lymphoma (MCL), which is incurable. The purpose of this phase II study was to determine the efficacy and safety of the previously unstudied combination of bortezomib and gemcitabine in patients with relapsed or refractory MCL. Patients were eligible if they had relapsed MCL with 1--3 prior therapies. Patients were treated with gemcitabine 1000 mg/m2 on days 1 and 8 and bortezomib 1.0 mg/m2 IV on days 1, 4, 8, and 11, on a 21-day schedule. Twenty-six patients were evaluable for toxicity and 25 for response. The overall response rate was 60%% and the median progression free survival was 11.4 months. The main adverse effects were hematological, with 40%% and 48%% of patients experiencing grade 3/4 thrombocytopenia and granulocytopenia, respectively. Bortezomib and gemcitabine is an active combination in relapsed and refractory MCL with clinically meaningful results. It offers a chemotherapy backbone to which other agents, less myelosuppressive, may be added. [ABSTRACT FROM AUTHOR]

We studied the activity of T138067-sodium in patients with malignant gliomas. T138067-sodium is a unique new chemotherapy agent that inhibits microtubule formation by binding irreversibly and specifically to β1, β2, and β4 isotypes of β-tubulin, causing cell arrest at G2/M and inducing apoptosis. Patients with recurrent anaplastic astrocytoma or glioblastoma multiforme were treated intravenously with 330 mg/m² of T138067-sodium weekly. Treatment was continued until the patient experienced either unacceptable toxicity or progressive disease. Patients had to have histologically proven glioma, have bidimensionally measurable disease at least 1 cm × 1 cm, and have received no more than one prior adjuvant chemotherapy. No chemotherapy or radiotherapy for recurrent disease was permitted. Nineteen patients entered the trial. One patient was found to be ineligible. There were two patients with anaplastic astrocytoma and 16 with glioblastoma multiforme. Only two patients had received prior adjuvant chemotherapy. The first seven patients had full pharmacokinetic sampling. No dose-limiting toxicity was seen, and pharmacokinetic results were consistent with those from nonglioma patients. The most common drug-related effects were fatigue (33%), nausea (28%), neutropenia (28%), and anorexia (17%). No patients stopped the study because of toxicity. No responses were seen in the 15 eligible patients who completed at least one cycle. Three patients had stable disease with a median duration of 2.6 months. Our results suggest that given in this dose and schedule T138067-sodium does not have activity in this population of anaplastic astrocytoma and glioblastoma multiforme. [ABSTRACT FROM AUTHOR]

Examines the activation of nuclear enzyme topoisomerase inhibitor topotecan in non-Hodgkin's lymphoma in Canada. Diffusion of large B-cell lymphoma; Induction of hematologic toxicity; Occurrence of myelosuppression.

Summary: Background: In 2004, a randomised phase III trial by the European Organisation for Research and Treatment of Cancer (EORTC) and National Cancer Institute of Canada Clinical Trials Group (NCIC) reported improved median and 2-year survival for patients with glioblastoma treated with concomitant and adjuvant temozolomide and radiotherapy. We report the final results with a median follow-up of more than 5 years. Methods: Adult patients with newly diagnosed glioblastoma were randomly assigned to receive either standard radiotherapy or identical radiotherapy with concomitant temozolomide followed by up to six cycles of adjuvant temozolomide. The methylation status of the methyl-guanine methyl transferase gene, MGMT, was determined retrospectively from the tumour tissue of 206 patients. The primary endpoint was overall survival. Analyses were by intention to treat. This trial is registered with Clinicaltrials.gov, number NCT00006353. Findings: Between Aug 17, 2000, and March 22, 2002, 573 patients were assigned to treatment. 278 (97%) of 286 patients in the radiotherapy alone group and 254 (89%) of 287 in the combined-treatment group died during 5 years of follow-up. Overall survival was 27·2% (95% CI 22·2–32·5) at 2 years, 16·0% (12·0–20·6) at 3 years, 12·1% (8·5–16·4) at 4 years, and 9·8% (6·4–14·0) at 5 years with temozolomide, versus 10·9% (7·6–14·8), 4·4% (2·4–7·2), 3·0% (1·4–5·7), and 1·9% (0·6–4·4) with radiotherapy alone (hazard ratio 0·6, 95% CI 0·5–0·7; p<0·0001). A benefit of combined therapy was recorded in all clinical prognostic subgroups, including patients aged 60–70 years. Methylation of the MGMT promoter was the strongest predictor for outcome and benefit from temozolomide chemotherapy. Interpretation: Benefits of adjuvant temozolomide with radiotherapy lasted throughout 5 years of follow-up. A few patients in favourable prognostic categories survive longer than 5 years. MGMT methylation status identifies patients most likely to benefit from the addition of temozolomide. Funding: EORTC, NCIC, Nélia and Amadeo Barletta Foundation, Schering-Plough. [Copyright &y& Elsevier]

Triapine is a novel small molecule ribonucleotide reductase inhibitor that showed activity in renal cell carcinoma (RCC) cell lines. Evaluating new agents with novel mechanisms remains of interest for patients with incurable RCC. This was a single-arm, multicentre phase II trial where Triapine was given at a schedule of 96 mg/m2 2-h infusion daily x 4 repeated every 2 weeks in patients with recurrent RCC. A median of four cycles of Triapine was administered to 19 eligible patients. One response was seen (7%.) Median time to progression was 3.6 months. Common adverse events (AEs) were grade 1-2, with fatigue in 74%, nausea in 68% and vomiting in 58%. However grade 3/4 neutropenia was seen in 79% and acute reactions of hypoxia, hypotension, methemoglobinemia were seen. Dose reductions/delays due to AEs were common with only 47% of patients receiving > 90% of planned dose intensity. The study closed, at the end of stage 1 as it did not meet the minimal efficacy criteria to proceed. Further evaluation of Triapine at this dose and schedule in patients with advanced kidney cancer is not recommended.

Purpose: Liposomal lurtotecan (OSI-211) is a liposomal formulation of the water-soluble topoisomerase I inhibitor lurtotecan (GI147211), which demonstrated superior levels of activity compared with topotecan in preclinical models. We studied two schedules of OSI-211 in a randomized design in relapsed ovarian cancer to identify the more promising of the two schedules for further study., Patients and Methods: Eligible patients had measurable epithelial ovarian, fallopian, or primary peritoneal cancer that was recurrent after one or two prior regimens of chemotherapy. Patients were randomly assigned to receive either arm A (OSI-211 1.8 mg/m(2)/d administered by 30-minute intravenous infusion on days 1, 2, and 3 every 3 weeks) or arm B (OSI-211 2.4 mg/m(2)/d administered by 30-minute intravenous infusion on days 1 and 8 every 3 weeks). The primary outcome measure was objective response, which was confirmed by independent radiologic review, and a pick the winner statistical design was used to identify the schedule most likely to be superior., Results: Eighty-one patients were randomized between October 2000 and September 2001. The hematologic toxic effects were greater on arm A than on arm B (grade 4 neutropenia, 51% v 22%, respectively), as was febrile neutropenia (26% v 2.4%, respectively). Of the 80 eligible patients, eight patients (10%) had objective responses; six responders (15.4%; 95% CI, 6% to 30%) were in arm A and two responders (4.9%; 95% CI, 1% to 17%) were in arm B., Conclusion: The OSI-211 daily for 3 days intravenous schedule met the statistical criteria to be declared the winner in terms of objective response. This schedule was also associated with more myelosuppression than the schedule of OSI-211 administered in arm B.