Selumetinib in patients receiving standard pemetrexed and platinum-based chemotherapy for advanced or metastatic KRAS wildtype or unknown non-squamous non-small cell lung cancer: A randomized, multicenter, phase II study. Canadian Cancer Trials Group (CCTG) IND.219.

Introduction: Activation of the RAS/RAF/MEK/ERK pathway may confer resistance to chemotherapy in non-small cell lung cancer (NSCLC). Selumetinib (AZD6244, ARRY142886), a MEK1/2 inhibitor combined with chemotherapy in patients with NSCLC was evaluated in two schedules to evaluate efficacy and toxicity.

Methods: IND.

A phase I study of foretinib plus erlotinib in patients with previously treated advanced non-small cell lung cancer: Canadian cancer trials group IND.196.

Purpose: MET and AXL mediate resistance to EGFR TKI in NSCLC. Foretinib, a MET/RON/AXL/TIE-2/VEGFR kinase inhibitor may overcome EGFR kinase resistance. This dose escalation study combined foretinib and erlotinib in advanced pretreated NSCLC patients.

ASCENDE-RT: An Analysis of Treatment-Related Morbidity for a Randomized Trial Comparing a Low-Dose-Rate Brachytherapy Boost with a Dose-Escalated External Beam Boost for High- and Intermediate-Risk Prostate Cancer.

Purpose: To report the genitourinary (GU) and gastrointestinal (GI) morbidity and erectile dysfunction in a randomized trial comparing 2 methods of dose escalation for high- and intermediate-risk prostate cancer.

Methods And Materials: ASCENDE-RT (Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy) enrolled 398 men, median age 68 years, who were then randomized to either a standard arm that included 12 months of androgen deprivation therapy and pelvic irradiation to 46 Gy followed by a dose-escalated external beam radiation therapy (DE-EBRT) boost to 78 Gy, or an experimental arm that substituted a low-dose-rate prostate brachytherapy (LDR-PB) boost. At clinic visits, investigators recorded GU and GI morbidity and information on urinary continence, catheter use, and erectile function.

Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (the ASCENDE-RT Trial): An Analysis of Survival Endpoints for a Randomized Trial Comparing a Low-Dose-Rate Brachytherapy Boost to a Dose-Escalated External Beam Boost for High- and Intermediate-risk Prostate Cancer.

Purpose: To report the primary endpoint of biochemical progression-free survival (b-PFS) and secondary survival endpoints from ASCENDE-RT, a randomized trial comparing 2 methods of dose escalation for intermediate- and high-risk prostate cancer.

Methods And Materials: ASCENDE-RT enrolled 398 men, with a median age of 68 years; 69% (n=276) had high-risk disease. After stratification by risk group, the subjects were randomized to a standard arm with 12 months of androgen deprivation therapy, pelvic irradiation to 46 Gy, followed by a dose-escalated external beam radiation therapy (DE-EBRT) boost to 78 Gy, or an experimental arm that substituted a low-dose-rate prostate brachytherapy (LDR-PB) boost.

A Phase II Study of PF-03446962 in Patients with Advanced Malignant Pleural Mesothelioma. CCTG Trial IND.207.

There is no approved second-line systemic therapy option for malignant pleural mesothelioma (MPM), but targeting angiogenesis is an area of investigation. PF-03446962 is a fully human antibody against activin receptor-like kinase 1, which is commonly expressed in tumor vasculature. We performed a multicenter, open label, single-arm, two-stage phase II study of PF-03446962 in patients with MPM and progressive disease after platinum-based chemotherapy.

Pan Canadian Rash Trial: A Randomized Phase III Trial Evaluating the Impact of a Prophylactic Skin Treatment Regimen on Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor-Induced Skin Toxicities in Patients With Metastatic Lung Cancer.

Purpose: Erlotinib is an epidermal growth factor receptor inhibitor approved for patients with advanced non-small-cell lung cancer (NSCLC) whose epidermal growth factor receptor expression status is positive or unknown. Although it is efficacious, erlotinib can cause skin toxicity. This prospective, randomized phase III trial examined the effect of prophylactic treatment of erlotinib-induced skin rash.

The Influence of the Evolution of First-Line Chemotherapy on Steadily Improving Survival in Advanced Non-Small-Cell Lung Cancer Clinical Trials.

Over the past three decades, survival in advanced non-small-cell lung cancer (NSCLC) clinical trials has doubled with an increase in 1-year survival from 25% to 50 to 55%. This has been mainly attributed to improvements in systemic therapy. Although modern first-line chemotherapy regimens have more favorable toxicity profiles, a statistically significant improvement in overall survival has not been demonstrated in existing meta-analyses of second-generation versus third-generation combinations.

Evaluation of second-line and subsequent targeted therapies in metastatic renal cell cancer (mRCC) patients treated with first-line cediranib.

Introduction: Pivotal phase III trials have positioned angiogenesis inhibitors as first-line therapy for the management of most advanced or metastatic renal cell carcinomas (mRCC). Approaches to second-line therapy, however, remain more controversial with respect to drug selection and drug sequencing.

Methods: In this study we evaluated mRCC patients who were initially treated on the first-line National Cancer Institute (NCI) trial with the highly potent vascular endothelial growth factor receptor tyrosine kinase inhibitor (TKI), cediranib, to determine the efficacy and tolerability of subsequent therapies.

Referral patterns in advanced non-small cell lung cancer: impact on delivery of treatment and survival in a contemporary population based cohort.

Introduction: Chemotherapy improves overall survival (OS) in advanced non-small cell lung cancer (NSCLC), yet low rates of chemotherapy utilization have been observed. We sought to characterize the clinical effectiveness of chemotherapy in the general population by evaluating referral patterns, predictors of chemotherapy receipt and outcomes.

Methods: All referred cases of stage IIIB/IV NSCLC in British Columbia from January 1 to December 31, 2009 were retrospectively reviewed.

A retrospective, Canadian multi-center study examining the impact of prior response to abiraterone acetate on efficacy of docetaxel in metastatic castration-resistant prostate cancer.

Background: Questions about optimal sequencing of systemic therapy in metastatic castration-resistant prostate cancer (mCRPC) and whether cross-resistance occurs between different drugs remain largely unanswered. Previous studies have produced conflicting data on the activity of docetaxel in patients who did not attain a prostate-specific antigen (PSA) response to abiraterone acetate (abiraterone). We investigated whether the biochemical response to abiraterone is associated with efficacy of subsequent docetaxel therapy.

Less toxic chemotherapy improves uptake of all lines of chemotherapy in advanced non-small-cell lung cancer: a 10-year retrospective population-based review.

Background: Over the past decade, well tolerated second-line therapies for advanced non-small-cell lung cancer have been approved including erlotinib and pemetrexed in addition to docetaxel. We hypothesize that the introduction of less toxic chemotherapy has increased treatment of advanced non-small-cell lung cancer resulting in improved survival.

Methods: The BC Cancer Agency provides cancer care to 4.

Efficacy of enzalutamide following abiraterone acetate in chemotherapy-naive metastatic castration-resistant prostate cancer patients.

Background: The activity of enzalutamide after prior treatment with both abiraterone acetate (abiraterone) and docetaxel has been examined in several retrospective studies. However, limited data are available on the efficacy of enzalutamide following abiraterone in chemotherapy-naive patients with metastatic castration-resistant prostate cancer (mCRPC).

Objective: To compare the activity of enzalutamide after abiraterone in docetaxel-experienced and docetaxel-naive mCRPC patients.

A phase II study of GW786034 (pazopanib) with or without bicalutamide in patients with castration-resistant prostate cancer.

Introduction: Pazopanib is an oral vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor. In this randomized, open label phase II study, pazopanib alone or in combination with bicalutamide was evaluated in patients with chemotherapy-naive castration-resistant prostate cancer (CRPC).

Patients And Methods: Patients received either pazopanib 800 mg daily (arm A) or pazopanib 800 mg plus bicalutamide 50 mg daily (arm B).

Outcomes with abiraterone acetate in metastatic castration-resistant prostate cancer patients who have poor performance status.

Background: Although abiraterone acetate (abiraterone) has proven efficacy in two randomised phase 3 trials in metastatic castration-resistant prostate cancer (mCRPC), patients who had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥2 were either excluded or under-represented in these trials.

Objective: To compare outcomes in ECOG PS 0-1 and ≥2 in mCRPC patients treated with abiraterone.

Design, Setting, And Participants: Cancer registries from three Canadian centres were used to retrospectively identify mCRPC patients (postdocetaxel and docetaxel-naïve) treated with abiraterone.

Three primary testicular tumours: Trials and tribulations of testicular preservation.

Balancing recurrence risk, side effects and patient preference in the treatment of multiple metachronous testicular tumours can be challenging. We present the case of a young male patient who developed 3 different primary testicular neoplasms over an 8-year period, each associated with retroperitoneal lymphadenopathy requiring chemotherapy. The first tumour at age 19 was managed with radical orchiectomy.

A population-based review of the feasibility of platinum-based combination chemotherapy after tyrosine kinase inhibition in EGFR mutation positive non-small cell lung cancer patients with advanced disease.

Introduction: The IPASS trial demonstrated superior progression free survival for Asian, light/never smoking, advanced, pulmonary adenocarcinoma patients treated with first-line gefitinib compared to carboplatin/paclitaxel, of which 59% of those tested were epidermal growth factor receptor (EGFR) mutation positive. In IPASS 39% of gefitinib treated patients went on to receive platin based polychemotherapy. We hypothesized that in a population-based setting fewer patients receive second-line platin based chemotherapy than those enrolled in a clinical trial.

A phase II study of cediranib (AZD 2171) in treatment naive patients with progressive unresectable recurrent or metastatic renal cell carcinoma. A trial of the PMH phase 2 consortium.

Background: Inhibition of angiogenesis has emerged as an effective therapeutic strategy in metastatic renal cell cancer (mRCC). In this single arm phase 2 study, we evaluated the efficacy and tolerability of cediranib (AZD2171) a potent angiogenesis inhibitor in first line mRCC.

Methods: Eligible patients who had no prior systemic therapy received cediranib 45 mg orally once daily continuously.

Elevated expression of BIRC6 protein in non-small-cell lung cancers is associated with cancer recurrence and chemoresistance.

Introduction: Non-small-cell lung cancer (NSCLC) is an aggressive, highly chemoresistant disease. Reliable prognostic assays and more effective treatments are critically required. BIRC6 (baculoviral inhibitors of apoptosis proteins repeat-containing 6) protein is a member of the inhibitors of apoptosis protein family thought to play an important role in the progression or chemoresistance of many cancers.

Thymoma: a population-based study of the management and outcomes for the province of British Columbia.

Introduction: Thymomas are rare neoplasms with variable clinical behavior. Our primary study aim was to analyze treatment practices and outcomes in a population-based cohort of thymoma patients. We hypothesized that stage I and II thymomas would have high cure rates with resection and adjuvant radiation, whereas locally advanced cases would benefit from multimodality therapy.

Divergent genomic and epigenomic landscapes of lung cancer subtypes underscore the selection of different oncogenic pathways during tumor development.

For therapeutic purposes, non-small cell lung cancer (NSCLC) has traditionally been regarded as a single disease. However, recent evidence suggest that the two major subtypes of NSCLC, adenocarcinoma (AC) and squamous cell carcinoma (SqCC) respond differently to both molecular targeted and new generation chemotherapies. Therefore, identifying the molecular differences between these tumor types may impact novel treatment strategy.

Stage III non-small-cell lung cancer: population-based patterns of treatment in British Columbia, Canada.

Introduction: Management of Stage III non-small-cell lung cancer (NSCLC) involves surgery, radiotherapy (RT), chemotherapy, and best supportive care. The aims were to describe the patterns of treatment in a population-based cohort of patients, and compare utilization of RT and chemotherapy to model estimates of need.

Methods: Patients diagnosed with Stage III NSCLC between January 1, 2000, to December 31, 2007, were identified from the British Columbia Cancer Agency database.

A phase II pharmacodynamic study of preoperative figitumumab in patients with localized prostate cancer.

Purpose: Activation of the insulin-like growth factor 1 receptor (IGF-IR) is implicated in prostate cancer development and progression. This study evaluated biologic and clinical effects of figitumumab, a fully human monoclonal IGF-IR antibody, in patients with localized prostate cancer.

Experimental Design: Eligible patients received figitumumab 20 mg/kg intravenously every 3 weeks for 3 cycles followed by prostatectomy.