Publications by authors named "Quincy S C Chu"

Non-small-cell lung cancer (NSCLC) is a highly heterogeneous disease that is frequently associated with a host of known oncogenic alterations. Advances in molecular diagnostics and drug development have facilitated the targeting of novel alterations such that the majority of NSCLC patients have driver mutations that are now clinically actionable. The goal of this review is to gain insights into clinical research and development principles by summary, analysis, and discussion of data on agents targeting known alterations in oncogene-driven, advanced NSCLC beyond those in the and the .

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For patients with non-small-cell lung cancer (NSCLC) tumors without currently targetable molecular alterations, standard-of-care treatment is immunotherapy with anti-PD-(L)1 checkpoint inhibitors, alone or with platinum-doublet therapy. However, not all patients derive durable benefit and resistance to immune checkpoint blockade is common. Understanding mechanisms of resistance-which can include defects in DNA damage response and repair pathways, alterations or functional mutations in STK11/LKB1, alterations in antigen-presentation pathways, and immunosuppressive cellular subsets within the tumor microenvironment-and developing effective therapies to overcome them, remains an unmet need.

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Activating mutations in , in particular, a point mutation leading to a glycine-to-cysteine substitution at codon 12 (G12C), are among the most frequent genomic alterations in non-small cell lung cancer (NSCLC). Several agents targeting KRAS G12C have recently entered clinical development. Sotorasib, a first-in-class specific small molecule that irreversibly inhibits KRAS G12C, has since obtained Health Canada approval.

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Small-cell lung cancer (SCLC) is an aggressive, neuroendocrine tumour with high relapse rates, and significant morbidity and mortality. Apart from advances in radiation therapy, progress in the systemic treatment of SCLC had been stagnant for over three decades despite multiple attempts to develop alternative therapeutic options that could improve responses and survival. Recent promising developments in first-line and subsequent therapeutic approaches prompted a Canadian Expert Panel to convene to review evidence, discuss practice patterns, and reach a consensus on the treatment of extensive-stage SCLC (ES-SCLC).

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Article Synopsis
  • * An expert working group has recommended that all targetable genetic alterations in NSCLC should be tested at diagnosis and re-evaluated upon treatment resistance to ensure optimal management.
  • * The group emphasized the importance of clear reporting of testing results to help clinicians make informed treatment decisions, reflecting the ongoing evolution of targeted therapy options.
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Targeting the immune system, especially the PDL-1/PD-1 axis, has significantly improved the outcomes of metastatic lung cancer patients. However, only a portion of patients will benefit significantly from PD(L)1 therapeutics alone or in combination with either chemotherapy or anti-CTLA4 antibody. It is therefore important to study predictive biomarkers to help select the patients who will experience the most benefit from immunotherapy.

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In Canada, the therapeutic management of patients with advanced non-small cell lung cancer (NSCLC) with rare actionable mutations differs between provinces, territories, and individual centres based on access to molecular testing and funded treatments. These variations, together with the emergence of several novel mesenchymal-epithelial transition () factor-targeted therapies for the treatment of NSCLC, warrant the development of evidence-based consensus recommendations for the use of these agents. A Canadian expert panel was convened to define key clinical questions, review evidence, discuss practice recommendations and reach consensus on the treatment of advanced -altered NSCLC.

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Thyroid cancer is the most common type of endocrine malignancy. Cornerstones of thyroid cancer treatment include surgery, radioactive iodine ablation, and thyroid stimulating hormone suppression. The National Comprehensive Cancer Network guidelines recommend two tyrosine kinase inhibitors for thyroid cancer patients who are non-responsive to iodine: sorafenib and lenvatinib.

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Background: Our purpose was to assess the accuracy of resting energy expenditure (REE) equations in patients with newly diagnosed stage I-IV non-small cell lung, rectal, colon, renal, or pancreatic cancer.

Methods: In this cross-sectional study, REE was measured using indirect calorimetry and compared with 23 equations. Agreement between measured and predicted REE was assessed via paired t-tests, Bland-Altman analysis, and percent of estimations ≤ 10% of measured values.

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Understanding resting energy expenditure (REE) is important for determining energy requirements; REE might be altered in individuals with cancer. The objective of this study was to characterize determinants of REE in patients with stages II-IV colorectal cancer (CRC). REE was measured via indirect calorimetry in patients with newly diagnosed CRC.

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Background & Aims: Resting energy expenditure (REE) is variable in cancer and might be influenced by changes in tumor burden, systemic inflammation, and body composition. The objective of this study was to assess REE change and the predictors of such in patients with stage III or IV colorectal cancer.

Methods: REE was measured via indirect calorimetry and fat mass and fat-free mass (FFM) were assessed using dual X-ray absorptiometry as part of a unique analysis of two studies.

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Objectives: Patients with advanced pancreatic cancer (APC) have a poor prognosis and experience a large burden of disease-related symptoms. Despite advancements in the treatment of APC, survival is dismal and controlling disease-related symptoms and maintaining quality of life is paramount. We hypothesize that an improvement in disease-related symptoms, and therefore, a clinical benefit, while on chemotherapy is a predictive marker in APC.

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Objectives: This phase II, open-label study was designed to evaluate the response rate to the polo-like kinase 1 (Plk-1) inhibitor BI 2536 in patients with sensitive-relapsed small cell lung cancer (SCLC). Secondary endpoints included progression-free survival (PFS), overall survival (OS), duration of response, and safety.

Materials And Methods: Patients were treated with the recommended phase II dose of 200mg of BI 2536 intravenously every 21days.

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Aim: To quantify the effect of food on the systemic exposure of lapatinib at steady state when administered 1 h before and after meals, and to observe the safety and tolerability of lapatinib under these conditions in patients with advanced solid tumours.

Methods: This was a three-treatment, randomised, three-sequence cross-over study. Lapatinib was administered 1 h after a low- [B] or a high-fat [C] meal and systemic exposure was compared with that obtained following administration 1 h before a low-fat meal [A].

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Purpose: Pharmaceutical development involves substantial financial risk. This risk, rising development costs, and the promotion of continued research and development have been cited as major drivers in the progressive increase in drug prices. Currently, cost-effective analyses are being used to determine the value of treatment.

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Introduction: Endometrial cancer generally presents as early and resectable disease, but about 20% of patients present with either incurable or recurrent/metastatic disease. Patients with good performance status will be treated with hormonal agents, including progestins and tamoxifen, followed by cytotoxic chemotherapy. The options are restricted to hormonal agents for those with multiple comorbidities and older age.

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Background: Involuntary weight loss is a major contributor to mortality and morbidity in patients with advanced cancer. Nutritional intervention with fish oil (FO)-derived eicosapentaenoic acid (EPA) may prevent deterioration of body composition. This study compared intervention with FO with standard of care (SOC; no intervention) with regard to weight, skeletal muscle, and adipose tissue in newly referred patients with nonsmall cell lung cancer from the time of initiation to completion of first-line chemotherapy.

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Background: Palliative chemotherapy is aimed at increasing survival and palliating symptoms. However, the response rate to first-line chemotherapy in patients with nonsmall cell lung cancer (NSCLC) is less than 30%. Experimental studies have shown that supplementation with fish oil (FO) can increase chemotherapy efficacy without negatively affecting nontarget tissue.

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Article Synopsis
  • A 63-year-old man with cirrhosis and hepatocellular carcinoma experienced elevated bilirubin levels after receiving sorafenib as part of a combination trial with chemotherapy drugs.
  • He had one mutant allele of the UGT1A1 gene (UGT1A1*28), which may have contributed to the increased bilirubin levels due to the inhibition of UGT1A1 by sorafenib.
  • The study highlights the need for monitoring bilirubin levels in patients on sorafenib and suggests further research to understand its effects on unconjugated bilirubin in those with Gilbert's syndrome.
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Purpose: The main objectives of this phase I and pharmacokinetic, open-label study were to determine the optimally tolerated regimen (OTR), safety, pharmacokinetics, and clinical activity of lapatinib in combination with letrozole in patients with advanced solid malignancies.

Experimental Design: Patients with advanced breast cancer with immunohistochemically detectable estrogen or progesterone receptors or other cancers were eligible. Doses of lapatinib were escalated in cohorts of three subjects from 1,250 to a maximum of 1,500 mg/d based on dose-limiting toxicities in the first treatment cycle.

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Purpose: This phase I trial (EGF10005) assessed the safety, optimally tolerated regimen (OTR), and pharmacokinetics of lapatinib and capecitabine in combination in patients with advanced solid malignancies.

Patients And Methods: Patients with previously treated, advanced solid malignancies were eligible. Cohorts of at least three patients each received once-daily oral lapatinib (continuous) and capecitabine (twice daily for 14 days every 21 days).

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This phase II study evaluated the antitumor activity of the tetracycline analog COL-3, a potent inhibitor of metalloproteinases (MMPs), particularly MMP-2 and MMP-9, on a continuous oral schedule at a dose of 50 mg/m2 daily in patients with advanced and/or metastatic soft tissue sarcoma (STS). The principal endpoints were the rate of objective tumor regression and the proportion of patients who did not experience disease progression during the first 8 weeks of treatment. Other study objectives included an assessment of pharmacology of COL-3, time to progression (TTP), and overall survival.

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Purpose: To determine the safety, tolerability, and pharmacokinetics and to seek preliminary evidence of anticancer activity of tasidotin (ILX651), a novel dolastatin analogue, when administered as a 30-minute i.v. infusion weekly for 3 weeks every 4 weeks.

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