A phase-1 trial of linsitinib (OSI-906) in combination with bortezomib and dexamethasone for the treatment of relapsed/refractory multiple myeloma.

We report results of a phase-1 study evaluating the safety and anti-cancer activity of the small molecule insulin-like growth factor-1 receptor (IGF-1R) inhibitor, linsitinib combined with bortezomib, and dexamethasone in relapsed/refractory multiple myeloma. Nineteen patients were enrolled across four dose-escalation cohorts (75-150 mg bid). The maximum tolerated dose of linsitinib was 125 mg.

Patient-reported acute fatigue in elderly breast cancer patients treated with and without regional nodal radiation.

Purpose: Although regional nodal irradiation (RNI) improves outcomes in breast cancer (BC) patients, it is associated with increased toxicity. Therefore, controversy still exists surrounding its indications. The purpose of this study was to evaluate and compare patient-reported acute fatigue in elderly BC patients with and without regional nodal radiation (RNI).

An open-label, pharmacokinetic study of lenalidomide and dexamethasone therapy in previously untreated multiple myeloma (MM) patients with various degrees of renal impairment - validation of official dosing guidelines.

Lenalidomide is a backbone agent in the treatment of multiple myeloma, but dose adjustment is required for those with renal impairment (RI). We evaluated the pharmacokinetics (PK) and safety of lenalidomide and dexamethasone as frontline pre-transplant induction, with doses adjusted at start of each cycle based on creatinine clearance, as per the official dosing guidelines. After 4 cycles, PK studies showed that patients with moderate RI (30 ≤ CrCl < 60 mL/min) receiving 10 mg dosing may be under-dosed and those with severe RI (CrCl <30ml/min) appeared appropriately dosed initially, but sustained significant decreases in maximum serum concentration (Cmax) after repeated dosing, due to rapid clinical improvement and enhanced drug clearance.

A phase 2 study of lenalidomide and dexamethasone in previously untreated patients with chronic lymphocytic leukemia (CLL).

Lenalidomide has anti-tumor activity in CLL but can be complicated by tumor lysis syndrome (TLS) and tumor flare (TF). In our previous study using low-dose lenalidomide in treatment-naive CLL, TLS was averted but TF remained frequent and complete responses (CR) were rare, despite treatment to progression. The addition of dexamethasone may mitigate TF and enable lenalidomide dose escalation, achieving durable response without long-term use.

Ultracentral Tumors Treated With Stereotactic Body Radiotherapy: Single-Institution Experience.

Introduction: Patients with ultracentral lung tumors, whose planning target volume directly contacts or overlaps the proximal bronchial tree, trachea, esophagus, pulmonary vein, or pulmonary artery, may be at higher risk of toxicity when treated with stereotactic body radiotherapy (SBRT). We reviewed the outcomes and toxicities of ultracentral lung tumors and compared the results with central lung tumors.

Patients And Methods: A review of our institutional prospective database of patients treated with lung SBRT from January 2006 to December 2015 was conducted.

Low Incidence of Esophageal Toxicity After Lung Stereotactic Body Radiation Therapy: Are Current Esophageal Dose Constraints Too Conservative?

Purpose: To explore and quantify the relationship between esophageal dose and toxicity in the setting of lung stereotactic body radiation therapy (SBRT).

Methods And Materials: This analysis was conducted on the basis of a prospective study of patients treated with SBRT at our institution from October 2004 to December 2015. Most patients were treated with 54 Gy/3 fractions, 48 Gy/4 fractions alternate days, or 60 Gy/8 fractions daily.

Distribution and Impact of Comorbidities on Survival and Leukemic Transformation in Myeloproliferative Neoplasm-Associated Myelofibrosis: A Retrospective Cohort Study.

Background: We sought to describe the distribution and impact of comorbidities on outcomes in patients with myelofibrosis, a disease characterized by aberrant bone marrow function with eventual fibrosis. Comorbidities were scored using the Adult Comorbidity Evaluation-27 (ACE-27) and the Hematopoietic Cell Transplant Comorbidity Index (HCT-CI), in which a score ≥ 3 indicates severe comorbidities.

Patients And Methods: We conducted a retrospective study of 306 patients with a confirmed diagnosis of myelofibrosis.

Clinical impact of mutation fraction in epidermal growth factor receptor mutation positive NSCLC patients.

Background: We examined clinical outcomes in a population-based cohort of EGFR mutant advanced NSCLC patients, exploring the potential role of factors including tumour EGFR mutation fraction and cellularity in predicting outcomes.

Methods: A cohort of patients with EGFR mutant advanced NSCLC was identified (N =2 93); clinical outcomes, pathologic and treatment details were collected. Tumour response was determined from radiology and clinical notes.

Effect of Red Blood Cell Transfusion Dependence on the Natural History of Myeloproliferative Neoplasm-Associated Myelofibrosis.

Background: There are 2 widely used criteria for red blood cell (RBC) transfusion dependence in persons with myeloproliferative neoplasm (MPN)-associated myelofibrosis: (1) the International Working Group-Myelofibrosis Research and Therapy (IWG-MRT) criteria (receipt of 2 U RBC in the preceding month); and (2) the Rand-Delphi definition (2 U RBC per month averaged over 3 months). We studied effect of these criteria on survival and risk of leukemic transformation in 259 subjects with MPN-associated myelofibrosis.

Patients And Methods: On the basis of hemoglobin (Hb) and transfusion history, subjects were assigned to 1 of the 4 cohorts: (1) Hb ≥ 100 g/L (n = 136; 52%) and no RBC transfusions in the preceding 4 months; (2) Hb < 100 g/L, and no RBC transfusions in the preceding 4 months (n = 56; 22%); (3) subjects who met IWG-MRT criteria, but not the Rand-Delphi criteria for RBC transfusion dependence (n = 34; 13%); and (4) subjects who met the Rand-Delphi criteria for RBC transfusion dependence (n = 33; 13%).

Real-world chemotherapy treatment patterns in metastatic non-small cell lung cancer: Are patients undertreated?

Background: New therapies for metastatic non-small cell lung cancer (NSCLC) have improved survival in clinical trials. However, only a minority of patients receive systemic therapy. This article reports treatment patterns and outcomes for a population of Canadian patients with metastatic NSCLC (Ontario).

Treatment of muscle-invasive bladder cancer in Canada: A survey of genitourinary medical oncologists and urologists.

Introduction: Uptake of neoadjuvant chemotherapy (NC) for muscle invasive bladder cancer (MIBC) has been low despite evidence of a survival benefit. The primary aim of this study was to better understand why the rates are low and determine what factors specifically influence the decision to recommend NC for MIBC.

Methods: A 31-question survey was emailed between 2009 and 2011 to medical oncologists belonging to the Canadian Association of Genitourinary Medical Oncologists (CAGMO); and to urologists belonging to the Canadian Urologic Oncology Group (CUOG).

Single-agent lenalidomide in the treatment of previously untreated chronic lymphocytic leukemia.

Purpose: Lenalidomide is an oral immunomodulatory drug with multiple effects on the immune system and tumor cell microenvironment leading to inhibition of malignant cell growth. Based on encouraging reports of lenalidomide in relapsed and refractory chronic lymphocytic leukemia (CLL), we investigated the first-line use of single-agent lenalidomide in CLL.

Patients And Methods: Using a starting dose of lenalidomide 10 mg/d for 21 days of a 28-day cycle and weekly 5-mg dose escalations to a target of 25 mg, we encountered severe toxicities (tumor lysis, fatal sepsis) in the first two patients enrolled.

Prospective comparison of breast pain in patients participating in a randomized trial of breast-conserving surgery and tamoxifen with or without radiotherapy.

Purpose: To determine whether breast pain affects quality of life (QOL) after breast-conserving surgery and tamoxifen (TAM) with or without adjuvant breast radiotherapy (RT).

Methods And Materials: A randomized clinical trial was carried out at the Princess Margaret Hospital between 1992 and 2000 to evaluate the need for breast RT in addition to TAM in women >or=50 years treated with breast-conserving surgery for T1-T2N0 breast cancer. A companion study to assess breast pain was carried out during the last 2 years of the randomized clinical trial.

Concurrent cyclophosphamide, methotrexate, and 5-fluorouracil chemotherapy and radiotherapy for breast carcinoma: a well tolerated adjuvant regimen.

Background: The current study was conducted to assess the toxicity of concurrent adjuvant cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) chemotherapy and radiotherapy (RT) for early breast carcinoma.

Methods: In the current study, the authors reviewed the records of 680 consecutive breast carcinoma patients who received adjuvant CMF at the Princess Margaret Hospital between 1980-1990. Surgery was comprised of mastectomy in 64% of patients, breast conservation in 35% of patients, and was unknown in 1% of patients.