Safety, antitumor activity, and pharmacokinetics of dostarlimab, an anti-PD-1, in patients with advanced solid tumors: a dose-escalation phase 1 trial.

Purpose: New immuno-oncology therapies targeting programmed cell death receptor 1 (PD-1) have improved patient outcomes in a broad range of cancers. The objective of this analysis was to evaluate the PK, pharmacodynamics (PDy), and safety of dostarlimab monotherapy in adult patients with previously-treated advanced solid tumors who participated in parts 1 and 2A of the phase 1 GARNET study.

Methods: Part 1 featured a 3 + 3 weight-based dose-escalation study, in which 21 patients received dostarlimab 1, 3, or 10 mg/kg intravenously every 2 weeks.

Multicenter phase II trial (SWOG S1609, cohort 51) of ipilimumab and nivolumab in metastatic or unresectable angiosarcoma: a substudy of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART).

Purpose: Angiosarcoma is a rare aggressive endothelial cell cancer with high mortality. Isolated reports suggest immune checkpoint inhibition efficacy in angiosarcoma, but no prospective studies have been published. We report results for angiosarcoma treated with ipilimumab and nivolumab as a cohort of an ongoing rare cancer study.

First-In-Human Study of Cemiplimab Alone or In Combination with Radiotherapy and/or Low-dose Cyclophosphamide in Patients with Advanced Malignancies.

Purpose: This first-in-human study assessed the safety, tolerability, dose-limiting toxicities (DLT), antitumor activity, and pharmacokinetics of cemiplimab, a monoclonal anti-programmed cell death-1 (PD-1), as monotherapy and in combination with hypofractionated radiotherapy (hfRT) and/or cyclophosphamide (CPA) in patients with advanced solid tumors.

Patients And Methods: Patients were enrolled in 1 of 10 dose escalation cohorts and received cemiplimab 1, 3, or 10 mg/kg every 2 weeks intravenously for up to 48 weeks. Depending on the cohort, patients received hfRT and/or low-dose (200 mg/m) CPA.

Isolated Colonic Metastasis From Esophageal Adenocarcinoma.

Esophageal cancer is an aggressive and highly lethal malignancy that has a high death-to-incidence ratio approaching 0.90. We present a 60-year-old man with a history of Barrett's esophagus, presented with dysphagia.

Management of malignant biliary diseases by the use of peroral and percutaneous cholangioscopy.

Background And Aims: The single-operator digital cholangioscope has allowed visual access to the biliary tree and the ability to perform selective biopsies. This has significantly improved our diagnostic yield in bile-duct disorders. Cholangioscopy requires specialized equipment and expertise.

Endoscopic management of colovaginal fistulas in advanced cancer patients.

Background And Aims: Colovaginal fistula (CVF) in cancer patients can cause significant morbidity. In addition to causing local symptoms and infections, the constant stool leakage contributes to a poor quality of life, psychological distress, and possible social isolation. Patients with CVFs often have advanced disease, poor nutrition, and complex anatomy, making them poor candidates for major surgical interventions.

Correction to: Phase Ib/II study of gemcitabine, nab-paclitaxel, and pembrolizumab in metastatic pancreatic adenocarcinoma.

The authors would like to note an error in Figures 1 and 2 of this paper. The graph in Figure 1 incorrectly reflected the overall survival (OS), when it should have displayed the progression-free survival (PFS). The caption and median PFS values were correct.

Readmission After Pediatric Cardiothoracic Surgery: An Analysis of The Society of Thoracic Surgeons Database.

Background: Hospital readmission after pediatric cardiac surgery is incompletely understood. This study analyzed data from The Society of Thoracic Surgeons Congenital Heart Surgery Database to determine prevalence, to describe patient characteristics, and to evaluate risk factors for readmission.

Methods: Readmission was defined by the "readmission within 30 days after discharge" field.

A New and Safe Mode of Ventilation for Interventional Pulmonary Medicine: The Ease of Nasal Superimposed High Frequency Jet Ventilation.

We use pulmonary interventional procedures for the diagnosis of pulmonary diseases either for benign or malignant lesions. Flexible bronchoscopy with or without radial endobronchial ultrasound, convex-probe endobronchial ultrasound and electromagnetic navigation are procedures performed in centers with experience in diagnostic pulmonary medicine. The method of sedation and ventilation is very important in order to avoid or handle with success complications.

A retrospective matched cohort study evaluating the effects of percutaneous endoscopic gastrostomy feeding tubes on nutritional status and survival in patients with advanced gastroesophageal malignancies undergoing systemic anti-cancer therapy.

Background: Many patients with cancer or other systemic illnesses can experience malnutrition. One way to mitigate malnutrition is by insertion of a percutaneous endoscopic gastrostomy feeding tube (PEG tube). The goal of this retrospective matched cohort study is to evaluate if PEG tube placement improved nutritional status and overall survival (OS) in advanced gastroesophageal (GE) cancer patients who are undergoing anti-neoplastic therapy.

Phase Ib/II study of gemcitabine, nab-paclitaxel, and pembrolizumab in metastatic pancreatic adenocarcinoma.

Background A single center phase Ib/II study of gemcitabine, nab-paclitaxel, and pembrolizumab (GNP) to evaluate the safety and efficacy in metastatic pancreatic adenocarcinoma (PDAC) was conducted (NCT02331251). Methods PDAC patients (pts) with measurable disease, biopsy proven metastasis, adequate laboratory tests, and KPS ≥ 70% received GNP until progression or toxicity. Safety monitoring, RECIST 1.

Safety and activity of IT-139, a ruthenium-based compound, in patients with advanced solid tumours: a first-in-human, open-label, dose-escalation phase I study with expansion cohort.

Objective: This phase I clinical study (NCT01415297) evaluated the safety, tolerability, maximum-tolerated dose (MTD), pharmacokinetics and pharmacodynamics of IT-139 (formerly NKP-1339) monotherapy in patients with advanced solid tumours. IT-139, sodium trans-(tetrachlorobis(1H-indazole)ruthenate(III)), is a novel small molecule that suppresses the stress induction of GRP78 in tumour cells. GRP78 is a key regulator of misfolded protein processing, and its upregulation in tumours is associated with intrinsic and drug-induced resistance.

Phase I dose escalation study of NMS-1286937, an orally available Polo-Like Kinase 1 inhibitor, in patients with advanced or metastatic solid tumors.

Background Pharmacological inhibition of polo-like kinase 1 (PLK1) represents a new approach for the treatment of solid tumors. This study was aimed at determining the first cycle dose-limiting toxicities (DLTs) and related maximum tolerated dose (MTD) of NMS-1286937, a selective ATP-competitive PLK1-specific inhibitor. Secondary objectives included evaluation of its safety and pharmacokinetic (PK) profile in plasma, its antitumor activity, and its ability to modulate intracellular targets in biopsied tissue.

A phase Ib study of pembrolizumab plus chemotherapy in patients with advanced cancer (PembroPlus).

Background: Pembrolizumab (P) is an anti-PD-1 antibody that blocks the interaction between programmed cell death protein 1 (PD-1) on T-cells and PD-L1 and PD-L2 on tumour cells. A phase Ib trial of P plus chemotherapy was undertaken to evaluate the safety and efficacy.

Methods: Patients with advanced, metastatic solid tumours were enrolled onto one of six treatment arms.

A prospective pilot study of genome-wide exome and transcriptome profiling in patients with small cell lung cancer progressing after first-line therapy.

Background: Small cell lung cancer (SCLC) that has progressed after first-line therapy is an aggressive disease with few effective therapeutic strategies. In this prospective study, we employed next-generation sequencing (NGS) to identify therapeutically actionable alterations to guide treatment for advanced SCLC patients.

Methods: Twelve patients with SCLC were enrolled after failing platinum-based chemotherapy.

Reviewing concomitant medications for participants in oncology clinical trials.

Purpose: The importance and key components of clinical medication reviews for participants in oncology clinical trials are described, and drug- drug interactions (DDIs) associated with new oncology drug classes are discussed.

Summary: Use of investigational drugs is a mainstay of adult oncology clinical trials and has led to discovery of new oncology drug classes, including immunotherapy agents and oral targeted therapies, as well as novel chemotherapy delivery methods. As sponsor-supplied DDI information on investigational drugs and drug classes is typically limited and often inconsistent, a clinical medication review to assess the potential for DDIs is recommended for all patients enrolling in oncology clinical trials.

Phase 1b trial of proteasome inhibitor carfilzomib with irinotecan in lung cancer and other irinotecan-sensitive malignancies that have progressed on prior therapy (Onyx IST reference number: CAR-IST-553).

Introduction Proteasome inhibition is an established therapy for many malignancies. Carfilzomib, a novel proteasome inhibitor, was combined with irinotecan to provide a synergistic approach in relapsed, irinotecan-sensitive cancers. Materials and Methods Patients with relapsed irinotecan-sensitive cancers received carfilzomib (Day 1, 2, 8, 9, 15, and 16) at three dose levels (20/27 mg/m2, 20/36 mg/m2 and 20/45 mg/m2/day) in combination with irinotecan (Days 1, 8 and 15) at 125 mg/m2/day.

Activity and safety of brigatinib in ALK-rearranged non-small-cell lung cancer and other malignancies: a single-arm, open-label, phase 1/2 trial.

Background: Anaplastic lymphoma kinase (ALK) gene rearrangements are oncogenic drivers of non-small-cell lung cancer (NSCLC). Brigatinib (AP26113) is an investigational ALK inhibitor with potent preclinical activity against ALK mutants resistant to crizotinib and other ALK inhibitors. We aimed to assess brigatinib in patients with advanced malignancies, particularly ALK-rearranged NSCLC.

The Use of Medical Marijuana in Cancer.

The use of medical marijuana in cancer care presents a dilemma for both patients and physicians. The scientific evidence is evolving, yet much of the known information is still insufficient to adequately inform patients as to risks and benefits. In addition, evidence-based dosing and administration information on medical marijuana is lacking.