Racialized Economic Segregation and Treatment and Outcomes of Small Cell Lung Cancer.

Background: Little is known about the role of residential segregation in the treatment and outcomes of small cell lung cancer (SCLC), a highly recalcitrant disease, among non-Hispanic White (NHW) and non-Hispanic Black (NHB) patients.

Methods: We used the Surveillance, Epidemiology, and End Results database to identify men and women diagnosed with SCLC from January 2007 to December 2015 (n = 38,393). An Index of Concentration at the Extremes was computed to measure county-level racialized economic segregation and categorized into Quartile 1 (most privileged: highest concentration of high-income NHW residents) through Quartile 4 (least privileged: highest concentration of low-income NHB residents).

Prevalence of Women in Medicine Programs at University-Based Internal Medicine Residency Programs.

Objective: Women physicians face various forms of inequities during their training process that inhibit them from reaching their full potential. As a response, several academic institutions have established women in medicine (WIM) programs as a support system. Our objective was to investigate the prevalence of WIM programs at university-based Internal Medicine residency programs as of December 2021.

Investing in Women Trainees: Building a Women in Medicine Group at an Academic Institution.

Given the importance of proactively supporting women trainees in medicine to address gender inequities, we draw on the experience of a well-established professional development initiative to provide a framework for other institutions seeking to create similar trainee-focused programs.

Phase 1b trial of anti-VEGF/PDGFR vorolanib combined with immune checkpoint inhibitors in patients with advanced solid tumors.

Purpose: Vorolanib is a multi-target tyrosine kinase inhibitor with anti-angiogenic properties. This study aimed to evaluate the tolerability, safety and efficacy of vorolanib when added to checkpoint inhibitors (CPIs) in patients with advanced solid tumors.

Methods: We conducted a phase 1b study of vorolanib (300 or 400 mg orally once daily) plus pembrolizumab or nivolumab using a standard 3 + 3 design to determine the dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D).

Phase I Study of Accelerated Hypofractionated Proton Therapy and Chemotherapy for Locally Advanced Non-Small Cell Lung Cancer.

Purpose: Our purpose was to evaluate the maximum tolerated dose of hypofractionated proton beam radiation therapy with concurrent weekly carboplatin/paclitaxel in patients with stage II-III non-small cell lung cancer.

Methods And Materials: A phase I trial was designed using the time-to-event continuous reassessment method. Maximum tolerated dose was defined as the dose associated with a 20% probability of Common Terminology Criteria for Adverse Events protocol-specified serious adverse events (SAEs).

A phase II study of everolimus in patients with advanced solid malignancies with or mutations.

Background: Activation of the mTOR pathway has been implicated in the development of several malignancies and alterations in and , can lead to the dysregulation of this pathway. Furthermore, mutations in and are known to confer sensitivity to everolimus-an mTOR inhibitor. Based on these data, a single-arm, open label, single-institution phase II basket study was designed to assess the activity of everolimus in patients with solid malignancies whose tumors harbored mutations in , or .

Phase I Study of Docetaxel and Temsirolimus in Refractory Solid Tumors.

Introduction: The mammalian target of rapamycin (mTOR) is a downstream mediator in the phosphatidylinositol 3-kinase/Akt signaling pathway, and plays a central role in cell proliferation, growth, differentiation, migration, and survival. Temsirolimus (CCI-779), a selective inhibitor of the mTOR, is an ester analog of rapamycin (sirolimus) with improved aqueous solubility and pharmacokinetic (PK) properties. Preclinical studies have confirmed additive and synergistic antitumor activity in cancer cell lines (breast, prostate cancer) with combinations of taxanes and mTOR inhibitors.

Phase 1 study combining alisertib with nab-paclitaxel in patients with advanced solid malignancies.

Aim: Aurora kinase A (AURKA) is a pleiotropic serine/threonine kinase that orchestrates mitotic progression. Paclitaxel stabilises microtubules and disrupts mitotic spindle assembly. The combination of AURKA inhibitor (alisertib) plus paclitaxel may be synergistic in rapidly proliferative cancers.

Phase II Trial of Carfilzomib Plus Irinotecan in Patients With Small-cell Lung Cancer Who Have Progressed on Prior Platinum-based Chemotherapy.

Introduction: The purpose of this study was to evaluate the efficacy and tolerability of carfilzomib plus irinotecan (C/I) in patients with relapsed small-cell lung cancer (SCLC).

Patients And Methods: Patients with SCLC who progressed after 1 platinum-containing regimen for recurrent or metastatic disease were eligible. Patients were stratified as: sensitive (SS) (progressive disease > 90 days after chemotherapy) or refractory (RS) (progressive disease 30 to 90 days after chemotherapy) and received up to 6 cycles of C/I; imaging was performed every 2 cycles.

Effect of Erlotinib Plus Bevacizumab vs Erlotinib Alone on Progression-Free Survival in Patients With Advanced EGFR-Mutant Non-Small Cell Lung Cancer: A Phase 2 Randomized Clinical Trial.

Importance: Erlotinib is a standard first-line therapy for patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Median progression-free survival (PFS) with erlotinib is approximately 10 months.

Objective: To determine whether adding bevacizumab to erlotinib treatment results in superior progression-free survival compared with erlotinib alone.

Randomized Phase II Trial of Seribantumab in Combination with Erlotinib in Patients with EGFR Wild-Type Non-Small Cell Lung Cancer.

Background: Seribantumab (MM-121) is a fully human IgG2 monoclonal antibody that binds to human epidermal growth factor receptor 3 () to block heregulin ()-mediated signaling and induce receptor downregulation. This open-label, randomized phase 1/2 study evaluated safety and efficacy of seribantumab plus erlotinib in advanced non-small cell lung cancer (NSCLC). Here, we report the activity of seribantumab plus erlotinib, versus erlotinib alone, in patients with wild-type tumors and describe the potential predictive power of HRG.

Phase II study of olaratumab with paclitaxel/carboplatin (P/C) or P/C alone in previously untreated advanced NSCLC.

Background: In non-small cell lung cancer (NSCLC), platelet-derived growth factor receptor (PDGFR) mediates angiogenesis, tissue invasion, and tumor interstitial pressure. Olaratumab (IMC-3G3) is a fully human anti-PDGFRα monoclonal antibody. This Phase II study assessed safety and efficacy of olaratumab+paclitaxel/carboplatin (P/C) versus P/C alone for previously untreated advanced NSCLC.

Phase III Randomized, Placebo-Controlled, Double-Blind Trial of Celecoxib in Addition to Standard Chemotherapy for Advanced Non-Small-Cell Lung Cancer With Cyclooxygenase-2 Overexpression: CALGB 30801 (Alliance).

Purpose Tumor overexpression of cyclooxygenase-2 (COX-2) has been associated with worse outcome in non-small-cell lung cancer (NSCLC). In Cancer and Leukemia Group B (CALGB) 30203, we found that the selective COX-2 inhibitor celecoxib in addition to chemotherapy in advanced NSCLC improved progression-free and overall survival in patients with moderate to high COX-2 expression by immunohistochemistry (IHC). CALGB 30801 (Alliance) was designed to prospectively confirm that finding.

Pulsatile Erlotinib in EGFR-Positive Non-Small-Cell Lung Cancer Patients With Leptomeningeal and Brain Metastases: Review of the Literature.

Patients with epidermal growth factor receptor (EGFR)-positive (EGFR) non-small-cell lung cancer (NSCLC) show improved response rates when treated with tyrosine kinase inhibitors (TKIs) such as erlotinib. However, standard daily dosing of erlotinib often does not reach therapeutic concentrations within the cerebrospinal fluid (CSF), resulting in progression of central nervous system (CNS) disease. Intermittent, high-dose administration of erlotinib reaches therapeutic concentrations within the CSF and is well tolerated in patients.

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.

Maintenance Sunitinib following Initial Platinum-Based Combination Chemotherapy in Advanced-Stage IIIB/IV Non-Small Cell Lung Cancer: A Randomized, Double-Blind, Placebo-Controlled Phase III Study-CALGB 30607 (Alliance).

Introduction: The aim of this study was to evaluate efficacy of maintenance sunitinib after first-line chemotherapy for stage IIIB/IV NSCLC.

Methods: Cancer and Leukemia Group B 30607 trial was a randomized, double-blind, placebo-controlled, phase III study that enrolled patients without progression after four cycles of first-line platinum-based doublet chemotherapy with or without bevacizumab. Bevacizumab was allowed only during the four cycles of chemotherapy.

Adjuvant Chemotherapy for Patients with T2N0M0 NSCLC.

Background: Adjuvant chemotherapy improves survival in patients with completely resected stage II and III NSCLC. However, its role in patients with stage IB NSCLC disease remains unclear. We evaluated the role of adjuvant chemotherapy in a large data set of patients with completely resected T2N0M0 NSCLC.

Delayed nausea and vomiting from carboplatin doublet chemotherapy.

Background: Delayed nausea and vomiting following administration of carboplatin containing chemotherapy regimen remains a clinically significant problem for patients with cancer despite administration of standard antiemetic prophylaxis comprising of a 5-HT3 antagonist and dexamethasone. We performed a prospective study to define the incidence and risk factors for delayed chemotherapy-induced nausea and vomiting (CINV).

Methods: Previously untreated patients with newly diagnosed cancer scheduled to receive carboplatin containing chemotherapy (AUC 5 or above), but no prophylactic aprepitant were enrolled in the study.

A Phase I Trial of Temsirolimus and Pemetrexed in Patients with Advanced Non-Small Cell Lung Cancer.

Background: Pemetrexed is an antifolate chemotherapeutic agent approved for use in non-small cell lung cancer (NSCLC). The mammalian target of rapamycin (mTOR) pathway is implicated in lung cancer development and inhibited by temsirolimus.

Methods: We performed a phase I study evaluating the combination of pemetrexed and temsirolimus in advanced non-squamous NSCLC.

Chemotherapy With or Without Maintenance Sunitinib for Untreated Extensive-Stage Small-Cell Lung Cancer: A Randomized, Double-Blind, Placebo-Controlled Phase II Study-CALGB 30504 (Alliance).

Purpose: To evaluate the efficacy of maintenance sunitinib after chemotherapy for small-cell lung cancer (SCLC).

Patients And Methods: The Cancer and Leukemia Group B 30504 trial was a randomized, placebo-controlled, phase II study that enrolled patients before chemotherapy (cisplatin 80 mg/m(2) or carboplatin area under the curve of 5 on day 1 plus etoposide 100 mg/m(2) per day on days 1 to 3 every 21 days for four to six cycles). Patients without progression were randomly assigned 1:1 to placebo or sunitinib 37.

Postoperative radiotherapy for pathologic N2 non-small-cell lung cancer treated with adjuvant chemotherapy: a review of the National Cancer Data Base.

Purpose: To investigate the impact of modern postoperative radiotherapy (PORT) on overall survival (OS) for patients with N2 non-small-cell lung cancer (NSCLC) treated nationally with surgery and adjuvant chemotherapy.

Patients And Methods: Patients with pathologic N2 NSCLC who underwent complete resection and adjuvant chemotherapy from 2006 to 2010 were identified from the National Cancer Data Base and stratified by use of PORT (≥ 45 Gy). A total of 4,483 patients were identified (PORT, n = 1,850; no PORT, n = 2,633).

Clinical next-generation sequencing in patients with non-small cell lung cancer.

Background: A clinical assay was implemented to perform next-generation sequencing (NGS) of genes commonly mutated in multiple cancer types. This report describes the feasibility and diagnostic yield of this assay in 381 consecutive patients with non-small cell lung cancer (NSCLC).

Methods: Clinical targeted sequencing of 23 genes was performed with DNA from formalin-fixed, paraffin-embedded (FFPE) tumor tissue.

A phase I study of pegylated liposomal doxorubicin and temsirolimus in patients with refractory solid malignancies.

This study aimed to determine the maximum-tolerated dose and dose-limiting toxicities of pegylated liposomal doxorubicin (PLD) in combination with temsirolimus (T) in patients with refractory solid tumors. Using a standard "3+3" dose escalation design, 23 patients were enrolled in three dosing cohorts in this phase I study. The starting dose level was PLD at 30 mg/m(2) every 4 weeks and T at 20 mg weekly.

A phase II study of AT-101 (Gossypol) in chemotherapy-sensitive recurrent extensive-stage small cell lung cancer.

Background: AT-101 is an oral inhibitor of the antiapoptotic Bcl proteins (Bcl-2, Bcl-XL, Bcl-W, and Mcl-1) and an inducer of the pro-apoptotic proteins noxa and puma. We studied the efficacy of AT-101 in patients with recurrent chemosensitive extensive-stage small cell lung cancer (SCLC).

Methods: Patients with recurrent "sensitive" SCLC (defined as no progression during and no disease recurrence <2 months after completion of first-line platinum-based chemotherapy) were eligible.

An open-label, multicenter, three-stage, phase II study of s-1 in combination with cisplatin as first-line therapy for patients with advanced non-small cell lung cancer.

Introduction: S-1 is a rationally designed oral agent that combines the 5-fluorouracil prodrug tegafur with gimeracil and oteracil, which inhibit 5-fluorouracil degradation by dihydropyrimidine dehydronase and phosphorylation within the gastrointestinal tract, respectively, to increase antineoplastic activity while reducing gastrointestinal toxicity. We investigated the activity and toxicity of S-1 in combination with cisplatin in patients with unresectable non-small cell lung cancer (NSCLC).

Methods: Cisplatin, 75 mg/m, was administered intravenously on day 1, with S-1, 25 mg/m PO two times a day, days 1 to 14, every 21 days for a maximum of six cycles.