Pembrolizumab Plus mFOLFOX7 or FOLFIRI for Microsatellite Stable/Mismatch Repair-Proficient Metastatic Colorectal Cancer: KEYNOTE-651 Cohorts B and D.

Background: The phase 1b KEYNOTE-651 study evaluated pembrolizumab plus chemotherapy in microsatellite stable or mismatch repair-proficient metastatic colorectal cancer.

Patients And Methods: Patients with microsatellite stable or mismatch repair-proficient metastatic colorectal cancer received pembrolizumab 200 mg every 3 weeks plus 5-fluorouracil, leucovorin, oxaliplatin (previously untreated; cohort B) or 5-fluorouracil, leucovorin, irinotecan (previously treated with fluoropyrimidine plus oxaliplatin; cohort D) every 2 weeks. Primary end point was safety; investigator-assessed objective response rate per RECIST v1.

Zanidatamab, a novel bispecific antibody, for the treatment of locally advanced or metastatic HER2-expressing or HER2-amplified cancers: a phase 1, dose-escalation and expansion study.

Background: HER2-targeted therapies have substantially improved outcomes for patients with HER2-positive breast and gastric or gastro-oesophageal junction cancers. Several other cancers exhibit HER2 expression or amplification, suggesting that HER2-targeted agents can have broader therapeutic impact. Zanidatamab is a humanised, bispecific monoclonal antibody directed against two non-overlapping domains of HER2.

Phase 1/2 study of intratumoral G100 (TLR4 agonist) with or without pembrolizumab in follicular lymphoma.

Intratumoral injection of G100, a toll-like receptor 4 (TLR4) agonist, was shown pre-clinically to stimulate anti-tumor immune responses and tumor regression. This open-label, multicenter, phase 1/2 trial evaluated the safety, tolerability, and preliminary efficacy of intratumoral G100 injections following localized low-dose radiation in patients with follicular lymphoma (ClinicalTrials.gov #NCT02501473).

Safety and Efficacy of Andecaliximab (GS-5745) Plus Gemcitabine and Nab-Paclitaxel in Patients with Advanced Pancreatic Adenocarcinoma: Results from a Phase I Study.

Background: Matrix metalloproteinase 9 (MMP9) expression in the tumor microenvironment is implicated in multiple protumorigenic processes. Andecaliximab (GS-5745), a monoclonal antibody targeting MMP9 with high affinity and selectivity, was evaluated in combination with gemcitabine and nab-paclitaxel in patients with advanced pancreatic adenocarcinoma.

Patients And Methods: This phase I study was completed in two parts: part A was a dose-finding, monotherapy phase that enrolled patients with advanced solid tumors, and part B examined andecaliximab in combination with chemotherapy in specific patient cohorts.

Acalabrutinib monotherapy in patients with relapsed/refractory chronic lymphocytic leukemia: updated phase 2 results.

Therapeutic targeting of Bruton tyrosine kinase (BTK) has dramatically improved survival outcomes for patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Acalabrutinib is an oral, highly selective BTK inhibitor that allows for twice-daily dosing due to its selectivity. In this phase 1b/2 study, 134 patients with relapsed/refractory CLL or SLL (median age, 66 years [range, 42-85 years]; median prior therapies, 2 [range, 1-13]) received acalabrutinib 100 mg twice daily for a median of 41 months (range, 0.

Avelumab monotherapy as first-line or second-line treatment in patients with metastatic renal cell carcinoma: phase Ib results from the JAVELIN Solid Tumor trial.

Background: Antibodies targeting programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1) have shown clinical activity in the treatment of metastatic renal cell carcinoma (mRCC). This phase Ib cohort of the JAVELIN Solid Tumor trial assessed the efficacy and safety of avelumab (anti-PD-L1) monotherapy in patients with mRCC as either first-line (1 L) or second-line (2 L) treatment.

Methods: Patients with mRCC with a clear-cell component who were treatment naive (1 L subgroup) or had disease progression after one prior line of therapy (2 L subgroup) received avelumab 10 mg/kg intravenous infusion every 2 weeks.

Efficacy and Safety of Avelumab for Patients With Recurrent or Refractory Ovarian Cancer: Phase 1b Results From the JAVELIN Solid Tumor Trial.

Importance: Current treatment options for progressive ovarian cancer provide limited benefit, particularly in patients whose disease has become resistant to platinum-based chemotherapy.

Objective: To assess the efficacy and safety of avelumab, an anti-programmed death-ligand 1 agent, in a cohort of patients with previously treated recurrent or refractory ovarian cancer.

Design, Setting, And Participants: In an expansion cohort of a phase 1b, open-label study (JAVELIN Solid Tumor), 125 patients with advanced ovarian cancer who had received chemotherapy including a platinum agent were enrolled between November 6, 2013, and August 27, 2015.

Tucatinib Combined With Ado-Trastuzumab Emtansine in Advanced ERBB2/HER2-Positive Metastatic Breast Cancer: A Phase 1b Clinical Trial.

Importance: Treatment options for patients with disease progression after treatment with trastuzumab, pertuzumab, and ado-trastuzumab emtansine (T-DM1) are limited. Tucatinib is an oral, potent, human epidermal growth factor receptor 2 (HER2)-specific tyrosine kinase inhibitor (TKI) being developed as a novel treatment for ERBB2/HER2-positive breast cancer.

Objective: To determine the maximum tolerated dosage of tucatinib in combination with T-DM1 in the treatment of patients with ERBB2/HER2-positive metastatic breast cancer with and without brain metastases.

Tucatinib with capecitabine and trastuzumab in advanced HER2-positive metastatic breast cancer with and without brain metastases: a non-randomised, open-label, phase 1b study.

Background: Tucatinib is a potent and selective oral HER2 tyrosine kinase inhibitor, with the potential to provide a well tolerated new treatment option for patients whose disease has progressed on currently available therapies. We aimed to determine the recommended phase 2 dose, safety, pharmacokinetics, and preliminary activity of tucatinib in combination with capecitabine or trastuzumab in patients with HER2-positive breast cancer with or without brain metastases.

Methods: In this non-randomised, open-label, phase 1b trial done in five sites in the USA, we recruited patients aged 18 years or older with HER2-positive progressive breast cancer who had been previously treated with trastuzumab, pertuzumab, and trastuzumab emtansine.

Andecaliximab/GS-5745 Alone and Combined with mFOLFOX6 in Advanced Gastric and Gastroesophageal Junction Adenocarcinoma: Results from a Phase I Study.

Matrix metalloproteinase-9 (MMP9) is implicated in protumorigenic processes. Andecaliximab (GS-5745, a monoclonal antibody targeting MMP9) was evaluated as monotherapy and in combination with mFOLFOX6. Three dosages of andecaliximab monotherapy [200, 600, and 1800 mg i.

Mass balance, pharmacokinetics, and metabolism of linsitinib in cancer patients.

Purpose: This study characterized the pharmacokinetics, mass balance, routes and extent of elimination, metabolites, and safety of a single oral dose of (14)C-linsitinib, an IGF-1R/IR inhibitor, in patients with advanced solid tumors. The tolerability of linsitinib after multiple-dose administration was assessed in those patients who wished to continue treatment beyond the single (14)C-linsitinib dose.

Methods: Five patients received a single oral dose of 150 mg (14)C-linsitinib, followed by collection of blood, plasma, urine, and feces for 10 days.

Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia.

Background: Irreversible inhibition of Bruton's tyrosine kinase (BTK) by ibrutinib represents an important therapeutic advance for the treatment of chronic lymphocytic leukemia (CLL). However, ibrutinib also irreversibly inhibits alternative kinase targets, which potentially compromises its therapeutic index. Acalabrutinib (ACP-196) is a more selective, irreversible BTK inhibitor that is specifically designed to improve on the safety and efficacy of first-generation BTK inhibitors.

A phase 1 study of ABT-806 in subjects with advanced solid tumors.

Purpose: ABT-806, a humanized recombinant monoclonal antibody, binds a unique epidermal growth factor receptor (EGFR) epitope exposed in the EGFRde2-7 (EGFRvIII) deletion mutant and other EGFR proteins in the activated state. This phase I study evaluated the safety, pharmacokinetics, and recommended phase two dose (RP2D) of ABT-806 in patients with solid tumors that commonly overexpress activated EGFR or EGFRvlll.

Methods: Patients with advanced solid tumors, including glioblastoma, were eligible.

IGF system in cancer: from bench to clinic.

Insulin-like growth factors (IGFs) are important mediators of growth, development, and survival, and have been implicated in the pathogenesis of malignancies. The IGF system is a complex system comprising two growth factors (IGF-I and IGF-II), cell surface receptors (IGF-IR and IGF-IIR), six specific high-affinity binding proteins (IGFBP-1 to IGFBP-6), IGFBP proteases, and several other IGFBP-interacting molecules that regulate and propagate IGF actions in several tissues. IGFs are produced by almost any cell in the body; circulate in more than 1000-fold higher concentrations than most other peptide hormones, such as insulin, and their action is modulated by several binding proteins.

[A case-control study of extracorporeal versus intracorporeal anastomosis in patients subjected to right laparoscopic hemicolectomy].

Introduction: There is still insufficient scientific evidence on which is the best technique to perform the anastomosis -intracorporeal (IC) or extracorporeal (EC)- in right laparoscopic hemicolectomy. The objective of the present study is to determine whether there are differences to compare in both techniques.

Material And Methods: A study was performed on a prospective patient series subjected to right laparoscopic hemicolectomy in our Hospital.

Phosphodiesterase 4 inhibitors augment levels of glucocorticoid receptor in B cell chronic lymphocytic leukemia but not in normal circulating hematopoietic cells.

Type 4 cyclic AMP (cAMP) phosphodiesterase (PDE4) inhibitors, a class of compounds in clinical development that activate cAMP-mediated signaling by inhibiting cAMP catabolism, offer a feasible means by which to potentiate glucocorticoid-mediated apoptosis in lymphoid malignancies such as B-cell chronic lymphocytic leukemia (B-CLL). In this study, we show that PDE4 inhibitors up-regulate glucocorticoid receptor (GRalpha) transcript levels in B-CLL cells but not T-CLL cells or Sezary cells or normal circulating T cells, B cells, monocytes, or neutrophils. Because GRalpha transcript half-life does not vary in CLL cells treated with the prototypic PDE4 inhibitor rolipram, the 4-fold increase in GRalpha mRNA levels observed within 4 h of rolipram treatment seems to result from an increase in GRalpha transcription.

Aerosolized ribavirin-induced reversible hepatotoxicity in a hematopoietic stem cell transplant recipient with Hodgkin lymphoma.

We describe a case of acute hepatic toxicity associated with aerosolized ribavirin in a bone marrow transplant recipient with documented respiratory syncytial virus infection. The temporal relationship with drug administration and the liver biopsy results suggested drug-induced hepatic injury. As the use of aerosolized ribavirin to treat respiratory syncytial virus infections continues, it is imperative that careful attention be paid to possible adverse effects of therapy in the high-risk population of immunosuppressed patients.

[Determining exposure history in occupational epidemiology].

In epidemiology, it is necessary that exposure indicators have good validity in order to obtain valid results when measuring the risks associated with occupational exposure to environmental noxious agents. However, ensuring the validity of past exposure data is no easy task. Because there are no environmental hygiene measures or representative levels of bioindicators signaling past exposure, self-reports have been used as a source of indirect exposure data.

Workplace carcinogen and pesticide exposures in Costa Rica.

The CAREX data system converts national workforce volumes and proportions of workers exposed to workplace carcinogens into numbers of exposed in 55 industrial categories. CAREX was adapted for Costa Rica for 27 carcinogens and seven groups of pesticides. Widespread workplace carcinogens in the 1.