First-in-human trial exploring safety, antitumor activity, and pharmacokinetics of Sym013, a recombinant pan-HER antibody mixture, in advanced epithelial malignancies.

Purpose: Sym013 contains six humanized monoclonal antibodies that bind to non-overlapping epitopes on three human epidermal growth factor receptors (HER1-3). Preclinical studies suggested Sym013 strongly suppresses growth of multiple epithelial tumors. This is a first-in-human study exploring safety and efficacy of Sym013 in patients with advanced epithelial malignancies.

Efficacy of Sym004 in Patients With Metastatic Colorectal Cancer With Acquired Resistance to Anti-EGFR Therapy and Molecularly Selected by Circulating Tumor DNA Analyses: A Phase 2 Randomized Clinical Trial.

Importance: Acquired resistance to anti-EGFR therapy (epidermal growth factor receptor) is frequently due to RAS and EGFR extracellular domain (ECD) mutations in metastatic colorectal cancer (mCRC). Some anti-EGFR-refractory patients retain tumor EGFR dependency potentially targetable by agents such as Sym004, which is a mixture of 2 nonoverlapping monoclonal antibodies targeting EGFR.

Objective: To determine if continuous blockade of EGFR by Sym004 has survival benefit.

Erlotinib therapy for central nervous system hemangioblastomatosis associated with von Hippel-Lindau disease: a case report.

There is a need for effective systemic therapy for central nervous system (CNS) hemangioblastomas (HBs). We report a case of erlotinib therapy for CNS HBs in a patient with von Hippel-Lindau disease, in whom the HBs were associated with diffuse leptomeningeal seeding. We provide the first report of paired serum and cerebrospinal fluid (CSF) levels of erlotinib while on standard dosing.

Duration and consistency of historical selection are correlated with adaptive trait evolution in the streamside salamander, Ambystoma barbouri.

A fundamental challenge in evolutionary biology concerns estimating the extent to which ecological trade-offs may impose constraints on adaptive evolution. Novel ecological stressors may limit adaptive evolution of naive lineages that have experienced historically different selective regimes. Regarded as recently derived from a pond-breeding ancestor, streamside salamanders face the novel and strong selection pressure of breeding in streams with fish predators.

Phase I, pharmacokinetic, and biological study of erlotinib in combination with paclitaxel and carboplatin in patients with advanced solid tumors.

Purpose: To assess the feasibility of administering erlotinib, an inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, in combination with paclitaxel and carboplatin, and to identify pharmacokinetic interactions, evaluate downstream effects of EGFR inhibition on surrogate tissues, and seek preliminary evidence for clinical activity.

Experimental Design: Patients with advanced solid malignancies were treated continuously with erlotinib at doses of 100, 125, and 150 mg/d orally along with fixed i.v.

Erlotinib plus gemcitabine in patients with unresectable pancreatic cancer and other solid tumors: phase IB trial.

Purpose: The purpose of this phase IB trial was to evaluate the tolerability, pharmacokinetics and preliminary evidence of antitumor activity of erlotinib plus gemcitabine in patients with pancreatic cancer and other solid tumors.

Patients And Methods: Patients included those with advanced pancreatic adenocarcinoma or other malignancies potentially responsive to gemcitabine. In the escalating phase of the trial, patients were enrolled in sequential cohorts using 100 or 150 mg oral daily dosing of erlotinib.

An interactive computer kiosk module for the treatment of recurrent uncomplicated cystitis in women.

Objective: To validate and implement a computer module for the management of uncomplicated urinary tract infections (UTI).

Participants: Women age 18 to 64 years, with a previous UTI, voiding symptoms, and absence of complicating features (comorbidities, vaginal discharge, back pain, emesis, and fever/chills).

Measurements: The computer module was validated against clinician diagnosis and urine culture.

A phase II, double-masked, randomized, placebo-controlled evaluation of a human monoclonal anti-Cytomegalovirus antibody (MSL-109) in combination with standard therapy versus standard therapy alone in the treatment of AIDS patients with Cytomegalovirus retinitis.

ACTG 266 was designed as a randomized study to evaluate two doses of the human monoclonal antibody directed against CMV gH (MSL-109) versus placebo, each in combination with standard antiviral therapy for the treatment of newly diagnosed Cytomegalovirus (CMV) retinitis in AIDS patients. A total of 82 subjects were enrolled and received either placebo (n = 28), or MSL-109 at 15 mg (n = 26) or 60 mg (n = 28) every 2 weeks until disease progression was diagnosed. The primary endpoint, disease progression, was determined by masked reading of retinal photographs taken every 4 weeks read by a single investigator.