A Phase I Dose-Escalation Study Evaluating the Safety Tolerability and Pharmacokinetics of CUDC-427, a Potent, Oral, Monovalent IAP Antagonist, in Patients with Refractory Solid Tumors.

Purpose: To determine the dose-limiting toxicities (DLT), adverse events (AE), pharmacokinetics, and preliminary evidence of antitumor activity of CUDC-427 (formerly GDC-0917), a selective antagonist of inhibitor of apoptosis (IAP) proteins.

Experimental Design: Patients with advanced solid malignancies were treated with escalating doses of CUDC-427 orally on a daily 14-day on/7-day off schedule in 21-day cycles using a modified continuous reassessment method design. Blood samples were assayed to determine the pharmacokinetic properties, pharmacodynamic alterations of cellular IAP levels in peripheral blood mononuclear cells (PBMC), and monocyte chemoattractant protein-1 (MCP-1) levels.

A phase 1B study of dulanermin in combination with modified FOLFOX6 plus bevacizumab in patients with metastatic colorectal cancer.

Objectives: The study objectives were to evaluate the safety, tolerability, and preliminary efficacy of multiple doses of dulanermin in combination with modified FOLFOX6 and bevacizumab in previously untreated patients with locally advanced, recurrent, or metastatic colorectal cancer.

Patients And Methods: A total of 23 patients received dulanermin at dosages of 4.5 or 9 mg/kg/d given on days 1 to 3 of each 14-day cycle along with standard dosing of modified FOLFOX6 plus bevacizumab.

Learning and confirming with preclinical studies: modeling and simulation in the discovery of GDC-0917, an inhibitor of apoptosis proteins antagonist.

The application of modeling and simulation techniques is increasingly common in the preclinical stages of the drug development process. GDC-0917 [(S)-1-((S)-2-cyclohexyl-2-((S)-2-(methylamino)propanamido)acetyl)-N-(2-(oxazol-2-yl)-4-phenylthiazol-5-yl)pyrrolidine-2-carboxamide] is a potent second-generation antagonist of inhibitor of apoptosis (IAP) proteins that is being developed for the treatment of various cancers. GDC-0917 has low to moderate clearance in the mouse (12.

FOLFIRI plus dulanermin (rhApo2L/TRAIL) in a patient with BRAF-mutant metastatic colon cancer.

Colorectal cancer patients with BRAF-mutant tumors have a more aggressive, rapidly progressing disease that is in critical need of novel therapeutic approaches. Indeed, whereas the median overall survival (OS) of colorectal cancer (CRC) patients receiving standard-of-care therapy is approximately two years or more if their tumors express wild-type BRAF and wild-type KRAS, median OS is less than twelve months with tumors expressing V600E-mutant BRAF and wild-type KRAS. Pro-apoptotic receptor agonists are a class of biologic agents under development to induce tumor-specific apoptosis and are being combined with classical chemotherapy or targeted agents in clinical trials.

Phase Ib study of drozitumab combined with first-line mFOLFOX6 plus bevacizumab in patients with metastatic colorectal cancer.

In this multicenter phase Ib study, drozitumab was given in combination with the mFOLFOX6 regimen and bevacizumab in patients with previously untreated, locally advanced recurrent or metastatic colorectal cancer on day 1 of every 14-day cycle. Nine patients were treated at 2 different cohort dose levels of drozitumab. No dose-limiting toxicities occurred at either dose level and the maximum tolerated dose was not reached.

Evaluation of lymphangiogenic factors, vascular endothelial growth factor D and E-cadherin in distinguishing inflammatory from locally advanced breast cancer.

Background: Inflammatory breast cancer (IBC) is an aggressive form of breast cancer that on presentation resembles locally advanced breast cancer (LABC). This study identified molecular features of IBC and LABC to investigate pathogenesis.

Materials And Methods: This study involved 100 IBC cases identified in a national IBC registry and 107 non-IBC LABC cases from the National Cancer Institute's Cooperative Breast Cancer Tissue Resource (CBCTR).

Cardiac toxicity and efficacy of trastuzumab combined with pertuzumab in patients with [corrected] human epidermal growth factor receptor 2-positive metastatic breast cancer.

Purpose: To evaluate safety and efficacy of trastuzumab with pertuzumab in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer who had progressive disease on trastuzumab-based therapy.

Experimental Design: Patients with measurable HER2(+) metastatic breast cancer, < or = 3 trastuzumab-based regimens, and left ventricular ejection fraction (LVEF) > or = 55% received 8 or 6 mg/kg trastuzumab and 840 mg pertuzumab i.v.

Optic neuropathy from metastatic squamous cell carcinoma of the cervix: an unusual CNS presentation.

Background: Central nervous system (CNS) metastases from cervical carcinoma are uncommon events. Leptomeningeal involvement from cervical squamous cell carcinoma has not been extensively described.

Case: A 43-year-old woman with initial diagnosis of stage IB squamous cervical carcinoma at age 30 was treated with hysterectomy and left salpingo-oophorectomy.