Phase I trial of the oral PARP inhibitor olaparib in combination with paclitaxel for first- or second-line treatment of patients with metastatic triple-negative breast cancer.

Introduction: This Phase I study evaluated the safety, tolerability and efficacy of olaparib, a potent oral poly(ADPribose) polymerase (PARP) inhibitor, in combination with paclitaxel in patients with metastatic triple-negative breast cancer (mTNBC).

Methods: Eligible patients who had received ≤1 prior cytotoxic regimen for mTNBC were treated with olaparib 200 mg bid continuously plus weekly paclitaxel 90 mg/m2 for three weeks per four-week cycle. Dose modifications in a large proportion of patients due to neutropenia resulted in enrollment of a second cohort of patients who, if they experienced grade ≥2 neutropenia in cycle 1, received granulocyte-colony stimulating factor, which was continued prophylactically in subsequent cycles.

Molecular predictors of outcome with gefitinib and docetaxel in previously treated non-small-cell lung cancer: data from the randomized phase III INTEREST trial.

PURPOSE In the phase III INTEREST trial, 1,466 pretreated patients with advanced non-small cell lung cancer (NSCLC) were randomly assigned to receive gefitinib or docetaxel. As a preplanned analysis, we prospectively analyzed available tumor biopsies to investigate the relationship between biomarkers and clinical outcomes. METHODS Biomarkers included epidermal growth factor receptor (EGFR) copy number by fluorescent in situ hybridization (374 assessable samples), EGFR protein expression by immunohistochemistry (n = 380), and EGFR (n = 297) and KRAS (n = 275) mutations.

Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma.

Background: Previous, uncontrolled studies have suggested that first-line treatment with gefitinib would be efficacious in selected patients with non-small-cell lung cancer.

Methods: In this phase 3, open-label study, we randomly assigned previously untreated patients in East Asia who had advanced pulmonary adenocarcinoma and who were nonsmokers or former light smokers to receive gefitinib (250 mg per day) (609 patients) or carboplatin (at a dose calculated to produce an area under the curve of 5 or 6 mg per milliliter per minute) plus paclitaxel (200 mg per square meter of body-surface area) (608 patients). The primary end point was progression-free survival.

Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial.

Background: Two phase II trials in patients with previously-treated advanced non-small-cell lung cancer suggested that gefitinib was efficacious and less toxic than was chemotherapy. We compared gefitinib with docetaxel in patients with locally advanced or metastatic non-small-cell lung cancer who had been pretreated with platinum-based chemotherapy.

Methods: We undertook an open-label phase III study with recruitment between March 1, 2004, and Feb 17, 2006, at 149 centres in 24 countries.

A Randomized Study of Electronic Diary versus Paper and Pencil Collection of Patient-Reported Outcomes in Patients with Non-Small Cell Lung Cancer.

Background: Hand-held electronic devices may provide a simple reproducible means by which quality of life (QOL) may be documented in patients with cancer. However, the QOL scales that are routinely used were originally validated when used with paper and pencil data collection. Patient-reported outcomes acquired using hand-held electronic devices (electronic patient-reported outcomes [e-PRO]) may not be the same as those acquired using paper and pencil, so validation of this method of data collection is needed.

Tilt and reading speed.

Purpose: To measure the effect of head tilt on reading rate and to determine whether a difference existed between the body or the text being tilted.

Methods: The Wilkins Rate of Reading Test was used to measure rate of reading in a population of normal readers. In the first part of the study, rate of reading with a head tilt of 15 degrees and 30 degrees was measured; in the second part of the study, rate of reading with a body tilt of 45 degrees and 90 degrees or a text tilt of 45 degrees and 90 degrees was measured.

Effect of oral linezolid on the pressor response to intravenous tyramine.

Aims: To investigate the effect of monoamine oxidase A inhibition from a single oral dose of linezolid on the pressor response to intravenous (i.v.) tyramine, using positive and negative controls to validate the methodology.