Evidence suggests that lean body mass (LBM) may be useful to normalize chemotherapy doses. Data from one prospective and one retrospective study were used to determine if the highest doses of oxaliplatin/kg LBM within FOLFOX regimens would be associated with dose-limiting toxicity (DLT) in colon cancer patients. Toxicity over four cycles was graded according to NCI Common Toxicity Criteria V2 o...

BACKGROUND To determine, for each of two dosing schedules, the dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD) of AZD1152, an Aurora B kinase inhibitor, and to evaluate its safety, biologic activity and pharmacokinetics (PK). PATIENTS AND METHODS Patients with advanced solid malignancies were treated with escalating doses (100-650 mg) of AZD1152, administered as a 2-h infusion e...

BACKGROUND Sorafenib induces frequent dose limiting toxicities (DLT) in patients with advanced hepatocellular carcinoma (HCC). Sarcopenia has been associated with poor performance status and shortened survival in cancer patients. PATIENTS AND METHODS The characteristics of Child Pugh A cirrhotic patients with HCC receiving sorafenib in our institution were retrospectively analyzed. Sorafenib ...

An understanding of the regulatory mechanisms that drive Staphylococcus aureus biofilm formation may lead to the development of an effective strategy to control the increasing number of refractory clinical infections it causes. The present study examined the effects of the antimicrobial agent human β‑defensin 3 (hBD‑3) and the antibiotics vancomycin and clindamycin on the expression of the S. a...

The extent to which a drug inhibits a target responsible for a therapeutic effect is a more rational primary endpoint for dose-finding studies of more selective anticancer drugs than the conventional endpoint of dose-limiting toxicity (DLT) used for cytotoxic agents. An adaptive phase I trial design incorporating maximum target inhibition as the primary endpoint was developed to define the opti...

BACKGROUND Epidermal growth factor receptor (EGFR) is a new target for nasopharyngeal carcinoma (NPC) therapy. This prospective phase I study sought to determine the safety and recommended phase II dose of icotinib, a novel highly selective oral EGFR tyrosine kinase inhibitor, in combination with intensity-modulated radiotherapy (IMRT) in patients with NPC. METHODS Eligible patients with NPC ...

OBJECTIVE In Japan, 5-fluorouracil (5-FU) 400 mg/m(2) on Days 1-5, 8-12, 36-40 and 43-46 with cisplatin (CDDP) 40 mg/m(2) on Days 1, 8, 36 and 43 plus concurrent radiotherapy with 2 weeks planned interruption (60 Gy) was standard for the patients with esophageal cancer. This Phase I trial was designed to determine the maximal tolerated dose (MTD) and dose-limiting toxicity (DLT) of 5-FU on Days...

PURPOSE Patients who do not complete one cycle of therapy on Phase I trials for reasons other than dose limiting toxicity (DLT) are considered inevaluable for toxicity and must be replaced. METHODS Individual records from patients enrolled to NCI-sponsored Phase I trials activated between 2000 and 2010 were used. Early discontinuation was defined as the failure to begin cycle 2 for reasons ot...

We discuss the continual reassessment method (CRM) and its extension with practical applications in phase I and I/II cancer clinical trials. The CRM has been proposed as an alternative design of a traditional cohort design and its essential features are the sequential (continual) selection of a dose level for the next patients based on the dose-toxicity relationship and the updating of the rela...

PURPOSE To evaluate the toxicity profile of inhalational doxorubicin in patients with malignant disease in the lung. EXPERIMENTAL DESIGN The OncoMyst Model CDD-2a inhalation device aerosolizes compounds to particles of 2 to 3 mum and prevents exhaled aerosol from escaping into the environment. Deposition efficiency of inhaled Technetium 99m was used to predict deposition of doxorubicin and ca...