Barriers to cancer clinical trial accrual can be prospectively identified and addressed in the development and conduct of future studies, which may potentially lead to more robust clinical trials enrollment. Investigation of patient perceptions regarding the clinical trials process and the role of third party-payers is warranted.

In this unselected population, gefitinib did not improve survival. Decreased survival was a result of tumor progression and not gefitinib toxicity.

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Gefitinib is an active agent in advanced stage BAC. Several subsets demonstrate significantly improved clinical outcomes.

Paclitaxel (Taxol), a promoter of microtubule polymerization and a radiosensitizing agent, is one of the more active anticancer drugs in the current treatment of solid tumors. In this study, we show that paclitaxel possesses an antiangiogenic property associated with a down-regulation of vascular endothelial growth factor (VEGF) in a highly-vascularized transgenic murine breast cancer (Met-1). Paclitaxel, at non-cytotoxic doses of 0, 3 and 6 mg/kg/day, was administered intraperitoneally for 5 days to nude mice bearing the Met-1 breast tumor. Extent of intratumoral angiogenesis, as indicated by microvessel tortuosity and microvessel density, was significantly reduced by paclitaxel in a dose-dependent manner. Paclitaxel also suppressed expression of VEGF in the Met-1 cells transplanted in nude mice or maintained in cell culture. These results indicate that antiangiogenesis associated with a down-regulation of VEGF is an additional mode of action of paclitaxel.

Using ''one-bead one-compound'' combinatorial chemistry technology, we generated random peptide libraries containing millions of 90 Mm TentaGel beads, each with its own unique amino acid sequence. A cyclic random 8-mer library was screened with CAOV-3 (a human ovarian adenocarcinoma cell line) and beads with a unique ligand that bind to the cell surface receptors were coated by one or more layers of cells. These positive beads were isolated, stripped, and microsequenced. Several peptide motifs were identified from these screenings, some of which were novel and unique, e.g., cDGX 4 GX 6 X 7 c. Structure-activity relationship studies of this peptide revealed that the L-aspartate residue at position 2, the two glycines at positions 3 and 5, and the two Dcysteines at the amino and COOH terminus are critical for activity. In addition, a hydrophobic residue was preferred at position X 4 , whereas amino acids at positions X 6 and X 7 were more variable. Binding of this peptide to a number of different cancer cell lines and normal cells was also determined and we observed that peptides with this motif bound preferentially to three other human ovarian cancer cell lines (ES-2, SKOV-3, and OVCAR-3) as well as a human glioblastoma cancer cell line (A172). Structural analysis of the peptides using high-resolution nuclear magnetic resonance spectroscopy revealed strong conformational similarity among all peptides with cX 1 GX 4 GX 6 X 7 c motif. Blocking study with a panel of anti-integrin antibodies strongly suggests A3 integrin present on these ovarian adenocarcinoma cells is the target receptor for this peptide. [Mol Cancer Ther 2005;4(5):806 -13]

PurposeTo investigate the association between dose to various anatomical structures and dysphagia among patients with head and neck cancer treated by definitive intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy.Methods and materialsThirty-nine patients with squamous cancer of the head and neck were treated by definitive concurrent chemotherapy and IMRT to a median dose of 70 Gy (range, 68 to 72). In each patient, a gastrostomy tube (GT) was prophylacticly placed prior to starting treatment. Prolonged GT dependence was defined as exceeding the median GT duration of 192 days. Dysphagia was scored using standardized quality-of-life instruments. Dose-volume histogram (DVH) data incorporating the superior/middle pharyngeal constrictors (SMPC), inferior pharyngeal constrictor (IPC), cricoid pharyngeal inlet (CPI), and cervical esophagus (CE) were analyzed in relation to prolonged GT dependence, dysphagia, and weight loss.ResultsAt 3 months and 6 months after treatment, 87% and 44% of patients, respectively, were GT dependent. Spearman's ρ analysis identified statistical correlations (p < 0.05) between prolonged GT dependence or high grade dysphagia with IPC V65, IPC V60, IPC Dmean, and CPI Dmax. Logistic regression model showed that IPC V65 > 30%, IPC V60 > 60%, IPC Dmean > 60 Gy, and CPI Dmax > 62 Gy predicted for greater than 50% probability of prolonged GT dependence.ConclusionOur analysis suggests that adhering to the following parameters may decrease the risk of prolonged GT dependence and dysphagia: IPC V65 < 15%, IPC V60 < 40%, IPC Dmean < 55 Gy, and CPI Dmax < 60 Gy.