Correlation of enzyme-inducing anticonvulsant use with outcome of patients with glioblastoma.

Background: Clinical trials involving patients with glioblastoma (GBM) distinguish cohorts who are treated with enzyme-inducing anticonvulsants (EIAC). Such anticonvulsants induce hepatic P450 microsomal enzymes, which accelerate the metabolism of certain chemotherapy and molecular targeted agents. However, the resultant effect of such induction on patient outcome has received limited study.

Predictors of survival from urachal cancer: a Mayo Clinic study of 49 cases.

Background: Outcome results of a long-term analysis of urachal cancer using a new staging system are presented.

Methods: The authors analyzed clinical outcomes from 49 patients with the diagnosis of urachal cancer who were seen at the Mayo Clinic, Rochester, Minnesota from 1950 to 2003. The TNM staging system was used to predict outcome after surgical resection.

A limited sample model to predict area under the drug concentration curve for 17-(allylamino)-17-demethoxygeldanamycin and its active metabolite 17-(amino)-17-demethoxygeldanomycin.

Purpose: The Hsp90-directed anticancer agent 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) is currently undergoing phase I and phase II clinical investigation. Our goal was to develop a simple limited sampling model (LSM) for AUC of 17-AAG and its active metabolite, 17-(amino)-17-demethoxygeldanomycin (17-AG) using drug concentrations from a few time points.

Methods: Pharmacokinetic data from 34 patients treated at 11 dose levels on a Mayo Clinic Cancer Center phase I clinical trial of 17-AAG was utilized.

Epidermal growth factor receptor variant III status defines clinically distinct subtypes of glioblastoma.

Purpose: The clinical significance of epidermal growth factor receptor variant III (EGFRvIII) expression in glioblastoma multiforme (GBM) and its relationship with other key molecular markers are not clear. We sought to evaluate the clinical significance of GBM subtypes as defined by EGFRvIII status.

Patients And Methods: The expression of EGFRvIII was assessed by immunohistochemistry in 649 patients with newly diagnosed GBM.

Duffy-Santner confidence intervals for the two-stage three-outcome design.

Although the three-outcome phase II clinical trial design (Sargent et al., 2001) has seen increasing use, confidence interval methodology for the binary endpoint had not been explicitly defined. Typical phase II clinical trial designs with binomial endpoints use a sequential binomial confidence interval (SBCI) algorithm (Duffy and Santner, 1987).

Intraoperative electron-beam radiotherapy and ureteral obstruction.

Purpose: To quantify the risk of ureteral obstruction (UO) after intraoperative electron-beam radiotherapy (IOERT).

Methods And Materials: One hundred forty-six patients received IOERT of 7.5 to 30 Gy to 168 ureters; 132 patients received external radiotherapy.

A phase I and pharmacokinetic study of the selective, non-peptidic inhibitor of matrix metalloproteinase BAY 12-9566 in combination with etoposide and carboplatin.

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that degrade the extracellular matrix during the processes of invasion, metastasis and angiogenesis. BAY 12-9566 (BAY) is a selective, non-peptidic biphenyl inhibitor of MMPs, with nanomolar inhibitory activity against MMP-2, -3 and -9, and anti-invasive, anti-metastatic and anti-angiogenic activity in a variety of tumor models. This phase I study of oral BAY was conducted to evaluate the safety and pharmacokinetics of BAY when administered in combination with etoposide (VP-16) or in combination with VP-16 and carboplatin (CBDCA) in subjects with advanced cancer.

A phase I trial of celecoxib in combination with docetaxel and irinotecan in patients with advanced cancer.

Purpose: This phase I study was conducted to determine the safety, tolerability and maximum tolerated dose of the combination of celecoxib, a selective cyclooxygenase-2 inhibitor, with docetaxel and irinotecan, in patients with advanced solid tumors.

Patients And Methods: Patients with solid tumors received one of three escalating dose levels of daily celecoxib in combination with docetaxel and irinotecan administered on days 1 and 8 of an every 21-day cycle. Toxicities were graded by the National Cancer Institute Common Toxicity Criteria (NCI CTC) and recorded as maximum grade per patient for each treatment cycle.

Cognitive function after radiotherapy for supratentorial low-grade glioma: a North Central Cancer Treatment Group prospective study.

Purpose: To evaluate the effects of cranial radiotherapy (RT) on cognitive function in patients with supratentorial low-grade glioma.

Methods And Materials: Twenty adult patients with supratentorial low-grade glioma were treated with 50.4 Gy (10 patients) or 64.

A phase I trial of the novel farnesyl protein transferase inhibitor, BMS-214662, in combination with paclitaxel and carboplatin in patients with advanced cancer.

Purpose: This phase I study was conducted to determine the toxicities, pharmacokinetics, and pharmacodynamics of BMS-214662, a farnesyl transferase inhibitor, in combination with paclitaxel and carboplatin, in patients with advanced solid tumors.

Experimental Design: Patients with solid tumors received one of six escalating dose levels of BMS-214662 infused over 1 hour given following paclitaxel and carboplatin on the first day of a 21-day cycle. Toxicities were graded by the National Cancer Institute common toxicity criteria and recorded as maximum grade per patient for each treatment cycle.

Complementary and alternative medicine use by patients enrolled onto phase I clinical trials.

Purpose: To describe the prevalence, clinical characteristics, and pattern of use of complementary and alternative medicine (CAM) in patients enrolled onto phase I trials.

Patients And Methods: Questionnaires were administered to 108 patients with advanced malignancies enrolled onto phase I chemotherapy trials at the Mayo Clinic Comprehensive Cancer Center (Rochester, MN). CAM was classified into two modalities, pharmacologic and nonpharmacologic.

Immunohistochemical detection of EGFRvIII in high malignancy grade astrocytomas and evaluation of prognostic significance.

The purpose of this study was to establish an accurate and accessible immunohistochemical (IHC) method for detecting vIII Egf receptor and to assess the prognostic significance of the method as applied to the detection of vIII in malignant astrocytomas. The accuracy of the method was determined by comparing vIII immunoreactivity in formalin-fixed and paraffin-embedded tumor sections versus RT-PCR results from the analysis of RNA extracted from corresponding frozen specimens. RT-PCR revealed vIII transcript in 18 of 44 cases in this series, and IHC analysis of matched formalin-fixed and paraffin-embedded sections showed EGFRvIII reactivity in each of these 18 tumors, as well as 1 additional tumor that was negative for vIII transcript.

Prognostic value of proliferation, apoptosis, defective DNA mismatch repair, and p53 overexpression in patients with resected Dukes' B2 or C colon cancer: a North Central Cancer Treatment Group Study.

Purpose: Molecular studies of colon cancer have provided insights into pathogenesis, yet it is unclear how important these markers are in predicting prognosis. This study investigated the prognostic significance of TUNEL, bcl-2, p53, proliferation marker Ki-67 and DNA mismatch repair (MMR) status in patients with Dukes' stage B2 and C colorectal adenocarcinomas.

Patients And Methods: Tumor tissue from 366 patients (75% Dukes' C, 25% Dukes' B2) from four randomized North Central Cancer Treatment Group phase III surgical adjuvant trials were used.