Biomedical subjects

M Royce

Publications and source records attributed to M Royce.

3 recordsLinked to original sources

PubMed2004

Gene expression profiles predict complete pathologic response to neoadjuvant paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide chemotherapy in breast cancer.

PURPOSE: The goal of this study was to examine the feasibility of developing a multigene predictor of pathologic complete response (pCR) to sequential weekly paclitaxel and fluorouracil + doxorubicin + cyclophosphamide (T/FAC) neoadjuvant chemotherapy regimen for breast cancer. PATIENTS AND METHODS: All patients underwent one-time pretreatment fine-needle aspiration to obtain RNA from the cancer for transcriptional profiling using cDNA arrays containing 30721 human sequence clones. Analysis was performed after profiling, and 42 patients' clinical results were available, 24 of which were used for predictive marker discovery; 18 patients' results were used as an independent validation set. RESULTS: Thirty-one percent of patients had pCR (six discovery and seven validation), defined as disappearance of all invasive cancer in the breast after completion of chemotherapy. We could identify no single marker that was sufficiently associated with pCR to be used as an individual predictor. A multigene model with 74 markers (P <or=.09) was built using data from the discovery samples and tested on the validation samples. Overall, a 78% (14 of 18) predictive accuracy was observed, with a 100% (three of three) positive predictive value for pCR, a 73% (11 of 15) negative predictive value, a sensitivity of 43% (three of seven), and a specificity of 100% (11 of 11). The expected response rate to T/FAC neoadjuvant therapy in unselected patients is 28%. CONCLUSION: Our results suggest that transcriptional profiling has the potential to identify a gene expression pattern in breast cancer that may lead to clinically useful predictors of pCR to T/FAC neoadjuvant therapy.

Adult↗

PubMed1999

Oral fluoropoyrimidines.

Protracted intravenous infusions of fluorouracil (5-FU) in the treatment of colorectal cancer have been associated with a reduction in toxicity and enhanced clinical activity compared with bolus 5-FU schedules. However, these protracted infusions require portable infusion pumps and central venous lines, which are associated with complications of venous thrombosis, infection, and line slippage. An effective oral 5-FU formulation could provide a more convenient protracted treatment method with fewer complications. Because of its inconsistent and erratic absorption, the use of oral 5-FU was abandoned decades ago. The inconsistent absorption of oral 5-FU may be attributed to varying levels of dihydropyrimidine dehydrogenase (DPD) in the gastrointestinal tract. Two methods have been used to circumvent 5-FU's metabolism by DPD in the gastrointestinal tract. First, DPD may be inactivated, allowing for reliable, consistent absorption of 5-FU. Second, 5-FU prodrugs can be administered, being absorbed as intact molecules via the gastrointestinal tract and subsequently converted to 5-FU. The oral fluoropyrimidines discussed here are capable of providing prolonged 5-FU exposure with a reduced incidence of toxicity.

Animals↗

PubMed1998

The oral fluorouracil prodrugs.

Discussed herein are selected oral fluorinated pyrimidines that are converted to 5-fluorouracil (5-FU) in vivo to exert antitumor activity. These agents include capecitabine (Xeloda), tegafur-uracil (UFT) plus leucovorin (Orzel), and S-1 (BMS247616). These agents offer the convenience of an orally administered therapy with potentially fewer toxic effects than conventional bolus regimens of 5-FU plus leucovorin. These oral agents provide prolonged 5-FU exposure at lower peak concentrations than observed with bolus intravenous administration of 5-FU and may confer pharmacoeconomic advantages by reducing administration costs and toxicity-related hospitalizations. These regimens also have the potential for improved therapeutic activity by achieving higher 5-FU concentrations in the tumor or by biochemically modulating 5-FU. Phase III trials in patients with advanced colorectal carcinomas are comparing the antitumor activity of these agents with that of intravenous 5-FU plus leucovorin.

Administration, Oral↗