Biomedical subjects

Sjoerd Rodenhuis

Publications and source records attributed to Sjoerd Rodenhuis.

22 records · Page 2Linked to original sources

PubMed2003

Sorption of thiotepa to polyurethane catheter causes falsely elevated plasma levels.

Central venous access catheters are commonly used in clinical oncology. The double lumen variant is applied in pharmacokinetic studies for simultaneous administration and blood sampling when frequent blood collections are necessary. Occlusion of one lumen, a common complication, necessitates the investigator perform blood sampling through the administration lumen after interrupting the infusion. Plasma concentrations measured in this sample can be influenced by sorption of the previously infused compound to the catheter lumen. In this study, the quality of cyclophosphamide, thiotepa, and carboplatin plasma concentrations is investigated when sampling is performed through the administration lumen.

Absorption↗

PubMed2002

A gene-expression signature as a predictor of survival in breast cancer.

BACKGROUND: A more accurate means of prognostication in breast cancer will improve the selection of patients for adjuvant systemic therapy. METHODS: Using microarray analysis to evaluate our previously established 70-gene prognosis profile, we classified a series of 295 consecutive patients with primary breast carcinomas as having a gene-expression signature associated with either a poor prognosis or a good prognosis. All patients had stage I or II breast cancer and were younger than 53 years old; 151 had lymph-node-negative disease, and 144 had lymph-node-positive disease. We evaluated the predictive power of the prognosis profile using univariable and multivariable statistical analyses. RESULTS: Among the 295 patients, 180 had a poor-prognosis signature and 115 had a good-prognosis signature, and the mean (+/-SE) overall 10-year survival rates were 54.6+/-4.4 percent and 94.5+/-2.6 percent, respectively. At 10 years, the probability of remaining free of distant metastases was 50.6+/-4.5 percent in the group with a poor-prognosis signature and 85.2+/-4.3 percent in the group with a good-prognosis signature. The estimated hazard ratio for distant metastases in the group with a poor-prognosis signature, as compared with the group with the good-prognosis signature, was 5.1 (95 percent confidence interval, 2.9 to 9.0; P<0.001). This ratio remained significant when the groups were analyzed according to lymph-node status. Multivariable Cox regression analysis showed that the prognosis profile was a strong independent factor in predicting disease outcome. CONCLUSIONS: The gene-expression profile we studied is a more powerful predictor of the outcome of disease in young patients with breast cancer than standard systems based on clinical and histologic criteria.

Adult↗

PubMed2002

Extremely high exposures in an obese patient receiving high-dose cyclophosphamide, thiotepa and carboplatin.

An obese 53-year-old woman (height 167 cm, weight 130 kg) with metastatic breast cancer received high-dose chemotherapy comprising cyclophosphamide, thiotepa and carboplatin (CTC). The cyclophosphamide (1 g/m(2) per day) and thiotepa (80 mg/m(2) per day) doses were based on body surface area (BSA) calculated using total body weight (TBW). The daily carboplatin dose was calculated based on the Calvert formula, using a target area under the plasma concentration-time curve (AUC) value of 3.25 mg.min/ml and applying the Cockcroft-Gault equation to estimate the glomerular filtration rate. The patient received the three agents as short infusions over four consecutive days. For therapeutic drug monitoring (TDM), blood samples were collected on day 1. Thiotepa and its main metabolite tepa, ultrafilterable platinum, cyclophosphamide and its activated metabolite 4-hydroxycyclophosphamide were determined. Individual pharmacokinetics were assessed using Bayesian analysis. Exposure to the individual compounds was determined by calculating the AUC. Exposures to 4-hydroxycyclophosphamide, the combination of thiotepa/tepa and carboplatin were 94%, 117% and 71% higher than the median respective exposures in a non-obese population of patients ( n=24) receiving similar doses. Because high AUCs of 4-hydroxycyclophosphamide, thiotepa/tepa and carboplatin correlate with increased toxicity, the treatment risk in this obese patient was significantly increased. Therefore doses were adapted on the 3rd day of the course. It is concluded that cyclophosphamide and thiotepa in obese patients should not be dosed on the basis of BSA incorporating TBW since the patient will be overexposed. Moreover, applying the Cockcroft-Gault equation to obese patients leads to an overprediction of creatinine clearance and, when used in the Calvert equation, consequently to a carboplatin dose that is too high. Obese patients represent a unique group of patients in which TDM is extremely valuable in optimizing dosing, particularly in high-dose chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2002

Detection of circulating breast tumor cells by differential expression of marker genes.

PURPOSE: We undertook a systematic approach to identify breast cancer (BC) marker genes with molecular assays and evaluated these marker genes for the detection of minimal residual disease in peripheral blood mononuclear cells (PBMCs). EXPERIMENTAL DESIGN: We used serial analysis of gene expression to identify a range of genes that were expressed in BC but absent in the expression profiles of blood and bone marrow cells. Next, we evaluated a panel of four marker genes (p1B, PS2, CK19, and EGP2) by real-time quantitative PCR in 103 PBMC samples from patients with metastatic BC (stage III/IV) and in 96 PBMC samples from healthy females. RESULTS: Increased marker gene expression of at least one marker was seen in 33 of 103 patients. Using quadratic discriminant analysis including all four marker genes, we determined a discriminant value with 29% positivity in the BC patient group that did not yield false positive results among the healthy females. CONCLUSIONS: Real-time PCR for the simultaneous expression of multiple cancer-specific genes may ensure the specificity required for the clinical application of mRNA expression-based assays for occult tumor cells.

Antigens, Neoplasm↗