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This work was supported by Cancer Research UK (EHW, TJ: C42738/A24868); National Institute of Health Research Cambridge Biomedical Research Centre (HE); National Institute of Health Research UK Academic Clinical Fellowship (CMC); and National Institutes of Health USA Cancer Center support grant (TJ: 5P30CA045508-31). Important oncological management decisions rely on kidney function assessed by serum creatinine-based estimated glomerular filtration rate (eGFR). However, no large-scale multicentre comparison of methods to determine eGFR in patients with cancer are available. To compare the performance of formulas for eGFR based on routine clinical parameters and serum creatinine not calibrated with isotope dilution mass spectrometry (non-IDMS), we studied 3,620 patients with cancer and 166 without cancer who had their GFR measured with an exogenous nuclear tracer at one of seven clinical centres. The mean measured GFR was 86 ml/min. Accuracy of all models was centre-dependent, reflecting inter-centre variability of non-IDMS creatinine measurements. CamGFR was the most accurate model for eGFR (root-mean-squared-error (RMSE) 17.3 ml/min) followed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) model (RMSE 18.2 ml/min).Important oncological management decisions rely on kidney function assessed by serum creatinine-based estimated glomerular filtration rate (eGFR). However, no large-scale multicentre comparison of methods to determine eGFR in patients with cancer are available. To compare the performance of formulas for eGFR based on routine clinical parameters and serum creatinine not calibrated with isotope dilution mass spectrometry (non-IDMS), we studied 3,620 patients with cancer and 166 without cancer who had their GFR measured with an exogenous nuclear tracer at one of seven clinical centres. The mean measured GFR was 86 ml/min. Accuracy of all models was centre-dependent, reflecting inter-centre variability of non-IDMS creatinine measurements. CamGFR was the most accurate model for eGFR (root-mean-squared-error (RMSE) 17.3 ml/min) followed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) model (RMSE 18.2 ml/min).Important oncological management decisions rely on kidney function assessed by serum creatinine–based estimated glomerular filtration rate (eGFR). However, no large-scale multicenter comparisons of methods to determine eGFR in patients with cancer are available. To compare the performance of formulas for eGFR based on routine clinical parameters and serum creatinine not calibrated with isotope dilution mass spectrometry, we studied 3620 patients with cancer and 166 without cancer who had their glomerular filtration rate (GFR) measured with an exogenous nuclear tracer at one of seven clinical centers. The mean measured GFR was 86 mL/min. Accuracy of all models was center dependent, reflecting intercenter variability of isotope dilution mass spectrometry–creatinine measurements. CamGFR was the most accurate model for eGFR (root-mean-squared error 17.3 mL/min) followed by the Chronic Kidney Disease Epidemiology Collaboration model (root-mean-squared error 18.2 mL/min). Publisher PDF

BACKGROUND Ongoing clinical trials are addressing the accuracy and safety of sentinel node biopsy (SNB) in the treatment of breast cancer; however, SNB is already increasingly being used in clinical practice. This study examined the extent and time trends of the use of SNB in stage I and II breast cancer patients. METHODS Clinical data were collected from stage I and II (tumor size < or =5.0 cm) breast cancer patients (n = 3003) who were treated at five comprehensive cancer centers between July 1, 1997, and December 31, 2000. Axillary surgery was classified as SNB alone, SNB + axillary node dissection (AND), AND alone, or none. Patterns of use of axillary surgery were summarized as the percentage of patients receiving each surgery type. The statistical significance of time trends for the use of SNB alone was analyzed by logistic regression models. All statistical tests were two-sided. RESULTS Overall, SNB alone was used in 13% of patients, SNB + AND in 22%, AND alone in 59%, and no axillary surgery in 6%. Use of SNB alone was statistically significantly associated with breast-conserving surgery of both smaller (< or =2 cm) and larger tumors (2-5 cm) (P

Patients with epithelial ovarian cancer are often diagnosed with advanced-stage disease. Although clinical complete remissions are obtained in the majority of patients through a combination of cytoreductive surgery and chemotherapy, relapse is common. A number of agents with diverse biologic mechanisms have been identified with activity in the setting of recurrent disease. Strategies for management of patients with recurrent disease, including classification, treatment goals, and therapeutic options will be reviewed.

Although the combination of platinum and paclitaxel offers effective chemotherapy for advanced ovarian cancer, the majority of women will eventually relapse with development of drug-resistant disease. Topotecan is the most extensively studied agent currently available for management of recurrent ovarian cancer and has been approved by the FDA for that particular indication. Early use of topotecan offers an effective and tolerable strategy that can prolong the platinum-free interval and optimize subsequent retreatment with platinum.

Single-chain Fv fusions with C-terminal cysteinyl peptides (sFv') have been engineered using model sFv proteins based upon the 26-10 anti-digoxin IgG and 741F8 anti-c-erbB-2 IgG monoclonal antibodies. As part of the 741F8 sFv construction process, the PCR-amplified 741F8 VH gene was modified in an effort to correct possible primer-induced errors. Genetic replacement of the N-terminal beta-strand sequence of 741F8 VH with that from the FR1 of anti-c-erbB-2 520C9 VH resulted in a dramatic improvement of sFv folding yields. Folding in urea-glutathione redox buffers produced active sFv' with a protected C-terminal sulfhydryl, presumably as the mixed disulfide with glutathione. Disulfide-bonded (sFv')2 homodimers were made by disulfide interchange or oxidation after reductive elimination of the blocking group. Both 26-10 (sFv')2 and 741F8 (sFv')2 existed as stable dimers that were well behaved in solution, whereas 741F8 sFv and sFv' exhibited considerable self-association. The 741F8 sFv binds to the extracellular domain (ECD) of the c-erbB-2 oncogene protein, which is often overexpressed in breast cancer and other adenocarcinomas. The recombinant ECD was prepared to facilitate the analysis of 741F8 binding site properties; the cloned ECD gene, modified to encode a C-terminal Ser-Gly-His6 peptide, was transfected into Chinese hamster ovary cells using a vector that also expressed dihydrofolate reductase to facilitate methotrexate amplification. Optimized cell lines expressed ECD-His6 at high levels in a cell bioreactor; after isolation by immobilized metal affinity chromatography, final ECD yields were as high as 47 mg/l. An animal tumor model complemented physicochemical studies of 741F8 species and indicated increased tumor localization of the targeted 741F8 (sFv')2 over other monovalent 741F8 species.

Lymphokine-activated killer (LAK) cells and interleukin-2 (IL-2) were administered by the ip route to patients with intra-abdominal malignancies. Pharmacokinetic studies of IL-2 revealed 10- to 100-fold higher concentrations of IL-2 in peritoneal fluid versus serum. Ip levels of IL-2 were maintained well above those required to generate and maintain LAK cells in vitro. LAK cell activity was detectable in the peritoneal fluid for the duration of each treatment cycle and did not disappear until IL-2 was discontinued. Detection of interferon-gamma (IFN-gamma) in the peritoneal fluid of all patients was consistent with production in situ by activated lymphocytes. In some patients, low but detectable levels of IFN-gamma were also found in the serum. In vivo activation of monocytes in the peritoneal fluid as measured by in vitro production of hydrogen peroxide was documented in the majority of patients. Neither interleukin-1 nor tumor necrosis factor-alpha was detected in the peritoneal fluid. We found no correlation between the presence or levels of IL-2, IFN-gamma, or LAK cell lytic activity in peritoneal fluid or serum and response or nonresponse to therapy.