Real-World Adverse Effects of Capecitabine Toxicity in an Elderly Population.

BACKGROUND: Few studies have assessed the safety and effectiveness of the numerous available chemotherapeutic therapies for geriatric oncology patients. Most safety studies are conducted in large trials, and there is some uncertainty surrounding whether the results would be the same in typical daily use. OBJECTIVE: This retrospective study aims to assess the adverse effects of real-world capecitabine use in elderly patients. METHODS: We reviewed the records of patients treated with capecitabine in an oncology department of a University Clinic in Nijmegen, The Netherlands. We scored adverse effects such as hand-foot syndrome and diarrhea, and dosage adjustments and the reasons for them. In total, 132 patients were included, 69 of whom were aged 70 years or below (mean age: 57 years), while 63 were aged older than 70 years (mean age: 74 years). RESULTS: Patients aged over 70 years experienced more serious adverse effects than younger patients. Grade 2 or 3 hand-foot syndrome toxicity was experienced by 20.2% of patients aged younger than 70 years and by 34.9% of patients older than 70 years (p = 0.059). Grade 2, 3, or 4 diarrhea was experienced by 17.4% of the patients aged younger than 70 years but by 31.7% of the patients aged older than 70 years (p = 0.044). Dosage was adjusted for 27/69 patients in the younger group and 52/63 patients in the older group (p = 0.001). CONCLUSION: The difference in observed adverse effects cannot be the sole explanation for the high incidence of observed dose adjustments. A prospective follow-up study of elderly patients using capecitabine outside clinical trials is needed to evaluate the optimum balance between adverse effects and efficacy.

Pharmacokinetic Drug-Drug Interaction Study Between Raltegravir and Atorvastatin 20 mg in Healthy Volunteers.

BACKGROUND: Dyslipidemia is highly prevalent among patients with HIV infection and contributes to an increased risk of cardiovascular disease. We investigated the influence of a frequently used statin, atorvastatin, on the pharmacokinetics of the HIV-integrase inhibitor raltegravir and vice versa. METHODS: Open-label, crossover 3-period phase I trial in 24 healthy volunteers. Subjects took raltegravir 400 mg two times a day for 7 days, atorvastatin 20 mg once a day for 7 days, and the combination of atorvastatin 20 mg once a day + raltegravir 400 mg two times a day for 7 days with 2-week washout periods in between. Intensive steady-state 12- and 24-hour pharmacokinetic blood sampling was performed. Geometric mean ratios of the test treatment (combination raltegravir + atorvastatin) versus the reference treatment (raltegravir or atorvastatin alone) and 90% confidence intervals were calculated for the area under the plasma concentration-time curve (AUC). Fasting lipid profiles were obtained to assess short-term lipid-lowering effect of atorvastatin with or without concomitant raltegravir use. RESULTS: Twenty-four healthy volunteers (11 males) were enrolled. All but 1 subject completed the trial, and no serious adverse events were reported. Geometric mean ratios (90% confidence interval) were 1.01 (0.68-1.51) for raltegravir AUC(0-12h) and 1.00 (0.90-1.11) for atorvastatin AUC(0-24h). The AUC(0-24h) metabolite-to-parent ratio for atorvastatin lactone, ortho-hydroxy, and para-hydroxy atorvastatin did not change during concomitant raltegravir use. The effect of atorvastatin on low-density lipoprotein cholesterol was not significantly different when combined with raltegravir versus atorvastatin alone (P = 0.638). CONCLUSIONS: Atorvastatin 20 mg has no clinically relevant effect on the pharmacokinetics of raltegravir and vice versa. The combination was well tolerated and can be administered without dose adjustments.

A novel fluorescent imaging agent for diffuse optical tomography of the breast: first clinical experience in patients.

PURPOSE: This is the first clinical evaluation of a novel fluorescent imaging agent (Omocianine) for breast cancer detection with diffuse optical tomography (DOT). PROCEDURES: Eleven women suspected of breast cancer were imaged with DOT at multiple time points (up to 24 h) after receiving an intravenous injection of Omocianine (doses 0.01 to 0.1 mg/kg bodyweight). Breast MRI was obtained for comparison. RESULTS: Histopathology showed invasive cancer in ten patients and fibroadenoma in one patient. With the lowest dose of Omocianine, two of three lesions were detected; with the second dose, three of three lesions were detected; with the two highest doses, none of five lesions were detected. Lesion location on DOT showed excellent agreement with MRI. Optimal lesion-to-background signals were obtained after 8 h. No adverse events occurred. CONCLUSIONS: Lowest doses of Omocianine performed best in lesion detection; DOT using a low-dose fluorescent agent is feasible and safe for breast cancer visualization in patients.

Linear image reconstruction for a diffuse optical mammography system in a noncompressed geometry using scattering fluid.

Diffuse optical tomography (DOT) is a potential new imaging modality to detect or monitor breast lesions. Recently, Philips developed a new DOT system capable of transmission and fluorescence imaging, where the investigated breast is hanging freely into the measurement cup containing scattering fluid. We present a fast and robust image reconstruction algorithm that is used for the transmission measurements. The algorithm is based on the Rytov approximation. We show that this algorithm can be used over a wide range of tissue optical properties if the reconstruction is adapted to each patient. We use estimates of the breast shape and average tissue optical properties to initialize the reconstruction, which improves the image quality significantly. We demonstrate the capability of the measurement system and reconstruction to image breast lesions by clinical examples.

Diffuse optical tomography of the breast: preliminary findings of a new prototype and comparison with magnetic resonance imaging.

This paper presents an evaluation of a prototype diffuse optical tomography (DOT) system. Seventeen women with 18 breast lesions (10 invasive carcinomas, 2 fibroadenomas, and 6 benign cysts; diameters 13-54 mm) were evaluated with DOT and magnetic resonance imaging (MRI). A substantial fraction of the original 36 recruited patients could not be examined using this prototype due to technical problems. A region of interest (ROI) was drawn at the lesion position as derived from MRI and at the mirror image site in the contralateral healthy breast. ROIs were assessed quantitatively and qualitatively by two observers independently in two separate readings. Intra- and interobserver agreements were calculated using kappa statistics (k) and intraclass correlation coefficients (ICCs). Discriminatory values for presence of malignancy were determined by receiver operating characteristic (ROC) analyses. Intraobserver agreements were excellent (k 0.88 and 0.88; ICC 0.978 and 0.987), interobserver agreements were good to excellent (k 0.77-0.95; ICC 0.96-0.98). Discriminatory values for presence of malignancy were 0.92-0.93 and 0.97-0.99 for quantitative and qualitative ROC analysis, respectively. This DOT system has the potential to discriminate malignant from benign breast tissue in a reproducible qualitative and quantitative manner. Important technical improvements are required before this technique is ready for clinical application.