A Simple High-Performance Liquid Chromatography for Determining Lapatinib and Erlotinib in Human Plasma.

BACKGROUND: Lapatinib and erlotinib are used for cancer treatment, showing large interindividual variability. Therapeutic drug monitoring may be useful for assessing the clinical outcomes and adverse events. A simple high-performance liquid chromatography UV method was developed for the determination of lapatinib and erlotinib in human plasma. METHODS: An aliquot of plasma sample spiked with internal standard was treated with acetonitrile to precipitate the proteins. Lapatinib and erlotinib were separated on an octadecylsilyl silica gel column using a mobile phase consisting of acetonitrile, methanol, water, and trifluoroacetic acid (26:26:48:0.1) pumped at a flow rate of 1.0 mL/min. The detection wavelength was set at 316 nm. RESULTS: The calibration curves for lapatinib and erlotinib were linear (r = 0.9999) in the range of 0.125-8.00 mcg/mL. The extraction recoveries for both lapatinib and erlotinib at the plasma concentration of 0.125-8.00 mcg/mL were higher than 89.9% with coefficients of variation less than 3.5%. The coefficients of variation for intraday and interday assays of lapatinib and erlotinib were less than 5.1% and 6.1%, respectively. CONCLUSIONS: The present method can be used for blood concentration monitoring for lapatinib or erlotinib in exactly the same conditions.

Observational study on the efficacy and safety of erlotinib in patients with non-small cell lung cancer.

To evaluate the efficacy and safety of erlotinib for non-small cell lung cancer (NSCLC), we performed a population-based observational study. The study involved 307 patients treated with erlotinib at 14 sites (17 departments) in Ibaraki (Japan) between December 2007 and December 2010. The tumor response and disease control rates were 11.1 and 46.3% in all patients, respectively. The median time to treatment failure and survival time were 1.6 months (95% confidence interval, 41-57 days) and 5.3 months (134-181 days) in all patients, respectively. Survival was significantly prolonged in EGFR mutation-positive patients compared with negative patients. EGFR mutation-negative patients who presented with a skin rash had significantly prolonged survival compared with those without a skin rash. The most common adverse event was skin disorder, followed by diarrhea. Although 45.6% of the patients in this study received erlotinib as a fourth-line or subsequent treatment, the results from this study were similar to those of clinical studies. We deduce that erlotinib is effective against NSCLC and is tolerated in clinical practice.

Erlotinib for elderly patients with non-small-cell lung cancer: Subset analysis from a population-based observational study by the Ibaraki Thoracic Integrative (POSITIVE) Research Group.

The incidence and mortality of lung cancer have increased worldwide over the last decades, with an observed increased incidence particularly among elderly populations. It has not yet been determined whether erlotinib therapy exhibits the same efficacy and safety in elderly and younger patients with non-small-cell lung cancer (NSCLC). The aim of this retrospective subgroup analysis of data from a population-based observational study was to assess the efficacy and safety of erlotinib in an elderly (≥75 years, n=74) and a younger group of patients (<75 years, n=233) who received treatment for NSCLC. The time to treatment failure was similar in the elderly [median, 62 days; 95% confidence interval (95% CI): 44-80 days] compared with the younger group (median, 46 days; 95% CI: 35-53 days) (P=0.2475). The overall survival did not differ between the elderly and younger groups (median, 170 days; 95% CI: 142-239 days vs. median, 146 days; 95% CI: 114-185 days, respectively) (P=0.7642). The adverse events did not differ in incidence between the groups and were manageable, regardless of age. Among the NSCLC patients receiving erlotinib treatment, the outcomes of the elderly (≥75 years) and younger (<75 years) groups of patients were similar in our population-based observational study.

F-18 FDG PET/CT in relapsing polychondritis.

We report a case of relapsing polychondritis for which fluorodeoxyglucose (FDG) positron-emission tomography/computed tomography (PET/CT) showed increased FDG accumulation in all rib cartilages, as well as in the larynx, trachea, and major bronchi. Contrast-enhanced CT during PET/CT showed smooth tracheal and bronchial wall thickening with calcification and airway narrowing. After steroid therapy, clinical symptoms and laboratory data were improved and cartilaginous FDG accumulation had completely disappeared. FDG PET/CT is considered to be a powerful radiological tool to assess the disease activity of relapsing polychondritis.

Usefulness of FDG-PET/CT in the detection of pancreatic metastases from lung cancer.

OBJECTIVE: The objective of this study was to assess the ability to detect pancreatic metastasis of lung cancer and to clarify the degree of fluorodeoxyglucose (FDG) accumulation and computed tomography (CT) characteristics of pancreatic metastasis from lung cancer. METHODS: A total of 573 patients (415 men and 158 women) with lung cancer were retrospectively evaluated. All patients underwent FDG-positron emission tomography (PET)/CT with contrast-enhanced CT for first=stage (313 patients; initial study group) or follow-up study (260 patients; follow-up study group). A lesion was regarded as positive for metastasis on the basis of visual judgment of the degree of increased metabolism by two experienced and independent interpreters, supported by semiquantitative evaluation on the basis of calculation of the maximum standardized uptake value (SUV(max)). RESULTS: Abnormal accumulations in the pancreas were detected in 5 of 313 patients (1.60%) in the initial study group, and 6 of 260 patients (2.31%) in the follow-up study group. Seven of these patients had adenocarcinoma, three had small cell carcinoma, and the rest had large cell endocrine carcinoma. Tumor sizes (longitudinal diameter), measured by CT, of these 11 patients ranged from 6 mm to 52 mm (mean +/- SD 8.3 mm +/- 11.9 mm), and SUV(max) for 1 h ranged from 3.37 to 11.1 (mean +/- SD 6.12 +/- 2.43). Three of these pancreatic lesions were difficult to determine by routine transaxial images, and detection was obvious only by thin-slice images or multiplanar reconstruction images. Contrast-enhanced CT showed gradual fill-in from the peripheral portion to the center. In addition, 10 of 11 cases did not show main pancreatic duct dilatation even if the tumor size was large. CONCLUSIONS: Metastases to the pancreas in lung cancer patients are not so rare and radiologists first have an important role to detect the pancreatic mass and then suggest to metastasis as the likely diagnosis. For this purpose, FDG-PET/CT has an advantage in depicting unsuspected pancreatic metastasis from lung cancer, particularly that which is not detected by CT alone.

[A checking system for injectable anticancer drugs using each patient's own data and its evaluation].

A checking system was developed for risk management of injectable anticancer drug use. Because the dosage and administration of injectable anticancer drugs vary with each patient, checking the prescription and aseptic i.v. admixing can be markedly complicated and time-consuming for pharmacists. The system we investigated in this study provided real-time checking of dosage, drip infusion rate, dosing periods, and dosing-free periods. The prescription parameters for this check included height, weight, body surface area, the medical history of each patient, the patient's ICD10 code' and disease indication from the package insert. Moreover, when preparing for aseptic i.v. admixing, the liquid volume after the anticancer drug has been mixed with other injectable drugs is calculated automatically. The time limits for stability after mixing and clinical laboratory test results are listed on the Work Sheet. As a result, 24 medication errors were prevented in the first 6 months of use of this system. These consisted of over- and under-doses, excessive dosing periods, insufficient dosing-free periods' etc. The time required for preparation of aseptic i.v. admixing decreased by 73% after introducing this system. Because clinical laboratory test results were referenced beforehand, patients to whom the drug should not be administered were recognized in advance. Thus 13 such cases were identified before i.v. admixing. Therefore this system may be useful in terms of rational anticancer drug use and risk management.