Prospective, Multicenter Study of 5-Fluorouracil Therapeutic Drug Monitoring in Metastatic Colorectal Cancer Treated in Routine Clinical Practice.

BACKGROUND: Studies have demonstrated that body surface area-based dosing of chemotherapy drugs leads to significant individual exposure variability, with a substantial risk of under- or overdosing. The present study was initiated to validate the use of therapeutic drug management (TDM) to personalize 5-fluorouracil (5-FU) dosing in patients with metastatic colorectal cancer treated in routine clinical practice. PATIENTS AND METHODS: A total of 75 patients with metastatic colorectal cancer from 8 German medical centers received ≤ 6 administrations of infusional 5-FU according to the AIO (folinate, 5-FU; n = 16), FOLFOX6 (leucovorin calcium [folinic acid], 5-FU, and oxaliplatin; n = 26), or FUFOX (oxaliplatin plus 5-FU/folinic acid; n = 33) regimen. Initial infusional 5-FU dosing for all patients was determined by the BSA. Individual 5-FU exposure (area under the curve [AUC]) was measured using an immunoassay of a blood sample taken during each infusion. To achieve a target AUC of 20 to 30 mg × h/L, subsequent infusional 5-FU doses were adjusted according to the previous cycle's 5-FU AUC. The primary objective was to confirm that TDM of infusional 5-FU resulted in an increased proportion of patients in the target AUC range at the fourth versus the first administration. The secondary objective was to determine whether 5-FU TDM reduced the treatment-related toxicities compared with the historical data. RESULTS: The average 5-FU AUC at the first administration was 18 ± 6 mg × h/L, with 64%, 33%, and 3% of the patients below, within, or above the target AUC range, respectively. By the fourth administration, the average 5-FU AUC was 25 ± 7 mg × h/L (P < .001), with 54% of patients within the target 5-FU AUC range (P = .0294). The incidence of 5-FU-related grade 3 and 4 diarrhea (4.6%), nausea (3.4%), fatigue (0.0%), and mucositis (0.2%) was reduced compared with the historical data, despite 55% of the patients receiving increased doses. CONCLUSION: Personalization of 5-FU dosing using TDM in routine clinical practice resulted in significantly improved 5-FU exposure and suggested a lower incidence of 5-FU-related toxicities.

Comparison of the vasodilating effect of nitroglycerin, verapamil, and tolazoline in hand angiography.

PURPOSE: To compare the vasodilating effect and safety of intraarterial verapamil with the long-accepted standard vasodilators nitroglycerin and tolazoline in hand angiography. MATERIALS AND METHODS: The authors studied 25 patients who underwent brachial artery angiography. In 22 cases, there was poor or moderate visualization of the forearm and hand vasculature. To improve blood flow to the periphery, subsequent angiograms with intraarterial vasodilating agents were obtained. First, nitroglycerin was administered (n = 22). In cases of continuous poor or moderate visualization of the forearm and hand vasculature, another angiogram was obtained with verapamil (n = 21). If opacification remained poor or moderate, eventually tolazoline was injected (n = 20). To avoid pharmacologic interactions of the different vasodilating drugs, a minimum 15-minute interval between series was observed. The degree of opacification of the forearm and hand arteries was graded on a scale from 1 to 5: visualization of the forearm arteries only was defined as 1, of the forearm arteries and superficial/deep palmar arch as 2, of the forearm arteries, superficial/deep palmar arch, and digital arteries to the level of the metacarpophalangeal joints as 3, to the level of the proximal interphalangeal joints as 4, and to the distal interphalangeal joints as 5. RESULTS: All three vasodilating agents demonstrated highly significant improvement in blood flow; verapamil and tolazoline showed statistically greater effects than nitroglycerin. Verapamil caused the fewest and least severe adverse effects. CONCLUSION: Intraarterial verapamil and tolazoline are comparable in terms of vasodilatory efficacy in hand arteries. However, because of its favorable adverse effect profile, verapamil is recommended for optimizing visualization of the peripheral arterial vascular system.