Drug monitoring detects under- and overdosing in patients receiving 5-fluorouracil-containing chemotherapy-results of a prospective, multicenter German observational study.

INTRODUCTION: Body surface area (BSA)-based dosing of 5-fluorouracil (5-FU) results in marked inter-individual variability in drug levels, whereas determination of plasma 5-FU concentration and area under the curve (AUC) is a more precise dosing method but has not been integrated into clinical routine. We conducted a multicenter, prospective study to study 5-FU AUC distributions and assess clinical factors predicting therapeutic dosing in patients receiving BSA-dosed 5-FU. METHODS: Between June 2017 and January 2018, a total of 434 patients receiving continuous, infusional BSA-dosed 5-FU from 37 sites in Germany were included. Plasma 5-FU concentration and AUC were measured in venous blood samples at steady state. The primary objective was to determine 5-FU AUC distributions in relation to the target range, which is defined as 20-30 mg × h/l. The second objective was to explore clinical parameters that correlate with achievement of 5-FU AUC target range. RESULTS: The primary tumor was mainly located in the gastrointestinal tract (96.3%), with colorectal cancer being the most common (71.2%) tumor entity. 5-FU was administered as monotherapy (8.1%) or as part of FOLFOX (33.2%), FOLFIRI (26.3%), or other regimens (12.4%). Treatment setting was adjuvant (31.3%) or metastatic (64.5%). The median AUC was 16 mg × h/l. Only 20.3% of patients received 5-FU treatment within the target range, whereas the majority of patients (60.6%) were underdosed and 19.1% of patients were overdosed. In the univariate logistic regression, treatment setting was the only clinical parameter that significantly correlated with achievement of the target range. Patients treated in the metastatic setting had a 2.1 (95% confidence interval 1.186-3.776, P = 0.011) higher odds to reach the target range compared with patients treated in the adjuvant setting. CONCLUSIONS: The majority of patients received suboptimal doses of 5-FU using BSA dosing. Therapeutic drug monitoring of 5-FU is an option for optimized individualized cancer therapy and should be integrated into the clinical practice.

[Surgical therapy of chronic arterial obstructions of the lower extremities in elderly patients]. / Die chirurgische Therapie des chronischen arteriellen Verschlusses der unteren Extremitäten bei Patienten im hohen Lebensalter.

The aim of this study was to determine whether arterial reconstructions in old age carry an acceptable risk and are reasonable as far as long term results are concerned. The operative mortality was 3,4% for reconstructions distal to the inguinal ligament and 20.5% for reconstructions in the aorto-iliac region. Limb amputations were fraught with a very high mortality of 38.9%.

[Operative treatment of arterial occlusive disease: the risk of operation in high age patients (author's transl)]. / Operative Behandlung der arteriellen Verschlusskrankheit im holen Lebensalter unter Berücksichtigung des Risikos.

Comparative study of 2,168 revascularizations and 221 limb amputations at the surgical hospital of Fürth/Bavaria (1970--1977). The lethality rate after arterial reconstructions in older patients, depending on the type of revascularization, was 3.3 per cent up to 21.1 per cent, being considerably lower than after amputation after which 42.5 per cent of the patients died. Therefore vascular surgery should be considered at an early stage of the disease in older patients with problems of circulation, particularly before any limb amputation.

[Surgical therapy of arterial occlusions. Indication and results of revascularization in 5370 peripheral arteriosclerotic occlusions]. / Chirurgische Therapie arterieller Durchblutungsstörungen. Indikation und Ergebnisse der Revaskularisation bei 5370 peripheren arteriosklerotischen Durchblutungsstörungen.

The results of 5370 revascularizations in peripheral arteriosclerotic occlusive diseases are reported. The operative mortality in 532 carotis interna desobliterations with ischaemia stage II was 2.3%. In stage I of 98 prophylactic operations we lost no patient. Instead of the transthoracic reconstruction we now prefer the extrathoracic bypass because of the lower risk involved. The abdominal aortic aneurysm always is an indication for resection because of the danger of rupture. In cases of 100 operated patients with aneurysm we had a mortality rate in the elective stage of 5.3%, in stage of covered rupture of 47.1% and in ruptured aneurysm 85.7%. The complications in vascular reconstruction of the lower extremity are low. The mortality rate after implantation of aortic bifemoral prosthesis is 3.7%, after an unilateral aortic-femoral prosthesis 2.8% and after all operations below the inguinal ligament 1.0%. Also the femoro-tibial occlusions could be revascularized in bypass-technique with a risk of 1.5% and good early results of 90.3%.