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.

[The value of hormonal and sonographic parameters in the diagnosis of disordered and normal early pregnancy]. / Wertigkeit hormoneller und sonographischer Parameter bei der Diagnostik der gestörten bzw. ungestörten Frühgravidität.

In 112 clinical pregnancies after IVF/ET or GIFT, the importance of beta-HCG progesterone and 17 beta-estradiol was evaluated. Additionally, we performed a vaginosonography to confirm an early intrauterine pregnancy. The aim of the study was to define, when a clinical pregnancy can be detected as early as possible and when the differential diagnosis of intact or abnormal pregnancy can be made. By measuring E2 in an HCG substituted cycle, the diagnosis of a clinical pregnancy is possible as soon as day +12 after induction of ovulation. When considering beta-HCG levels alone, the same diagnosis can be made at day +18. Single determinations of HCG level do not offer a satisfactory diagnosis, because of intra-individual variations. A progesterone drop always demonstrates a disturbed early pregnancy. Using a combination of hormonal serial measurements of HCG, E2, progesterone and vaginosonography, the diagnosis of an intact intrauterine pregnancy should be possible as early as day +27 after ovulation induction.

Acute myelogenous leukaemia and myelomonocytic blast crisis following polycythemia vera in HIV positive patients: report of cases and review of the literature.

BACKGROUND: Acute myelogenous leukaemia (AML) and myeloproliferative diseases are rare in HIV-infected individuals and optimal treatment has not been defined. PATIENTS AND METHODS: We report on the cases of two HIV-infected men, one with AML and one with myeloid blast crisis after polycythaemia vera (PV). A comprehensive review of the available literature will be presented. RESULTS: Patient 1, a 57-year-old bisexual man known to be HIV seropositive for more than four years (CDC-category A1), presented with a pulmonary infiltrate. On admission WBC showed leukocytes 5.6 x 10(9)/l and the differential revealed 80% blasts. A diagnosis of AML FAB M0 was made. Pneumonia resolved under antibiotic treatment and the patient received induction chemotherapy. However, he once more developed multiple pulmonary infiltrates and died of respiratory failure despite broad spectrum antibiotic and antimycotic therapy. Autopsy revealed pulmonary aspergillosis. Patient 2 was a 63-year old HIV-positive hemophiliac (CDC A3) with a 10-year history of PV. On admission his white cell count showed leukocytes 256.6 x 10(9)/l with 82% blasts. Cytochemistry revealed myelomonocytic differentiation. The patient died of tumor lysis syndrome with renal and cardio-pulmonary failure two days later. CONCLUSIONS: This is the first report of an HIV-infected individual with AML M0. The literature describes the cases of 39 HIV+ patients with AML and only one further case with PV. The association of both, myeloproliferative disease and AML with HIV infection is coincidental. However, the proportion of FAB type M4/5 appears to be higher than in the general population. Despite a high risk of treatment associated mortality durable remissions can be achieved in a small proportion of HIV-infected patients with AML.